Category: Diet

Role of free radicals

Role of free radicals

Role of free radicals Letters. Platelets involved in wound repair and blood homeostasis Bone strength improvement ROS to recruit additional frfe to radlcals of injury. Hyperglycemia induces the generation fred superoxide ions in endothelial Role of free radicals at the mitochondrial level. Antioxidants and Cancer Prevention On This Page What are free radicals, and do they play a role in cancer development? From the Edited Volume Phytochemicals - Source of Antioxidants and Role in Disease Prevention Edited by Toshiki Asao and Md Asaduzzaman Book Details Order Print. Free radicals and antioxidants in normal physiological functions and human disease.

Role of free radicals -

These reactions are called oxidation. They can be beneficial or harmful. Antioxidants are molecules that can donate an electron to a free radical without making themselves unstable. This causes the free radical to stabilize and become less reactive. Read on to learn how oxidative stress affects the body and how to manage and prevent this imbalance.

Oxidation is a normal and necessary process that takes place in your body. When functioning properly, free radicals can help fight off pathogens. Pathogens lead to infections. When there are more free radicals present than can be kept in balance by antioxidants, the free radicals can start doing damage to fatty tissue, DNA, and proteins in your body.

Proteins, lipids, and DNA make up a large part of your body, so that damage can lead to a vast number of diseases over time. These include:. Everyone produces some free radicals naturally in their body through processes like exercise or inflammation.

However, there are things you can do to minimize the effects of oxidative stress on your body. The main thing you can do is to increase your levels of antioxidants and decrease your formation of free radicals. Eating five servings per day of a variety of fruits and vegetables is the best way to provide your body what it needs to produce antioxidants.

Examples of fruits and vegetables include:. Other healthy lifestyle choices can also prevent or reduce oxidative stress. Here are some lifestyle choices that will help:. Oxidative stress can cause damage to many of your tissues, which can lead to a number of diseases over time.

Our experts continually monitor the health and wellness space, and we update our articles when new information becomes available. Brain fog is a symptom of another medical condition. Once the cellular antioxidant system is disrupted and becomes deficient, oxidative stress emerges thereby promoting several diseases such as diabetes, arthrosclerosis, cancer, cardiovascular diseases, etc.

Because of their natural origin and therapeutic benefits, plants have been considered as a major source of antioxidants. Certain non-enzymatic plant phytochemicals such as glutathione, polyphenols, bioflavonoids, carotenoids, hydroxycinnamates as well as some vitamins have shown to possess antioxidant properties in vitro and in vivo.

These plant phytochemicals are now been used in the prevention and management of oxidative stress-related diseases. Man as a living creature has always indulged himself into several activities to ensure his survival and well-being.

In so doing, he has induced the production or release of various reactive substances or free radicals which are either consumed or inhaled. Also, certain physiological processes in the body generate free radicals or proxidants.

These free radicals or reactive species, because of their deficiency in electron and instability, attack electron rich centers such as lipid membranes, proteins and nucleic acids thereby damaging cells and tissues in the body.

Eventual, the human body is adapted to remove these unstable molecules by a myriad of molecules including certain enzymes collectively known as antioxidants.

This antioxidant defense system reduces the level of these free radicals in the body and maintains the homeostatic balance for proper functioning of the body.

However, when these reactive species are overwhelming high in the body, it surpasses the capacity of the antioxidant defense system leading to a condition known as oxidative stress.

This imbalance between antioxidant and proxidants is characteristic of certain disease conditions such as diabetes, atherosclerosis, cardiovascular diseases, cancer etc. One of the possible remedy for this condition is to supplement the endogenous antioxidant defense system with exogenous antioxidants.

Plants have gained considerable interest in recent time in managing oxidative stress related diseases; firstly, because of their ethnopharmacological uses in managing diseases and secondly, due to their richness in phytochemicals which possess antioxidant properties.

Hence, this chapter is aimed to give an overview of free radicals, their sources of origin and processes of generation in the environment and body. Also, it will highlight on the various mechanisms of free radical induced cellular damage and the associated diseases due to oxidative stress.

The various mechanisms of the antioxidant defense system; both enzymatic and non-enzymatic antioxidants will be described as well as the contribution of plant phytochemicals as antioxidants. Emphasis will be laid on some plants and phytochemicals with antioxidant activities stating their mode of scavenging free radicals and prevention of oxidative stress-related diseases.

Free radicals are molecular species with unpaired electrons in their atomic orbital capable of independent existence. As such, these radicals are highly reactive and can either extract an electron from molecules or donate an electron to other molecules thus acting as a reductant or an oxidant.

Some oxygen species known as reactive oxygen species ROS are non-reactive in their natural state but are capable of generating free radicals. The idea of free radicals began in chemistry around the beginning of the twentieth century, where chemists initially described them as intermediate organic and inorganic compounds with several suggested definitions.

A clear understand of these radicals was then proposed based on the work of Daniel Gilbert and Rebecca Gersham in [ 2 ] in which these radicals were suggested to play important roles in biological environments but also responsible for certain deleterious processes in the cell.

Thereafter by , Herman Denham further suggested that these reactive species may play critical roles in physiological process particularly aging process [ 3 ].

This hypothesis on the theory of free-radical on aging, inspired numerous research and studies which significantly contributed to the understanding of radicals and other related species such as ROS, reactive nitrogen species RNS and non-radical reactive species [ 4 ].

ROS are classified into two major categories of compounds which includes the free radicals and the non-reactive radicals. These species are considered as free radicals since they contain at least one unpaired electron in the shells around the atomic nucleus which makes them unstable and therefore can easily donate or obtain another electron to attain stability.

As such, they are highly reactive and capable of independent existence [ 6 , 7 ]. On the other hand, the non-reactive radicals are a group of compounds which are not radicals but are extremely reactive or can easily be converted to reactive species.

Examples of these substances include hypochlorous acid HClO , hydrogen peroxide H 2 O 2 , organic peroxides, aldehydes, ozone O 3 , and O 2 as shown in Table 1. As reviewed from Sultan [ 8 ], free radicals can originate either from the environment, physiological processes or endogenous sources.

External sources: Certain organic compounds in the atmosphere can react non-enzymatically with oxygen to generate free radicals.

Also, reactions initiated by ionizing radiations in the environment can generate free radicals. Thus, some external sources of free radicals include environmental pollutant, cigarette smoke, alcohol, radiations, ozone, ultraviolet light, pesticides, anesthetic, certain drugs, industrial solvents etc.

Endogenous sources: This includes processes in living organisms that necessitates enzymatic reactions to generate free radicals. These include reactions involved in the respiratory chain, cytochrome P system, phagocytosis and prostaglandin synthesis.

Some of these endogenous sources of free radicals generation include reactions in the mitochondria, phagocytes, inflammation, arachidonate pathways, etc. Also, reactions involving iron and other transition metals, peroxisomes, xanthine oxidase, etc.

are also endogenous sources of free radicals. Physiological sources: Certain physiological state or processes like stress, emotion, aging, etc. mental status and disease conditions are also responsible for the formation of free radicals. For example, hyperglycemia is a major source of free radicals in diabetes patients through various metabolic pathways which include increase flux of glucose through the polyol pathway, increase formation of advanced glycation end-products AGEs and activation of their receptors, activation of protein kinase C PKC isoforms, activation of overactivity of hexosamine pathway and decrease antioxidant defense [ 9 ].

Free radicals are generated through various physiological processes in living organisms. Once generated, they can react with other biomolecules to attain stability. In living systems, superoxide can be generated through several mechanisms [ 10 ].

Several molecules such as flavine nucleotides, adrenaline, thiol compounds, glucose, etc. can be oxidized in the presence of oxygen to generate superoxide and these reactions are greatly accelerated by the presence of transition metals such as iron or copper. During the electron transport chain in the inner mitochondrial membrane, oxygen is reduced to water thereby producing free radical intermediates that subsequently reacts with free electrons to produce superoxide [ 11 ].

Certain reactions by enzymes such as cytochrome p oxidase in the liver releases free electrons that can react with oxygen to produce superoxide. Other enzymes can neutralize nitric oxide thereby producing superoxide [ 12 ]. Also, phagocytic cells during respiratory burst can generate superoxide [ 13 ].

Hydrogen peroxide H 2 O 2 : Hydrogen peroxide is mostly produced from the spontaneous dismutation reaction of superoxide in biological systems. Also, several enzymatic reactions including those catalyzed by D-amino acid and glycolate oxidases can directly produce H 2 O 2 [ 14 ].

Generally, H 2 O 2 is not a free radical but it is considered as a reactive oxygen species ROS because it can be transformed to other free radicals such as hydroxyl radical which mediate most of the toxic effects ascribed to H 2 O 2.

Myeloperoxidase can decompose H 2 O 2 into singlet oxygen and hypochlorous acid, a mechanism which phagocytes utilize to kill bacteria [ 15 ]. However, H 2 O 2 is a weak oxidizing agent that might directly damage enzymes and proteins which contain reactive thiol groups.

One of the most vital properties of H 2 O 2 over superoxide is its ability to freely traverse cell membranes [ 16 ]. Most ROS are usually converted to hydroxyl radical. Thus, it is usually the final mediator of most free radical induced tissue damage [ 17 ].

Hydroxyl radical is generated by various mechanisms but the most important is the in vivo mechanism due to decomposition of superoxide and hydrogen peroxide catalyzed by transition metals [ 18 ]. Transition metals generally contain one or more unpaired electrons and thus are capable to transfer a single electron.

Iron and copper are the most common transition metals capable of generating free radicals and much implicated in human diseases. As shown by Fenton [ 19 ], hydrogen peroxide can react with iron II or copper I to generate hydroxyl radical:.

L-arginine and L-citrulline are both converted to nitric oxide. Nitric oxide can further react with superoxide to form peroxynitrite. Protonated form of peroxynitrite ONOOH acts as a powerful oxidizing agent to sulfhydryl SH groups thereby causing oxidation of many molecules and proteins leading to cellular damage [ 20 ].

It can also cause DNA damage such as breaks, protein oxidation and nitration of aromatic amino acid residues in proteins. Reactive oxygen species and their oxidative stress induced damaged is summarized in Figure 1. Reactive oxygen species ROS -induced oxidative damage.

Source: Kohen and Nyska [ 21 ]. Continual influx and generation of ROS from endogenous and exogenous sources lead to oxidative damage of cellular components and may impair many cellular functions [ 22 ].

The most vulnerable biological targets to oxidative damage include proteins, enzymes, lipidic membranes and DNA [ 5 ]. Lipids: All cellular membranes are generally vulnerable to oxidative damage since they are highly rich in unsaturated fatty acid. The lipid damage due to ROS usually known as lipid peroxidation occurs in three stages [ 23 ].

The first stage, known as initiation involves the attack of a reactive oxygen metabolite capable of abstracting a hydrogen atom from a methylene group in the lipid due to the presence of a weak double bond. As such, the remaining fatty acid radical retains one electron and stabilizes by rearrangement of the molecular structure to form a conjugated diene.

These propagation reactions occur repeatedly leading to the peroxidation of several unsaturated lipid in the membrane. Hydrogen peroxide and superoxide radicals have weak effects on proteins except for proteins containing SH groups.

Following interaction with ROS, proteins can undergo direct damages such as damaging specific amino acid residues and changing their tertiary structures and indirect damages such as peroxidation, degradation and fragmentation. The consequences of protein damage include loss of enzymatic activity and altered cellular functions.

Protein oxidation products are usually keto, aldehydes and carbonyls compounds. Following protein oxidation, proteins are susceptible to many changes in their function which include inactivation, chemical fragmentation and increased proteolytic degradation [ 24 ].

Nucleic acid: Though DNA is a stable molecule, ROS can interact with it to cause several types of damages which include double- and single- DNA breaks, modification of DNA bases, loss of purines apurinic sites , DNA-protein cross-linkage, damage to the deoxyribose sugar and damage to the DNA repair system.

Hydroxyl radical is the most detrimental ROS that affects nucleic acids [ 25 ]. Also, hydroxyl radicals can attack pyrimidines leading to the formation of thymine peroxide, thymine glycols, 5- hydroxymethyl uracyl, and other such products.

When the concentration of ROS exceeds those of antioxidant neutralizing species, a condition known as oxidative stress occurs.

As reviewed from Rahman et al. Evidence via monitoring biomarkers such as the presence of ROS and RNS as well as antioxidant defense has indicated oxidative damage may be implicated in the pathogenesis of these diseases [ 29 ].

Oxidative stress also contributes to tissue injury following hyperoxia and irradiation. Evidence from studies have shown oxidative stress to play an important role in the pathogenesis and development of metabolic syndrome related disorders such as obesity, hypertension, diabetes, dyslipidemia etc.

as well as in cardiovascular related diseases such as myocardial infarction, aortic valve stenosis, angina pectoris, atherosclerosis and heart failure [ 32 , 33 , 34 , 35 ]. Cancer is another disease associated with ROS as ROS have been suggested to stimulate oncogenes such as Jun and Fos whose overexpression is directly associated with lung cancer [ 36 ].

In lung cancers, p53 can be mutated by ROS thereby losing its function of apoptosis and functioning as an oncogene [ 37 ]. Also, the development of gastric cancer has been thought to be due to increase production of ROS and RNS by Helicobacter pylori infection in human stomach [ 29 ].

Excess ROS in human kidney leads to urolithiasis [ 29 ]. ROS have also been reported to damage cellular components in cartilage leading to osteoarthritis [ 38 ] and has been shown to be involved in damaging the islets cells of the pancreas [ 39 ].

More so, hyperglycemia triggers ROS production in both tubular and mesangial cells of human kidney, making functional and structural changes in glomeruli causing diabetic nephropathy [ 40 ]. In response to the prevailing level of free radicals both from exogenous and endogenous sources, the human body developed a defense mechanism for protection against cellular damages.

These may involve direct and indirect mechanisms put in place by the body. Firstly, the indirect mechanisms are those mechanisms that do not directly act on the free radicals to eliminate them or convert them to less reactive forms. Rather this indirect system can act in several ways.

Certain regulatory mechanisms can control and regulate processes that lead to the endogenous production of ROS [ 41 ]. This may be transcriptional control of the enzymes that are involved in the generation of endogenous ROS. Another indirect approach consists of certain molecules and enzymes that are transported to oxidative-damage sites for repair of macromolecules.

This may include repair of damage DNA, protein or lipids. For examples damage oxidized adducts of DNA such as 8-hydroxydeoxyguanosine, thiamine glycol, and apurinic can be removed from a nucleotide sequence and replaced by a normal nucleotide base [ 42 ].

Also, certain molecules that can donate hydrogen atoms to damaged molecules are also considered as repair compounds. Molecules such as ascorbate or tocopherol can donate hydrogen atom to a fatty acid radical on cell membrane thereby repairing the membrane.

Certain natural cellular or surface barriers such as the skin or cell membranes act as indirect defense system against ROS by preventing exogenous ROS from entering the body or preventing certain endogenous ROS from reaching the target macromolecules.

Though these indirect defense mechanisms are helpful against ROS, they are usually non-specific and do not act directly on the ROS. This category of defense system which constitutes the antioxidant system is the most important because they directly act on free radicals either by decomposing, scavenging or converting free radicals to less reactive forms.

This defense mechanism constitute two groups; the enzymatic and non-enzymatic antioxidants. The enzymatic antioxidants include superoxide dismutase SOD , catalase, glutathione reductase GRx and glutathione peroxidase GPx. Superoxide dismutase SOD : SOD is an enzymatic antioxidant that exists in three forms in mammalian tissues and differs on their cofactor, subcellular location and tissue distribution.

Copper zinc superoxide dismutase CuZnSOD is present in the cytoplasm and organelles of almost all mammalian cells [ 43 ]. This enzyme has a molecular mass of about 32, kDa with two protein subunits, each containing a catalytically active copper and zinc atom.

Manganese superoxide dismutase MnSOD has a molecular mass of 40, kDa and is found in the mitochondria of almost all cells [ 44 ]. It consists of four protein subunits, each containing a single manganese atom. Extracellular superoxide dismutase ECSOD is a secretory copper and zinc containing SOD which is different from CuZnSOD [ 45 ].

It is synthesized only in fibroblasts and endothelial cells and expressed on the cell surface where it binds to heparan sulfates. Following its release from heparin, it is secreted into extracellular fluids and enters into the circulation.

Superoxide dismutase catalyzes the dismutation of superoxide to hydrogen peroxide:. Catalase: Catalase was the first antioxidant enzyme to be characterized. It is located mostly within the peroxisomes of cells which contain most of the enzymes capable of generating hydrogen peroxide.

It consists of four protein subunits, each containing a haem group and a molecule of NADPH [ 46 ]. Catalase is mostly present in liver and erythrocytes showing the greatest activities but is found in other tissues. Glutathione peroxidases GPx : Glutathione peroxidase is an enzyme which is synthesized mainly in the kidney and found in almost all tissues although it is highly found in the liver [ 47 ].

Its subcellular location is usually the cytosol and mitochondria. Selenium serves as its cofactor located at the active site of the enzyme and deficiency of selenium greatly affects the activity of the enzyme [ 48 ].

Glutathione peroxidases catalyze the oxidation of reduced glutathione GSH decomposing hydrogen peroxide or another species such as a lipid hydroperoxide:. The fact that GPx also acts on lipid hydroperoxides suggest it may be involved in repairing cellular damages due lipid peroxidation [ 49 ].

The activity of GPx is dependent on the constant availability of reduced glutathione which is regenerated from oxidized glutathione GSSG. Glutathione reductase GRx : GRx is a flavine nucleotide dependent enzyme and has a similar tissue distribution to glutathione peroxidase [ 49 ].

The role of GRx is to generate GSH from GSSG using NADPH in order to increase the ratio of reduced to oxidized glutathione:. The NADPH required by this enzyme to replenish the supply of reduced glutathione is provided by Glucosephosphate dehydrogenase GPD in the pentose phosphate pathway.

Competing pathway that utilizes NADPH such as the aldose reductase pathway may lead to a deficiency of reduced glutathione thereby limiting the action of glutathione peroxidase.

The non-enzymatic antioxidants are usually low-molecular-weight antioxidant LMWA compounds capable of preventing oxidative damage either by directly interacting with ROS or indirectly by chelating metals [ 50 ].

Transition metals are directly chelated by some of this LMWA thereby preventing them from participating in metal-mediated Haber-Weiss reaction [ 51 ].

Other direct acting LMWA molecules scavenge free radicals by donating electrons to free radicals to make them stable thereby preventing attacks of biological targets. These LMWA molecules also called scavengers may be advantageous over enzymatic antioxidants as they can penetrate cellular membranes and be localized in close proximity to the biological target due to their small size.

More so, these non-enzymatic antioxidants can interact together to scavenge free radicals and their scavenging activity may be synergic. Most scavengers originate from endogenous sources, such as biosynthetic processes and waste-product generation by the cell.

However, the number of LMWA synthesized by the living cell or generated as waste products such as histidine dipeptides, glutathione, uric acid, lipoic acid and bilirubin is limited [ 52 ].

More so, the concentration of scavenger must be sufficiently high to compete with the biological target on the deleterious species [ 50 ].

As such, exogenous sources of non-enzymatic antioxidants especially from plant diet and phytochemicals are needed to supplement the endogenous non-enzymatic antioxidants. The oxidative stress defense mechanism in humans is summarized in Figure 2. Oxidative stress defence mechanism.

Plants have long been consumed as food which is rich in vitamins and other nutrients that are useful for the body. Also, various plants were used in folk medicine for various therapeutic purposes. Though these uses, the notion of plant as a source of antioxidant became more evident in recent time as oxidative stress was considered a major attribute to most diseases in humans and the antioxidant defense system in human was usually not sufficient to overcome the free radical level in the body.

As such, plants have gained considerable interest as a source of antioxidants and so much research has been done to identify plants substances with antioxidant activities. Like other humans, plants do have enzymatic and non-enzymatic antioxidant defense systems to protect them against free radicals.

The enzymatic system includes catalase, SOD, glutathione peroxidase GPx , and glutathione reductase GRx [ 7 ], while non-enzymatic systems consist of low molecular weight antioxidants LMWA such as ascorbic acid, proline, glutathione, carotenoids, flavonoids, phenolic acids, etc.

and the high molecular weight antioxidants HMWA which are mostly secondary metabolites such as tannins [ 53 ]. The possible reason for the presence of these antioxidants in plants is that plants lack an immune system unlike animals thus, utilize the antioxidant defense system to protect them against microbial pathogens and animal herbivores.

Also, these phytochemicals serve as a defense system against environmental stress. Though plants have enzymatic antioxidants, it is usually difficult to isolate these enzymes for therapeutic uses in humans.

Also, they are usually denatured during food processing, preparation and not sufficiently present in diets such as fruits and vegetables.

On the contrary, non-enzymatic antioxidants are readily present in plants leaves, fruits and food in sufficient amounts and can easily be extracted from plants. For these reasons, this section will focus on the non-enzymatic plant antioxidants.

Glutathione: Glutathione is a low-molecular-weight, tripeptide of glutamic acid-cysteine-glycine containing a thiol. It exist as GSH in its reduced form and 2 GSH molecules can be joined via oxidation at their SH groups of the cysteine residue into a disulfide bridge to form GSSG which is the oxidized form.

GSH generally acts as a cofactor for glutathione peroxidase, thus serving as an indirect antioxidant by donating the necessary electrons for the decomposition of H 2 O 2.

Upon reacting with ROS, GSH becomes a glutathione radical, which can be reconverted to its reduced form [ 54 ]. Glutathione also has other cellular functions such metabolism of ascorbic acid [ 55 ].

Also, glutathione prevents the oxidation of SH protein groups and acts as a chelating agent for copper preventing its participation in the Haber-Weiss reaction [ 54 ]. The resultant tocopheroxyl radical in these reactions can be recycled to its active form but this radical is relatively stable in normal circumstances and insufficiently reactive to initiate lipid peroxidation itself, which makes it a good antioxidant [ 58 ].

Ascorbic acid Vitamin C : Ascorbic acid is a water-soluble antioxidant. It also functions as a chain breaker to terminate the lipid peroxidation chain reaction. Two molecules of ascorbate radicals can react rapidly to produce a molecule of ascorbate and a molecule of dehydroascorbate which do not have any scavenging activity.

Dehydroascorbate can be reconverted to ascorbate by the addition of two electrons catalyzed by oxidoreductase. More so, ascorbate can react with GSH to regenerate vitamin E in cell membranes [ 59 ]. Vitamin A: Though not fully understood, vitamin A is considered as a vital antioxidant that prevents humans LDL against copper stimulated oxidation [ 60 ].

The antioxidant potential of vitamin A was first revealed by Monaghan and Schmitt who showed that vitamin A can protect lipids against rancidity [ 61 ]. Bioflavonoids: This is a group of natural benzo-γ-pyran derivatives which are widely distributed in fruits and vegetables. They are the most abundant polyphenols found to possess strong antioxidant activities in scavenging free radicals.

They have generally been reported to protect against hydroxyl radical induced DNA damage [ 62 ]. Also, bioflavonoids are capable of chelating metal ions, such as copper or iron thereby preventing the generation of ROS [ 63 ]. These bioflavonoids include flavonol, flavones, flavonolols, flavanols, flavonone, anthocyanidin, isoflavone, etc.

Flavonoids: In plants, most flavonoids are attached to sugars glycosides , although they are occasionally found as aglycones. Most flavonoids are not completely absorbed and reach the circulatory system except for some flavanols and proanthocyanidins. However, at high concentrations of cupric ion, quercetin is reported to be a carcinogenic agent by enhancing DNA damage via ROS [ 64 ].

Therefore, it is very important to consider the concentration of the chelating metal ions such as copper or iron while evaluating the protective or degenerative effects of quercetin and other bioflavonoids.

Anthocyanidin is a class of flavonoids with antioxidant potentials. They are effective in the inhibition of lipid oxidation due to their metal ion-chelating activity. In general, flavonoids are oxidized by radicals, resulting in a more stable, less-reactive radical.

In this reaction, flavonoids stabilize the ROS by reacting with them to become a flavonoids radical. This is achieved due to high reactive hydroxyl group of the flavonoids as shown below.

As reviewed from Nijveldt et al. Other flavonoids may act as antioxidants by inhibiting the activity of free radical generating enzymes such as xanthine oxidase and nitric-oxide synthase.

By scavenging radicals, flavonoids can inhibit LDL oxidation in vitro. This action protects the LDL particles and, theoretically, flavonoids may have preventive action against atherosclerosis.

Extensive damage can lead to death of the cell; this may be by necrosis or apoptosis depending on the type of cellular damage. When a cell membrane or an organelle membrane is damaged by free radicals, it loses its protective properties. This puts the health of the entire cell at risk. Cells normally defend themselves against ROS damage through the use of enzymes such as superoxide dismutase and catalase.

Small molecule antioxidants such as ascorbic acid vitamin C , uric acid, and glutathione also play important roles as cellular antioxidants. Similarly, polyphenol antioxidants assist in preventing ROS damage by scavenging free radicals.

The negative effects of ROS on cell metabolism include roles in programmed cell death and apoptosis, whereas positive effects include induction of host defense genes and mobilization of ion transport systems.

In particular, platelets involved in wound repair and blood homeostasis release ROS to recruit additional platelets to sites of injury. These also provide a link to the adaptive immune system via the recruitment of leukocytes.

Reactive oxygen species are involved in cardiovascular disease, hearing impairment via cochlear damage induced by elevated sound levels, ototoxicity of drugs such as cisplatin, and in congenital deafness in both animals and humans. Reactive oxygen species ROS are very small molecules and are highly reactive due to the presence of unpaired valence shell electrons.

ROS is formed as a natural byproduct of the normal metabolism of oxygen and have important roles in cell signaling. However, during times of environmental stress ROS levels can increase dramatically, which can result in significant damage to cell structures.

Platelets involved in wound repair and blood homeostasis release ROS to recruit additional platelets to sites of injury.

Generally, harmful effects of reactive oxygen species on the cell are most often like -Damage of DNA, oxidations of polydesaturated fatty acids in lipids, oxidations of amino acids in proteins, oxidatively inactivates specific enzymes by oxidation of co-factors Table 1.

Transferin iron Vitamin C, Ferritin iron beta-carotene, Myoglobin iron. Thiols GSH, Lipoic acid, N-acetyl cysteine NADH and NADPH Ubiquinone. Table 1 Reactive oxygen species and their corresponding neutralising antioxidants and also additional antioxidants These are the list of antioxidants that help to include in the diet and manage to scavenge the free radical that can develop the steps of neurodegeneration.

All aerobic forms of life maintain elaborate anti-free-radical defense systems, also known as antioxidant systems. Enzymes: The defense enzyme, superoxide dismutase SOD , takes hold of molecules of superoxide—a particularly destructive free radical-and changes them to a much less reactive form.

SOD and another important antioxidant enzyme set, the glutathione system, work within the cell. Self repair: The body also has systems to repair or replace damaged building blocks of cells. Most protein constituents in the cell are completely replaced every few days.

Scavenger enzymes break used and damaged proteins into their component parts for reuse by the cell. Nutrients: Vitamins and other nutrients neutralize the oxy radicals' and serves as second line of defense. Among the many substances used are Vitamins C and E, beta-carotene, and bioflavonoids.

Free radical or oxidative injury may be a fundamental mechanism underlying a number of human neurologic diseases. OS can cause cellular damage and subsequent cell death because the reactive oxygen species ROS oxidize vital cellular components such as lipids, proteins, and DNA.

Therapy using free radical scavengers antioxidants has the potential to prevent, delay, or ameliorate many neurologic disorders. However, the biochemistry of oxidative pathobiology is complex, and optimum antioxidant therapeutic options may vary and need to be tailored to individual diseases. In vitro and animal model studies support the potential beneficial role of various antioxidant compounds in neurologic disease.

However, the results of clinical trials using various antioxidants, including vitamin E, tirilazad, N-acetylcysteine, and ebselen, have been mixed. Moreover, therapy with antioxidants may need to be given early in chronic insidious neurologic disorders to achieve an appreciable clinical benefit.

Pre-disease screening and intervention in at-risk individuals may also need to be considered in the near future. Oxidative stress is a general term used to describe a serious imbalance between the production of reactive oxygen species ROS and reactive nitrogen species RNS on the one hand, and the levels of antioxidant defences on the other.

Any prolonged imbalance results in oxidative damage to cells, tissues, and organs. External sources of ROS include radiation, UV light, chemical reagents, pollution, cigarette smoke, drugs of abuse, and alcohol.

At low or moderate levels, ROS and RNS exert beneficial effects on cellular responses and immune function. However, at high concentrations, they cause oxidative stress, and subsequent damage to proteins, lipids, and DNA. Why the need of the free radical in neurodegeneration: The harmful effects of ROS cause damage to macromolecules such as proteins, lipids, polysaccharides or nucleic acids, are termed oxidative stress.

The intrinsic properties of neurons make them highly vulnerable to the detrimental effects of ROS: high metabolic rates; a rich composition of fatty acids prone to peroxidation; high intracellular concentrations of transition metals, capable of catalyzing the formation of reactive hydroxyl radicals; low levels of antioxidants; and reduced capability to regenerate.

Neurons have intense energy demands which are met by mitochondria. Mitochondria are both targets and important sources of ROS. It has been shown that oxidative stress stimulates mitochondrial fission; the addition of hydrogen peroxide to cultured cerebellar granule neurons induced mitochondrial fragmentation within one hour of treatment.

It was also shown that nitric oxide causes increased mitochondrial fission in neurons, prior to the onset of neuronal loss in a mouse model of stroke.

On the other hand, expression of Mfn or a dominant negative Drp1 in cultured neurons, was protective against oxidative insults. The generation of ROS appears to be increased in damaged mitochondria, and in cells with compromised mitochondrial function.

Oxidative stress within mitochondria can lead to a vicious cycle in which ROS production progressively increases leading, in turn, to progressive augmentation of damage.

Nucleic acid oxidation occurs in neurons during disease and is detected as elevated levels of 8-hydroxydeoxyguanosine 8-OHDG in DNA and 8-hydroxyguanosine in RNA.

Hydroxyl radical-mediated DNA damage often results in strand breaks, DNA-protein crosslinking, and base-modifications.

All of these events can lead to neuronal injury. It is known that generation of ROS results in an attack not only on DNA, but also on other cellular components involving polyunsaturated fatty acid residues of phospholipids, which are extremely sensitive to oxidation. Once formed, peroxyl radicals ROO· can be rearranged via a cyclisation reaction to endoperoxides precursors of malondialdehyde with the final product of the peroxidation process being malondialdehyde MDA.

The major aldehyde product of lipid peroxidation other than malondialdehyde is 4-hydroxynonenal HNE. Increased production of ROS also results in protein oxidation.

Oxidation of cysteine residues may lead to the reversible formation of mixed disulfides between protein thiol groups —SH and low molecular weight thiols, in particular glutathione GSH, S-glutathiolation.

The concentration of carbonyl groups, generated by many different mechanisms is a good measure of ROS-mediated protein oxidation. The generation of isoprostanes has been shown to be a sensitive measure of lipid peroxidation, which are increased in cerebrospinal fluid CSF of HD patients.

ROS are often present in brain regions affected by neurodegenerative diseases. Studies in both HD patients and experimental models of HD support a role for oxidative stress and ensuing mitochondrial dysfunction in mediating the neuronal degeneration observed in HD.

Oxidative damage in HD has been previously reviewed in detail. The accumulation of ROS in neurons, and subsequent oxidative stress are attenuated by free radical scavengers, which can be categorized as enzymatic or non-enzymatic antioxidants.

Enzymatic antioxidants constitute one of the defense mechanisms against free radicals. These include superoxide dismutase SOD , glutathione peroxidase Gpx and catalase CAT. Non-enzymatic antioxidants are represented by ascorbic acid Vitamin C , α-tocopherol Vitamin E , glutathione GSH , retinoic acid, carotenoids, flavonoids, and other antioxidants.

The therapeutic approaches tested in vitro or in toxin or transgenic models of HD are given below-. As we know that neurodegenerative disorders is an important source of morbidity and mortality in human mankind. Free radical involvement offers a novel therapeutic target in the management of Huntington diseases.

However, it will happen only if the mechanism of action of the free radical can be understood properly. The antioxidant therapy can be used over the free radical generation and target the free radical that are responsible for the neurodegeneration such as HD.

Free-radical-mediated oxidative injury plays a major role in the defection of various diseases and trauma; chronic neurogenic and other neurodegeneration disease can be recognized. We know that oxygen is an essential molecule for survival of majority of living organisms in the world as well as the inside the body.

Oxidative stress mostly a harmful condition that occurs when there is an excess of free radicals will be generated or a decrease in antioxidant levels in the body.

So, this review suggests the use of antioxidants to manage the disease state. Antioxidants quench oxidative stress by 1working to off-pair free radical generation and stopping them from starting the chain reactions that contribute to develop Huntington disease.

Oxidative stress OS has been responsible in the pathophysiology of various life threatening starts disease such as neurological and neurodegenerative diseases.

Oxygen Species generally a free radical species can cause cellular damage and subsequent cell death because the reactive oxygen species which oxidize sensitive cellular components that makes a major part of proteins, lipids, ribose sugar and genetic material.

However, the excitatory amino acid glutamate is the major amino acid that can prevent such kind of neurodegeneration that are responsible for Huntington disease populations that are at high risk, such as elderly and newly diagnosed patients. In this review we have to find the new way and the use of certain antioxidants to remove the wastes of free radical generation and scavenging properties of the antioxidants to manage in the disease and cure them.

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Home JAPLR Role of free radicals and certain antioxidants in the management of huntingtons disease a review. Journal of. Review Article Volume 7 Issue 4. Types of long lived radicals Stable radicals : The prime example of a stable radical is molecular oxygen O 2.

Formation of free radicals Normally, bonds do not split to leave a molecule with an odd and an unpaired electron. Chain reactions involving free radicals can usually be divided into three distinct processes: Initiation, Propagation, Termination. Lipids Peroxidation of lipids in cell membranes can damage cell membranes by disrupting fluidity and permeability.

Proteins Direct damage to proteins can be caused by free radicals. DNA Fragmentation of DNA caused by free radical attack causes activation of the poly ADP-ribose synthetase enzyme.

Oxidative stress Oxidative stress is a general term used to describe a serious imbalance between the production of reactive oxygen species ROS and reactive nitrogen species RNS on the one hand, and the levels of antioxidant defences on the other. The therapeutic approaches tested in vitro or in toxin or transgenic models of HD are given below- In vitro studies Metalloporphyrins, metal-containing catalytic antioxidants, have emerged as a novel class of potential therapeutic agents that scavenge a wide range of reactive oxygen species.

A manganese porphyrin has been reported to significantly reduce cell death in an in vitro chemical model of HD. Treating cultured rodent cortical neurons with glutamate resulted in significant neurodegeneration, which was completely rescued with ascorbic acid co-treatment.

Using a neuronal cell-based assay, glutamate-induced neuronal death was significantly attenuated in a dose-dependent manner by α-tocopherol. Also, treatment with idebenone in this in vitro model resulted in complete neuroprotection in a dose-dependent manner. Melatonin significantly reduced DNA damage and improved neuronal survival.

In another study using the 3-NP model of HD, melatonin treatment significantly ameliorated the increase in lipid peroxidation, protein carbonyls and SOD activity within the striatum. Selenium dose-dependently reduced lipid peroxidation and significantly improved neuronal morphology within the striatum of rats treated with quinolinic acid, an N-methyl-D-aspartate antagonist that results in striatal neurodegeneration.

Creatine also buffers intracellular energy reserves through its intermediate, phosphocreatine PCr ; stabilizes intracellular calcium; and inhibits activation of the mitochondrial transition pore.

Creatine supplementation significantly reduces striatal lesion volumes produced by the neurotoxins 3-NP and malonate. The antioxidant compound CoQ10 also demonstrated efficacy in murine models of HD.

CoQ10, ubiquinone, is a lipid-soluble benzoquinone which, when reduced to ubiquinol, which possesses significant antioxidant potential.

Open access raficals chapter. Submitted: 18 January Reviewed: 22 March Role of free radicals 07 November com customercare Role of free radicals. Free Role of genetics in heart health or reactive frde species ROS generated from various sources frde the environment as well as from cellular processes in the body are of serious health challenges. Overwhelming levels of these free radicals disrupt the antioxidant defense system in the body thereby damaging cell membranes and cellular macromolecules such as proteins, lipids and nucleic acids leading to cell death or causing mutations leading to uncontrolled cell division.

Oxidative stress plays fee essential role in the pathogenesis fdee chronic diseases such as cardiovascular diseases, diabetes, neurodegenerative diseases, rdaicals cancer. Long term exposure to RRole levels of pro-oxidant factors radicls cause structural defects at a og DNA level, as well ffee functional radivals of several enzymes and cellular structures oc to aberrations Benefits of thermogenesis supplements gene expression.

Pf modern lifestyle associated Healthy diabetic eating processed frfe, exposure to a wide range of chemicals and Hyperglycemia in children of exercise plays an frew role in oxidative stress induction.

However, the use of medicinal plants with antioxidant feee has been exploited for their ability fgee treat Rlle prevent several human pathologies in which oxidative stress seems to be one of radcials causes.

In this review we radkcals the Role of free radicals in which oxidative stress is one of the triggers and rsdicals plant-derived antioxidant compounds with their mechanisms of antioxidant frre that can ardicals in the prevention of these diseases.

Finally, both Nutrition for ultra distance events beneficial and detrimental Alternative treatments for insulin resistance of antioxidant molecules that are Probiotic Foods for Skin Conditions to reduce radicalss stress in several human conditions are discussed.

Radocals natural biological processes in raricals bodies, such as breathing, digesting food, metabolize alcohol and drugs, Probiotics for wound healing turning fats into energy produce harmful compounds called free radicals.

If this system tree not cope properly, free radicals can trigger a negative chain reaction in the frew, a reaction that Low GI food swaps destroy the cell membrane, oc the action of major Rile, prevent cellular processes necessary for proper functioning Rkle the Hydration and flexibility training, prevent normal cell Role of free radicals, Effective body detox deoxyribonucleic acid Role of free radicalsand block energy generation Kurutas, Role of free radicals, Oxidative stress is reported ot associate Role of free radicals the development of several metabolic, chronic disorders or Weight management for beginners Finkel and Rol, ; Radicalw et al.

The theory of free radicals of Natural metabolism boosters has been known for over 50 years, cree, it is only in free last two decades that their rxdicals in the development radicqls diseases were rdaicals and, thus, the beneficial effects of antioxidants Raidcals been widely raicals Liu, Radivals radicals Roel an essential role in several Rol processes.

Rple of these are necessary for life, such as the raadicals destruction of bacteria by phagocytes, especially by Mental resilience training and macrophages. Researchers Rope that free radicals are also fee in radjcals cellular signaling processes, known rfee redox signaling Finkel and Holbrook, At low-to-moderate amounts, ROS are beneficial both in regulating processes involving the maintenance fre homeostasis frwe well as a wide variety of cellular functions Finkel and Holbrook, ; Rree et al.

Excessive ROS production determines fref modification of cellular proteins and the alteration of their functions, leading to cellular dysfunction and rradicals of vital cellular processes Finkel and Holbrook, Rolw Kaminski et al.

High ROS levels cause lipid, protein, and DNA damage. In particular, ROS Organic sustainable fashion break the lipid membrane eadicals increase membrane fluidity Ro,e permeability.

Protein damage raducals site-specific amino acid modification, peptide chain racicals, cross-linked reaction products aggregation, electric charge Rolle, enzymatic inactivation, and proteolysis susceptibility Ayala et al.

Finally, Freee can damage DNA through oxidizing deoxyribose, breaking strand, oRle nucleotides, modifying bases and crosslinking DNA-protein Sharma et al. Dree oxygen free radicals are superoxide and rzdicals radical. They are derived from Rloe oxygen under chemical reduction conditions.

Excessive amounts of Role of free radicals free radicals can lead to cell radocals and apoptosis, rfee to many diseases such as cancer, stroke Tsatsakis A. et Subcutaneous fat storage. Many RRole are thought to be the Roke of interactions between kf radicals and DNA that lead to mutations that affect the cell frde and which then leads to neoplasia Reuter et al.

Because free Herbal energy-boosting remedies are necessary for life, the body has several enzymatic mechanisms Rolw Role of free radicals radically induced damage and to protect against excessive raadicals of free radicals.

Raducals play a vital role in these defense mechanisms. In healthy ot, protection against the radiclas effects Role of free radicals reactive oxygen species is achieved ffree maintaining frfe delicate balance radicaps oxidants and raadicals.

The continuous production of free radicals in aerobic organisms ardicals therefore be equalized by a Role of free radicals rate Rolr antioxidant consumption. Enzymatic or non-enzymatic, antioxidants are Role of free radicals that prevent fref formation of free radicals, and seek and neutralize or repair ffree damage caused by them Clark et al.

The protection against ardicals damage and chronic diseases radcials achieved through a variety of endogenous and exogenous antioxidants Cadet et al. Rooe homeostasis od ensured by various antioxidant systems present both in plants Fred et al.

Natural ROS production through the mitochondrial Role of free radicals chain is radiclas since ROS can be metabolically RRole, but, at the Fat burning exercises time, harmful to cells in some raducals Hsu radicasl al.

Conversely, in pathological ravicals stress conditions, Rooe overwhelms antioxidant systems leading to an imbalance, which, in turn, causes oxidative stress and irreversible changes in cell compounds, including proteins, carbohydrates and lipids, in addition to being able to disrupt normal cellular-signaling mechanisms Birben et al.

In autoimmune diseases, free radicals can change the expression of self-antigen-type proteins, increasing their immune response or changing their antigenic profile.

The immune response can also be influenced by external antioxidants such as allergens in susceptible individuals. Pollen from some plant species has been shown to contain nicotinamide adenine dinucleotide phosphate oxidase NADPH oxidasewhich induces an inflammatory response in the airways with specific symptoms due to infiltration with proinflammatory cytokines, TNF-alpha and interleukins from epithelial cells.

In cancers, alteration of purine or pyrimidine in the structure of cellular DNA, which is associated with a number of other reactions that produce oxides and free radicals, may be the cause of neoplasms.

If the intracellular mechanisms of repair of oxidative defects are insufficient or disturbed in turn by the oxidative factors present, there are definitive consequences in some genes or products resulting from the expression of these genes, which causes mutagenesis and modification of the apoptotic mechanism of the cell, thus resulting in the tumor cell Buj and Aird, In the long term, the changes spread and self-sustain with the permanent activation of the autoimmune response and the accumulation of local proinflammatory factors, for example: TNF-alpha, proteases, kinases.

These factors favor tissue necrosis and accelerate tissue growth with the appearance of new modified cells that maintain the immune response and propagate the initial genetic defects with chaotic and extensive multiplication; also, oxidative stress produces structural changes of cell membranes with decreased adhesion, and the migration of altered tumor cells in neighboring tissues or in distant blood and lymph Forni et al.

In cellular aging, two theories on the mechanisms of cellular aging are currently accepted: the mitochondrial theory and the free radical theory.

They support the hypothesis that mitochondria are affected by an increased level of intracellular free radicals, which leads to the alteration of their function and a decreased cellular regenerative capacity.

At the same time, the progressive accumulation of intracellular oxidizing factors that exceed the antioxidant capacity is also accepted. Under these conditions, the biological decline of the respective tissue and the reduction of the adaptive c pacity to stress appear.

Subsequently, regardless of the mechanism involved, in mitochondrial DNA damage or in the direct involvement of prooxidant factors in cellular mechanisms, the cellular response to stress will produce an overexpression of proinflammatory genes with increasing levels of prooxidant factors Liguori et al.

Oxidative stress stimulates the immune response and causes allergic diseases, such as asthma, allergic rhinitis, atopic dermatitis, or food allergies.

This means that the antioxidant protection system of patients with allergic diseases is outdated compared to that of healthy individuals Sackesen et al. Supplementation with antioxidants could therefore compensate for the increased inflammatory and oxidative stress processes in asthma patients.

However, Murr et al. The modern lifestyle associated with an unhealthy diet, lack of physical exercise, exposure to a combination of chemicals from different sources pesticides Tsatsakis A.

It can contribute to the increasing burden of chronic diseases, as is suggested by several experimental and human studies Fenga et al.

This comprehensive review aims to provide strong evidence that antioxidants may contribute to the amelioration of some chronic-degenerative conditions, in addition to being able to promote healthy aging. Free radicals are generally produced as a result of the influence of external factors, such as pollution, cigarette smoke, or internally, as a result of intracellular metabolism if the antioxidant mechanisms are overwhelmed Figure 1.

Figure 1. Schematic presentation of the sources of free radicals and their effects on the human body. Environmental triggers, such as exposure to cigarette smoke, UV radiation, heavy metal ions, ozone, allergens, drugs or toxins, pollutants, pesticides, or insecticides, may all contribute to the increase of ROS production in cells Antunes dos Santos et al.

Ionizing radiation acts by converting hydroxyl radicals, superoxides and organic radicals into organic hydroperoxides and hydrogen peroxide. Subsequently, the peroxides react with the metal ions of Fe and Cu at the cellular level through redox reactions with secondary oxidative activity.

Several studies have shown that the exposure of fibroblasts to alpha particles has led to an intracellular increase of oxygen and an accelerated production of peroxide at this level Spitz et al.

Ultraviolet radiation UVA triggers oxidative reactions by stimulating riboflavin, porphyrins and NADPH-oxidase, with the production of 8-oxo-guanine as the main result and the decrease of intracellular glutathione GSH level with a return to normal after cessation of exposure Marchitti et al.

Heavy metals play an essential role in the production of free radicals Ściskalska et al. Iron, copper, cadmium, nickel, arsenic, and lead can induce free radicals by Fenton or Haber-Weiss type reactions, but also by direct reactions between metal ions and cellular compounds with similar effects — for example, the production of thiol type radicals.

Lead triggers lipid peroxidation and increases glutathione peroxidase concentration in brain tissue. Arsenic induces the production of peroxides, superoxides, nitric oxide and inhibits antioxidant enzymes such as glutathione-transferase, glutathione-peroxidase, and glutathione-reductase by binding to the sulfhydryl group.

The free radicals generated from these reactions can affect DNA, with substitutions of some DNA bases such as guanine with cytosine, guanine with thymine and cytosine with thymine Jan et al. Exposure to ozone can affect lung function even in healthy individuals by increasing inflammatory infiltrate in the respiratory epithelium Wu X.

The main endogenous sites of cellular redox-reactive species generation-including ROS and reactive nitrogen species RNS comprise mitochondrial electron transport chain ETCendoplasmic reticulum ERperoxisomes, membrane-bound NADPH oxidase NOX isoforms 1—5, dual oxidases Duox 1 and 2 complexes, and nitric oxide synthases isoforms 1—5 NOS1—3.

The complexes I and III of mitochondrial ETC produces superoxide anion Rodriguez and Redman, The mitochondrial ETC is considered to be the primary endogenous source of ROS but other internal sources are also present. Other sources of ROS, primarily H 2 O 2are microsomes and peroxisomes. Immune cells, such as macrophages and neutrophils, can also generate ROS due to their oxygen-dependent mechanisms to fight against invading microorganisms based on NOX2 isoform Curi et al.

Furthermore, dysregulated ROS signaling may contribute to a multitude of diseases associated with oxidative stress Finkel, ROS are produced in mitochondria during aerobic metabolism Rodriguez and Redman, ROS generation within mitochondria oxidative metabolism is closely associated with ATP synthesis oxidative phosphorylation.

In aerobic organisms, the coupling of these reactions is the primary source of energy Papa et al. Mitochondria serve as a major ROS generator and, at the same time, as a ROS receptor. Covalent and enzymatic changes in proteins during or after protein biosynthesis as well as during protein cleavage or degradation promote disease through oxidative damage and mitochondrial dysfunction.

These post-translational changes participate in the regulation of mitochondrial function through free radical species and other messengers Hu and Ren, Since oxidative phosphorylation is a leaky process, 0. This produces an incompletely O 2 reduction Hamanaka et al.

Because of the anionic properties of superoxide radicals, they diffuse through biological lipid membranes at the meager extent. They are sequentially reduced inside cells to form hydrogen peroxide and hydroxyl radical Bartosz, Furthermore, peroxyl and alkoxyl radicals, as well as hypochlorite ions, are also formed Valko et al.

All these types of ROS can be very harmful to cells; in fact, they can oxidize and subsequently inactivate several functions of cell components and even DNA Valko et al.

All these processes may trigger irreversible apoptotic and necrotic cell death. Several studies indicate that human cells can also actively trigger ROS production at small doses, as part of signaling pathways, regulating cell survival and proliferation, as a defense mechanism against invaders Bartosz, ; Sena and Chandel, In particular, specific enzymatic systems, such as the NOX family, dedicated explicitly to superoxide radical production with physiological signaling purposes, are developed by cells Bedard and Krause, Beyond this, other internally generated sources of ROS are present in humans, including:.

i oxidative burst from phagocytes white blood cells during bacteria and virus killing and foreign proteins denaturation.

iv detoxification of toxic substances i. ROS decrease phosphatase activity, by inhibiting catalytic regions susceptible to oxidation, and, thus, enhance protein tyrosine phosphatase PTP phosphorylation and influences signal transduction Bedard and Krause, ROS can also improve signal transduction pathways that disturb the nuclear factor-κB NF-κB activation and translocation of this into the nucleus.

The DNA binding potential of oxidized NF-κB is significantly reduced. However, NF-κB may be decreased by TR or redox factor 1 Kabe et al. The above provokes ROS and RNS so it can strongly affect NF-κB-dependent inflammatory signals.

Cyclopentenones are electrophilic anti-inflammatory prostaglandins which are conjugated with the reactive thiols of ROS-modified peptides and proteins and thus dampens ROS-mediated NF-κB signaling Homem de Bittencourt and Curi, On the other hand, endogenous stress has an intracellular origin. Several studies have highlighted the role of cultural cell conditions, altering gene expression patterns of different genes and their DNA stability.

Metabolic processes trigger different types of ROS, that are able to, if present at inadequate levels, oxidize DNA and induce various damage, such as double-stranded DNA breaks and deficiencies, often found in human tumors De Bont and van Larebeke,

: Role of free radicals

Analytical & Pharmaceutical Research

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Everything You Should Know About Oxidative Stress. Medically reviewed by Timothy J. Legg, PhD, PsyD — By Megan Dix, RN, BSN — Updated on September 29, Effects Risk factors Prevention Takeaway Oxidative stress is an imbalance between free radicals and antioxidants in your body.

Effects of oxidative stress on the body. What are the risk factors? Managing and preventing oxidative stress. The takeaway. How we reviewed this article: Sources. Healthline has strict sourcing guidelines and relies on peer-reviewed studies, academic research institutions, and medical associations.

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Oxidative Stress: Your FAQs Answered. Your 5-Minute Read on Fighting Brain Fog. What Is Carbon 60 C60? Your FAQs Answered. All of these events can lead to neuronal injury. It is known that generation of ROS results in an attack not only on DNA, but also on other cellular components involving polyunsaturated fatty acid residues of phospholipids, which are extremely sensitive to oxidation.

Once formed, peroxyl radicals ROO· can be rearranged via a cyclisation reaction to endoperoxides precursors of malondialdehyde with the final product of the peroxidation process being malondialdehyde MDA.

The major aldehyde product of lipid peroxidation other than malondialdehyde is 4-hydroxynonenal HNE. Increased production of ROS also results in protein oxidation. Oxidation of cysteine residues may lead to the reversible formation of mixed disulfides between protein thiol groups —SH and low molecular weight thiols, in particular glutathione GSH, S-glutathiolation.

The concentration of carbonyl groups, generated by many different mechanisms is a good measure of ROS-mediated protein oxidation. The generation of isoprostanes has been shown to be a sensitive measure of lipid peroxidation, which are increased in cerebrospinal fluid CSF of HD patients.

ROS are often present in brain regions affected by neurodegenerative diseases. Studies in both HD patients and experimental models of HD support a role for oxidative stress and ensuing mitochondrial dysfunction in mediating the neuronal degeneration observed in HD.

Oxidative damage in HD has been previously reviewed in detail. The accumulation of ROS in neurons, and subsequent oxidative stress are attenuated by free radical scavengers, which can be categorized as enzymatic or non-enzymatic antioxidants.

Enzymatic antioxidants constitute one of the defense mechanisms against free radicals. These include superoxide dismutase SOD , glutathione peroxidase Gpx and catalase CAT.

Non-enzymatic antioxidants are represented by ascorbic acid Vitamin C , α-tocopherol Vitamin E , glutathione GSH , retinoic acid, carotenoids, flavonoids, and other antioxidants. The therapeutic approaches tested in vitro or in toxin or transgenic models of HD are given below-.

As we know that neurodegenerative disorders is an important source of morbidity and mortality in human mankind. Free radical involvement offers a novel therapeutic target in the management of Huntington diseases. However, it will happen only if the mechanism of action of the free radical can be understood properly.

The antioxidant therapy can be used over the free radical generation and target the free radical that are responsible for the neurodegeneration such as HD. Free-radical-mediated oxidative injury plays a major role in the defection of various diseases and trauma; chronic neurogenic and other neurodegeneration disease can be recognized.

We know that oxygen is an essential molecule for survival of majority of living organisms in the world as well as the inside the body.

Oxidative stress mostly a harmful condition that occurs when there is an excess of free radicals will be generated or a decrease in antioxidant levels in the body. So, this review suggests the use of antioxidants to manage the disease state.

Antioxidants quench oxidative stress by 1working to off-pair free radical generation and stopping them from starting the chain reactions that contribute to develop Huntington disease. Oxidative stress OS has been responsible in the pathophysiology of various life threatening starts disease such as neurological and neurodegenerative diseases.

Oxygen Species generally a free radical species can cause cellular damage and subsequent cell death because the reactive oxygen species which oxidize sensitive cellular components that makes a major part of proteins, lipids, ribose sugar and genetic material.

However, the excitatory amino acid glutamate is the major amino acid that can prevent such kind of neurodegeneration that are responsible for Huntington disease populations that are at high risk, such as elderly and newly diagnosed patients.

In this review we have to find the new way and the use of certain antioxidants to remove the wastes of free radical generation and scavenging properties of the antioxidants to manage in the disease and cure them. This is an open access article distributed under the terms of the, which permits unrestricted use, distribution, and build upon your work non-commercially.

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Home JAPLR Role of free radicals and certain antioxidants in the management of huntingtons disease a review. Journal of. Review Article Volume 7 Issue 4. Types of long lived radicals Stable radicals : The prime example of a stable radical is molecular oxygen O 2.

Formation of free radicals Normally, bonds do not split to leave a molecule with an odd and an unpaired electron.

Chain reactions involving free radicals can usually be divided into three distinct processes: Initiation, Propagation, Termination. Lipids Peroxidation of lipids in cell membranes can damage cell membranes by disrupting fluidity and permeability.

Proteins Direct damage to proteins can be caused by free radicals. DNA Fragmentation of DNA caused by free radical attack causes activation of the poly ADP-ribose synthetase enzyme. Oxidative stress Oxidative stress is a general term used to describe a serious imbalance between the production of reactive oxygen species ROS and reactive nitrogen species RNS on the one hand, and the levels of antioxidant defences on the other.

The therapeutic approaches tested in vitro or in toxin or transgenic models of HD are given below- In vitro studies Metalloporphyrins, metal-containing catalytic antioxidants, have emerged as a novel class of potential therapeutic agents that scavenge a wide range of reactive oxygen species.

A manganese porphyrin has been reported to significantly reduce cell death in an in vitro chemical model of HD. Treating cultured rodent cortical neurons with glutamate resulted in significant neurodegeneration, which was completely rescued with ascorbic acid co-treatment.

Using a neuronal cell-based assay, glutamate-induced neuronal death was significantly attenuated in a dose-dependent manner by α-tocopherol. Also, treatment with idebenone in this in vitro model resulted in complete neuroprotection in a dose-dependent manner.

Melatonin significantly reduced DNA damage and improved neuronal survival. In another study using the 3-NP model of HD, melatonin treatment significantly ameliorated the increase in lipid peroxidation, protein carbonyls and SOD activity within the striatum.

Selenium dose-dependently reduced lipid peroxidation and significantly improved neuronal morphology within the striatum of rats treated with quinolinic acid, an N-methyl-D-aspartate antagonist that results in striatal neurodegeneration.

Creatine also buffers intracellular energy reserves through its intermediate, phosphocreatine PCr ; stabilizes intracellular calcium; and inhibits activation of the mitochondrial transition pore.

Creatine supplementation significantly reduces striatal lesion volumes produced by the neurotoxins 3-NP and malonate. The antioxidant compound CoQ10 also demonstrated efficacy in murine models of HD. CoQ10, ubiquinone, is a lipid-soluble benzoquinone which, when reduced to ubiquinol, which possesses significant antioxidant potential.

In addition, CoQ10 can induce increases in vitamin E, enhancing its antioxidant capacity. Using the mitochondrial toxins malonate. FK also known as Tacrolimus or Fujimycin is an immunosuppressive drug mainly used to lower allograft rejection and also in topical preparations.

Recently, the neuroprotective effects of FK were reported in 3-NP model of HD. FK treatment significantly reduced behavioral deficits, MDA levels, nitrite concentration, and restored antioxidant enzyme levels of SOD and catalase, and levels of dopamine and norepinephrine in the striatum, cortex, and hippocampus.

Lycopene, a carotenoid pigment and phytochemical naturally found in fruits and vegetables, reduced oxidative stress markers and improved behavior in a 3-NP induced rodent model of HD.

In transgenic mouse models of HD Lipoic acid is an essential cofactor for many enzyme complexes and is present in mitochondria as the cofactor for pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase.

It is an effective antioxidant and has been used to treat disease associated with impaired energy metabolism. Pyruvate plays a major role in glycolysis, and also possesses significant antioxidant capacity. Creatine exists in the cell both as free creatine and phosphocreatine PCr which together comprise the total creatine pool.

In tissues with high energy requirements such as skeletal muscle and brain, PCr serves as a short term energy buffer in which adenosine diphosphate is phosphorylated to adenosine triphosphate.

This phosphorogroup transfer is catalyzed by the important creatine kinase CK enzyme. It is effective in preventing cell membrane damage caused by reactive oxygen species.

Recently, administration of a relatively high dose of L-carnitine to NQ transgenic mice was shown to extend the survival, ameliorate motor performance, and decrease the number of intranuclear aggregates. Synthetic triterpenoids, which are analogues of 2-Cyano-3, Dioxooleana-1,9-DienOic acid CDDO , are of great interest because of their antioxidant and anti-inflammatory properties.

Triterpenoids significantly preserved the striatal volumes of the NQ mice, by preventing the atrophy of the medium spiny neurons, and they rescued behavioral deficits, extended survival, attenuated peripheral pathology, and reduced 8-OHdG, MDA and 3-nitrotyrosine immune-reactivity in the striatum.

The Huntington's Disease Collaborative Research Group. A novel gene containing a rinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes.

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Ann NY Acad Sci. Cowan CM, Raymond LA. Selective neuronal degeneration in Huntington's disease. Curr Top Dev Biol. Walker FO. Huntington's Disease.

Semin Neurol. Berardelli A, Noth J, Thompson PD, et al. Pathophysiology of chorea and bradykinesia in Huntington's disease. Mov Disord. Li SH, Li XJ. Huntingtin and its role in neuronal degeneration. Factor SA, Friedman JH. The emerging role of clozapine in the treatment of movement disorders.

Kieburtz K. Antiglutamate therapies in Huntington's disease. J Neural Transm Suppl. Butler R, Bates GP. Histone deacetylase inhibitors as therapeutics for polyglutamine disorders.

Nat Rev Neurosci. Bonelli RM, Wenning GK. Pharmacological management of Huntington's disease: an evidence—based review. Curr Pharm Des. Stadtman ER. Role of oxidant species in aging. Curr Med Chem.

Lastres—Becker I, de Miguel R, De Petrocellis L, et al. J Neurochem. Fernandez—Ruiz J. The endocannabinoid system as a target for the treatment of motor dysfunction. Br J Pharmacol. Sherki Y. G, Melamed E, Offen D. Oxidative stress induced—neurodegenerative diseases: the need for antioxidants that penetrate the blood brain barrier.

P Pacher, JS Beckman, L Liaudet. Nitric oxide and peroxynitrite in health and disease. Physiol Rev. S Laganiere, BP Yu. Modulation of membrane phospholipid fatty acid composition by age and food restriction. A biologic clock: the mitochondria? J Am Geriatrics Society. P Larsen. Aging and resistance to oxidative damage in Caenorhabditis elegans.

Proc Natl Acad Sci U S A. LA MacMillan—Crow, JA Thompson. Peroxynitrite—mediated inactivation of manganese uperoxide dismutase involves nitration and oxidation of critical tyrosine residues.

Toxicology of the Human Environment — the critical role of free radicals. Taylor and Francis: London; F Krotz, HY Sohn, T Gloe, et al. Oxidase—dependent platelet superoxide anion release increases platelet recruitment. Abheri Das Sarma,m Buring JE, Peto R.

Antioxidant Vitamins Benefits Not Yet Proved editorial. International Journal of pharma Sciences and Research. Delanty N. Antioxidant Therapy in Neurologic Disease. Arch Neurol. Sies H. Oxidative stress: from basic research to clinical application. Am J Med.

Halliwell B, Gutteridge JM. Role of free radicals and catalytic metal ions in human disease: an overview. Methods Enzymol. Gao HM, Liu B, Zhang W, et al. Critical role of microglial NADPH oxidase—derived free radicals in the in vitro MPTP model of Parkinson's disease.

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Biochem Soc Trans. Gerlach M, Ben—Shachar D, Riederer P, et al. Altered brain metabolism of iron as a cause of neurodegenerative diseases?

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We Care About Your Privacy Upon reacting with ROS, GSH becomes a glutathione radical, which can be reconverted to its reduced form [ 54 ]. Meng B, Li J, Cao H. Clin Chim Acta — Ann NY Acad Sci. Cardoso, B. Does vitamin C influence neurodegenerative diseases and psychiatric disorders? No effect on cancer incidence, death from cancer, or the incidence of major cardiovascular events.
Significant Role of Free Radicals in Inflammation Discovery of potent telomerase activators: unfolding new therapeutic and anti-aging perspectives. Liguori, I. Rev 87, — For example, mitochondria-derived ROS has an impact on initial extracellular matrix contact, NOX-derived ROS are involved in invadopodia formation. Oxidized phospholipids, through receptor-mediated or receptor-independent pathways, can therefore then activate endothelial cells, induce endothelium adhesion molecules expression, attract monocytes, have endothelium cytotoxic effects, and increase proinflammatory gene activity and cellular growth factors Esper et al.
Understanding antioxidants - Harvard Health Reid, M. Self repair: The body also has systems to repair or replace damaged building blocks of cells. Critical role of microglial NADPH oxidase—derived free radicals in the in vitro MPTP model of Parkinson's disease. Herrera, B. J Pharmacol Sci — Regular exercise as a unique form of physiological stress is able to trigger adaptation, while autophagy, especially selective mitochondrial autophagy, also called mitophagy, allows for such cardiovascular adaptation Wu N.
Introduction

Correspondence: Firoz Khan, Department of Pharmaceutical Technology, Meerut Institute of Engineering and Technology, Meerut, N. H, Delhi-Roorkee Highway, Baghpat Bypass Road Crossing Meerut, U. P- , India. Received: May 14, Published: July 5, Citation: Khan F, Garg VK, Singh AK, et al.

J Anal Pharm Res. DOI: Download PDF. Antioxidants are the agents believed to quench the free radicals generation from an individual who start the stages of neurodegeneration. Free radicals are atoms that contain one or more unpaired electrons because of this property which makes them highly reactive.

Because of this property these free radicals attached very quickly on the defective cell or that area causes a micro crack in the mitochondrial cell, causes cell damage.

Oxidative free radicals are generated by metabolic reactions which can be creating a chain reaction with leading to membrane lipid per-oxidation and DNA damage at the cellular level in the neurons. Many endogenous and dietary compounds like vitamin E and C, superoxide dismutase, coenzyme Q 10 , ferritin, transferring, ceruloplasmin, α tocopherol, β carotene, α lipoate, lycopene and ascorbic acid have antioxidant and free radical scavenging properties that help to quench free radical in HD and delay the oxidative damage.

Antioxidant can be used to defense the mitochondrial damage and several mechanisms include removal of O 2 , scavenging of reactive oxygen and nitrogen species or their precursors, inhibition of ROS formation and binding of metal ions needed for the catalysis of ROS, generation and up-regulation of endogenous antioxidant defenses the tissue damage which can be beneficial in HD.

The present review deals with the effect of antioxidants on Huntington disease and certain antioxidants can be prepared by plant dietary fibers, fruits and some type of vegetables. Plants and polyphenols have the great role in the management of the symptoms of Huntington disease.

Keywords: huntington disease, antioxidants, reactive oxygen species, mitochondrial damage. Huntington's disease is an autosomal dominant neurodegenerative disease caused by a mutation in the gene encoding a protein called huntingtin htt.

The mutation consists in an excess of repeats in the CAG triplet within the coding region of the IT15 gene encoding htt, resulting in a polyQ tract near the N-terminus of this protein. motor abnormalities and cognitive impairment. protein misfolding, abnormal proteolysis, protein aggregation and deposition, transcriptional dysregulation, mitochondrial dysfunction, excitotoxic and oxidative events, and glial activation and local inflammatory events, have been also involved in neuronal death in HD.

They only have relief therapy to alleviate some symptomatic features associated to the disease i. antidopaminergic drugs to alleviate the hyperkinesia observed in the first stages. unsaturated fatty acids, minocycline, coenzyme Q10, inhibitors of histone deacetylases, have been studied in preclinical models and, even, some of them have entried in the clinical evaluation phase as potential novel disease-modifying agents in HD.

Great geographic differences were seen in HD prevalence. The overall prevalence of HD in Asian was 0. Recently, an epidemiologic study of HD in Taiwan China showed that the average annual incidence rate was 0.

Many studies have showed that HD prevalence is closely related to the different genotypes of population. The available information on the world distribution of Huntington's disease HD from population surveys and death rate analysis is summarized and discussed in the light of genetic studies.

It is concluded that most European populations, both Northern and Southern, show a relatively high prevalence 4—8 per , , and that the disorder may also be frequent in India and parts of central Asia.

HD is notably rare in Finland and in Japan, but data for Eastern Asia and Africa are inadequate. The disorder may have been underestimated in the American black population. Populations derived from recent European immigration show frequencies and origins of HD comparable to those expected from their own origins and expansion; there is no evidence to suggest that the HD gene has spread disproportionally and its selective effect may be close to neutral.

Multiple separate introductions of the gene have been the rule in large populations. Several major foci of HD exist as the result of rapid population expansion. It is likely that a number of separate mutations for HD will be shown to be responsible for the disease, but that the high frequency of HD in European populations will prove to be the result of one or a very small number of mutations, probably of great antiquity.

Free Radicals are molecules with an unpaired electron. Due to the presence of an unpaired free electron, these molecules are highly reactive. They are important intermediates in natural processes involved in cytotoxicity, control of vascular tone, and neurotransmission.

Radiolysis is a powerful method to generate specific free radicals and measure their reactivity. Stable radicals : The prime example of a stable radical is molecular oxygen O 2. Thiazyl radicals show remarkable kinetic and thermodynamic stability, with only a very limited extent of π resonance stabilization.

Persistent radicals: Compounds with persistent radicals are long lived due to steric crowding around the radical center and makes them physically difficult to react with another molecule.

Examples of these include-Gomberg's triphenylmethyl radical, Fremy's salt Potassium nitrosodisulfonate, Nitroxides, such as TEMPO 2,2,6,6-Tetramethylpiperidineoxyl , verdazyls, nitronyl nitroxides, azephenylenyls, radicals derived from PTM perchlorophenylmethyl radical and TM tris 2,4,6-trichlorophenylmethyl radical.

The longest-lived free radical is melanin, which may persist for millions of years. Diradicals: Molecules containing two radical centers are called diradical. Multiple radical centers can also exist in a molecule.

Molecular oxygen naturally i. atmospheric oxygen exists as a diradical in its ground state as triplet oxygen. The high reactivity of atmospheric oxygen is owed somewhat to its diradical state although non-radical states of oxygen are actually less stable.

The existence of atmospheric molecular oxygen as a triplet-state radical is the cause of its paramagnetic character, which can be easily demonstrated by attraction of oxygen to an external magnet. The basic causes include the following. Normally, bonds do not split to leave a molecule with an odd and an unpaired electron.

But when weak bonds split, free radicals are formed. Free radicals are very unstable and react quickly with other compounds, trying to capture the needed electron to gain stability. When the "attacked" molecule loses its electron, it becomes a free radical itself, beginning a chain reaction.

All this happens in nanoseconds. Once the process is started, it can cascade, finally resulting in the disruption of a living cell.

Normally, the body can handle free radicals, but if antioxidants are unavailable, or if the free radical production becomes excessive, damage can occur. In chemistry, free radicals take part in radical addition and radical substitution as reactive intermediates.

Chain reactions involving free radicals can usually be divided into three distinct processes:. Initiation reactions are those, which result in a net increase in the number of free radicals. They may involve the formation of free radicals from stable species or they may involve reactions of free radicals with stable species to form more free radicals.

Propagation reactions involve free radicals in which the total number of free radicals remains the same. Termination reactions are those reactions resulting in a net decrease in the number of free radicals. The formation of radicals may involve breaking of covalent bonds homolytically, a process that requires significant amounts of energy.

The bond energy between two covalently bonded atoms is affected by the structure of the molecule. Homolytic bond cleavage most often happens between two atoms of similar electronegativity. However, propagation is a very exothermic reaction.

Radicals may also be formed by single electron oxidation or reduction of an atom or molecule. An example is the production of superoxide by the electron transport chain. Peroxidation of lipids in cell membranes can damage cell membranes by disrupting fluidity and permeability.

Lipid peroxidation can also adversely affect the function of membrane bound proteins such as enzymes and receptors. Direct damage to proteins can be caused by free radicals. This can affect many kinds of protein, interfering with enzyme activity and the function of structural proteins.

Fragmentation of DNA caused by free radical attack causes activation of the poly ADP-ribose synthetase enzyme. The site of tissue damage by free radicals is dependent on the tissue and the reactive species involved.

Extensive damage can lead to death of the cell; this may be by necrosis or apoptosis depending on the type of cellular damage.

When a cell membrane or an organelle membrane is damaged by free radicals, it loses its protective properties. This puts the health of the entire cell at risk. Cells normally defend themselves against ROS damage through the use of enzymes such as superoxide dismutase and catalase.

Small molecule antioxidants such as ascorbic acid vitamin C , uric acid, and glutathione also play important roles as cellular antioxidants. Similarly, polyphenol antioxidants assist in preventing ROS damage by scavenging free radicals.

The negative effects of ROS on cell metabolism include roles in programmed cell death and apoptosis, whereas positive effects include induction of host defense genes and mobilization of ion transport systems.

In particular, platelets involved in wound repair and blood homeostasis release ROS to recruit additional platelets to sites of injury. These also provide a link to the adaptive immune system via the recruitment of leukocytes. Reactive oxygen species are involved in cardiovascular disease, hearing impairment via cochlear damage induced by elevated sound levels, ototoxicity of drugs such as cisplatin, and in congenital deafness in both animals and humans.

Reactive oxygen species ROS are very small molecules and are highly reactive due to the presence of unpaired valence shell electrons.

ROS is formed as a natural byproduct of the normal metabolism of oxygen and have important roles in cell signaling. However, during times of environmental stress ROS levels can increase dramatically, which can result in significant damage to cell structures. Platelets involved in wound repair and blood homeostasis release ROS to recruit additional platelets to sites of injury.

Generally, harmful effects of reactive oxygen species on the cell are most often like -Damage of DNA, oxidations of polydesaturated fatty acids in lipids, oxidations of amino acids in proteins, oxidatively inactivates specific enzymes by oxidation of co-factors Table 1.

Transferin iron Vitamin C, Ferritin iron beta-carotene, Myoglobin iron. Thiols GSH, Lipoic acid, N-acetyl cysteine NADH and NADPH Ubiquinone. Table 1 Reactive oxygen species and their corresponding neutralising antioxidants and also additional antioxidants These are the list of antioxidants that help to include in the diet and manage to scavenge the free radical that can develop the steps of neurodegeneration.

All aerobic forms of life maintain elaborate anti-free-radical defense systems, also known as antioxidant systems. Enzymes: The defense enzyme, superoxide dismutase SOD , takes hold of molecules of superoxide—a particularly destructive free radical-and changes them to a much less reactive form.

SOD and another important antioxidant enzyme set, the glutathione system, work within the cell. Self repair: The body also has systems to repair or replace damaged building blocks of cells.

Most protein constituents in the cell are completely replaced every few days. Scavenger enzymes break used and damaged proteins into their component parts for reuse by the cell. Nutrients: Vitamins and other nutrients neutralize the oxy radicals' and serves as second line of defense. Among the many substances used are Vitamins C and E, beta-carotene, and bioflavonoids.

Free radical or oxidative injury may be a fundamental mechanism underlying a number of human neurologic diseases. OS can cause cellular damage and subsequent cell death because the reactive oxygen species ROS oxidize vital cellular components such as lipids, proteins, and DNA.

Therapy using free radical scavengers antioxidants has the potential to prevent, delay, or ameliorate many neurologic disorders. However, the biochemistry of oxidative pathobiology is complex, and optimum antioxidant therapeutic options may vary and need to be tailored to individual diseases.

The body generates free radicals in response to environmental insults, such as tobacco smoke, ultraviolet rays, and air pollution, but they are also a natural byproduct of normal processes in cells.

When the immune system musters to fight intruders, for example, the oxygen it uses spins off an army of free radicals that destroy viruses, bacteria, and damaged body cells in an oxidative burst.

Some normal production of free radicals also occurs during exercise. This appears to be necessary in order to induce some of the beneficial effects of regular physical activity, such as sensitizing your muscle cells to insulin. Because free radicals are so pervasive, you need an adequate supply of antioxidants to disarm them.

Your body's cells naturally produce some powerful antioxidants, such as alpha lipoic acid and glutathione. The foods you eat supply other antioxidants, such as vitamins C and E.

Plants are full of compounds known as phytochemicals—literally, "plant chemicals"—many of which seem to have antioxidant properties as well. For example, after vitamin C has "quenched" a free radical by donating electrons to it, a phytochemical called hesperetin found in oranges and other citrus fruits restores the vitamin C to its active antioxidant form.

Carotenoids such as lycopene in tomatoes and lutein in kale and flavonoids such as flavanols in cocoa, anthocyanins in blueberries, quercetin in apples and onions, and catechins in green tea are also antioxidants.

News articles, advertisements, and food labels often tout antioxidant benefits such as slowing aging, fending off heart disease, improving flagging vision, and curbing cancer. And laboratory studies and many large-scale observational studies those that query people about their eating habits and supplement use and then track their disease patterns have noted antioxidant benefits from diets rich in them, particularly those coming from a broad range of colorful vegetables and fruits.

But results from randomized controlled trials of antioxidant supplements in which people are assigned to take specific nutrient supplements or a placebo have not supported many of these claims.

Indeed, too much of these antioxidant supplements won't help you and may even harm you. It is better to supply your antioxidants from a well-rounded diet. To learn more about the vitamins and minerals you need to stay healthy, read Making Sense of Vitamins and Minerals , a Special Health Report from Harvard Medical School.

As a service to our readers, Harvard Health Publishing provides access to our library of archived content. Please note the date of last review or update on all articles. No content on this site, regardless of date, should ever be used as a substitute for direct medical advice from your doctor or other qualified clinician.

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Select Oral health language of raducals to view the total content in your radicalx language. Role of free radicals and Antioxidants in Medical Science received citations as per google scholar report. Ibrhim Eiz, Department of Biochemistry, University of Tehran, Tehran, Iran, Email: ibrzie gmail. Received: Aug, Manuscript No. EJMOAMS- ; Editor assigned: Aug, Pre QC No.

Role of free radicals -

Another important class of enzymatic peroxide scavenger is PRDX. Six different classes of PRDX have been identified Poole and Nelson, , showing either one 1-Cys PRDX or two 2-Cys PRDX redox-active cysteine residues Park et al. The PRDX catalytic cycle involves H 2 O 2 decomposition and the subsequent regeneration of the resting enzyme, using a small cysteine protein thioredoxin Trx as the reductant reactions 8 and 9.

Trx shows two vicinal cysteines in the typical CXXC motif , forming, in turn, a disulfide internal bridge upon oxidation. In the case of PRDX6 isoform, Trx can be replaced by GSH. All the enzymatic activities described above rely on the continuous regeneration of the reduced form of reductants mainly GSH and Trx.

This is usually performed by some reductases, NADPH-dependent such as glutathione reductase E. However, as shown in Figure 2 , reduced NADPH is, in turn, needed by these reductases for their continuous action.

So, enzymes responsible for the constant NADPH production can be considered secondary antioxidants, as their misfunction could affect the whole ROS balance. The main NADPH metabolic source is the pentose phosphate pathway, through the first two enzymatic activities: glucosephosphate dehydrogenase E.

However, other contributions come from the malic enzyme E. Some chemical molecules of low-molecular-weight can also directly act as antioxidants. In this case, their action is not catalytic, always needing antioxidant regeneration or its supply from the diet.

Non-enzymatic antioxidants can therefore be divided into endogenous if the eukaryotic cell is able to synthesize it and exogenous if the antioxidant needs to be ingested mandatorily through the diet.

GSH γ-glutamyl-cysteinyl-glycine, Figure 4 is a tripeptide, mainly distributed in cytosol, but also in nuclei, peroxisomes and mitochondria. Despite being ubiquitous, the liver is the leading site for its synthesis Banafsheh and Sirous, GSH biosynthesis is an endergonic process ATP hydrolysis is coupled , in which firstly glutamate and cysteine condense to yield γ-glutamylcysteine reaction catalyzed by glutamate-cysteine ligase, E.

This unusual γ-peptidic bond protects it from the common peptidases action. In the final step, GSH synthetase E. Figure 4. Glutathione GSH , a tripeptide with an active —SH function.

GSH undergoes a redox cycle, dimerizing with a disulfide bridge formation. α-Lipoic acid 1,2-dithiolanepentanoic acid, Figure 4 is a disulfide compound that undergoes a redox cycle similar to GSH. Accordingly, it scavenges reactive ROS, and regenerate vitamins C and E, and GSH in their active forms Kucukgoncu et al.

Lipoic acid also has a role in metal chelation, preventing Fenton-like radical reactions Zhang and McCullough, Nevertheless, even small proteins, such as Trx and glutaredoxin can similarly function as thiol antioxidants, showing redox-active mono- or di-cysteine motif CXXC.

Both proteins can be in turn reduced back to their active form, directly by GSH or indirectly by NADPH Banafsheh and Sirous, Melatonin N -acetylmethoxytryptamine, Figure 5 is a neurohormone derived from amino acid tryptophan. It is involved in circadian rhythms but also acts as a potent antioxidant, protecting cell membranes against lipid peroxidation Beyer et al.

It has been described to be more effective in ROS scavenging than vitamin E, GSH, vitamin C and β-carotene Watson, Coenzyme Q10 or ubiquinone 2,3-dimethoxymethylpolyisoprene parabenzoquinone, Figure 5 is an isoprenoid antioxidant present in cell membranes, essential for ETC Tafazoli, Its synthesis starts from oligomerization of isoprenoid building blocks, isopentenyl pyrophosphate and dimethylallyl pyrophosphate both arising from the mevalonate pathway and the key enzyme 3-hydroxymethyl-glutaryl-CoA reductase E.

The resulting decaprenyl diphosphate is then conjugated with a tyrosine derivative to yield the active form of the coenzyme. It is one of the few liposoluble antioxidants, ensuring lipoproteins and lipids protection from radical chain reactions, peroxidation and oxidative damage Lee et al.

In its active form quinol , coenzyme Q10 can scavenge several ROS or regenerate other oxidized antioxidants including vitamins C and E.

In turn, the quinone form can be reduced back by several NAD P H-dependent enzymatic systems. Exogenous antioxidants need to be supplemented continuously through the diet since their synthetic pathways are usually present only in microbial or plant cells.

Vitamins, two of which show prominent antioxidant effects, such as vitamins C and E, belong to essential class of molecules. Vitamin C ascorbic acid exists in two redox forms: ascorbic acid AA is the reduced form, which is deprotonated at physiological pH thus, occurring in its anion form, ascorbate.

Due to its high electron-donating power, AA can undergo two-electron oxidation, yielding dehydroascorbic acid DHA.

One-electron oxidation of AA is also possible, generating a semi-dehydro-ascorbyl radical Kocot et al. DHA can be regenerated to the active AA form by GSH- or Trx-dependent mechanisms. Humans do not express the enzyme L -gulonolactone oxidase E. Thus, AA must be ingested by food or supplements , particularly tomatoes, pineapples, watermelons and all citrus fruits Banafsheh and Sirous, AA effectively quenches ROS, both directly and cooperatively regenerating oxidized vitamin E, GSH, and carotenoids.

Vitamin E is a fat-soluble vitamin, mostly found in several vegetable oils, nuts, broccoli and fish. Eight different forms have been reported α-, β-, γ-, and δ-tocopherol, and α-, β-, γ-, and δ-tocotrienol , but α-tocopherol has the highest antioxidant activity, especially in cell membranes Salehi et al.

A variously methyl-substituted chromanol ring characterizes tocopherols. A long phytyl chain gives the hydrophobicity Figure 6. Figure 6. Chemical structures of Vitamin C, Curcumin, Resveratrol, Quercetin, Vitamin E, β-carotene, Lycopene. On the contrary, tocotrienols bear an unsaturated isoprenoid chain.

α-Tocopherol is able to undergo hydrogen transfer to several ROS, including 1 O 2 , superoxide anion and peroxyl radicals. The oxidized and radical derivative of vitamin E is then reduced by the AA.

Carotenoids are a broad class of tetraterpenes, widely distributed among plants. Carotenes are also vitamin A precursors. Carotenoids protect plant chlorophyll, acting as accessory pigments during photosynthesis.

Thus, they are intensely colored red, orange, or yellow molecules. Carotenoids have been suggested to be chemopreventive agents in cancer Marti et al. Their biological activities also include ROS scavenging Hernández-Almanza et al.

β-Carotene comprises one of the most diffused carotenes, being the primary pro-vitamin A precursor, and it is found mainly in carrots, pumpkins, mangoes and apricots. Lycopene is another well-known acyclic carotene, not being a precursor of vitamin A, and is found primarily in tomatoes and other red fruits, but not in strawberries and cherries.

Indeed, carotenoids are strong ROS scavengers, operating a very particular physical and chemical 1 O 2 quenching Banafsheh and Sirous, In the physical mechanism, the carotenoid electron-rich structure absorbs 1 O 2 excess energy, reaching an excited state.

The conjugated double bond structure in carotenoids is responsible for this ability. The excited state then decays to the ground state, losing the surplus energy as heat. During this cycle, the structure of this molecule stays unchanged. Polyphenols are a large class of plant secondary metabolites, whose synthesis is usually possible only in these organisms Sanjust et al.

The key enzyme [phenylalanine ammonia-lyase PAL , EC 4. PAL catalyzes the non-oxidative deamination of phenylalanine to trans -cinnamic acid, which is the fundamental building block for polyphenol synthesis in the phenylpropanoid pathway Ertani et al.

Several biological functions have been ascribed to polyphenols, including anti-inflammatory, antioxidant, antimicrobial and antimelanogenesis effects Zucca et al.

For instance, one of the most studied polyphenols has been curcumin, gaining a lot of attention also for nutraceutical applications. Curcumin can also increase GSH cellular levels Banafsheh and Sirous, Epigallocatechingallate EGCG is a well-known antioxidant.

The green tea catechins include catechin, epicatechin, epigallocatechin, epicatechin gallate, and epigallocatechin gallate Barbieri et al. Flavonoids, in addition to its strong antioxidant properties, quench ROS formation inhibiting several enzymes and chelating metals involved in radical chain reactions Banafsheh and Sirous, Furthermore, flavonoids can also affect free metal ion concentrations.

Indeed, flavonoids have the well-known capacity to chelate several metal ions such as iron and copper , blocking free radical generation Kumar and Pandey, For instance, quercetin is one of the most diffused flavonols present in broccoli, apples, grapes, onions and soybeans, with both iron-chelating and iron-stabilizing abilities Kumar and Pandey, On the other hand, catechol and galloyl-derivatives are generally well-known metal chelators Jomova and Valko, So, they can all exert their antioxidant activity by blocking Fenton-like reactions.

Organosulfur compounds have also been suggested as potent antioxidants. The most studied are probably some sulfur-containing metabolites present in garlic mainly S -allyl-mercapto cysteine, S -allyl cysteine, and diallyl sulfide, diallyl trisulfide Kimura et al.

These organosulfur are also responsible for typical garlic flavor. Their antioxidant actions include scavenging ROS and inhibiting lipids peroxidation Borek, ; Miltonprabu et al.

Several minerals, in small amounts, are also essential for some enzymatic antioxidant activities. They are therefore sometimes regarded as antioxidants themselves. For instance, selenium is a necessary component of GPX Battin and Brumaghim, , while copper, zinc, and manganese are fundamental for SOD activity.

The balance between ROS production and purification maintains homeostasis of the body, but is most often directed to the formation of free radicals and involvement in the pathophysiology of chronic diseases. The use of antioxidant supplements containing multivitamins and minerals has always grown in popularity among consumers.

But some recent studies have not shown any beneficial effect of antioxidant therapy. Oxidative stress has a dual character: it is both harmful and beneficial to the body, because some ROS are signaling molecules on cellular signaling pathways.

Lowering the level of oxidative stress through antioxidant supplements is therefore not beneficial in such cases Ye et al.

Antioxidants are also prone to oxidation since oxidation and reduction reactions do not happen in isolation. AA, a potent antioxidant, mediates several physiological responses.

This reaction is responsible for oxidative stress-produced DNA damage. However, the role of AA as anti- or pro-oxidant depends on the dose used, as observed in the case of ischemia-induced oxidative stress Seo and Lee, With increased oxygen tension, carotenoids tend to lose their antioxidant potential.

Otherwise, α-tocopherol, a powerful antioxidant, becomes pro-oxidant at high concentrations Cillard and Cillard, Interestingly, when it reacts with a free radical, it becomes a radical in itself. If there is not enough AA for its regeneration, it will remain in that highly reactive state Lü et al.

Flavonoids can also act as pro-oxidants depending on the concentrations used Prochazkova et al. Nevertheless, the extent to which these phytochemicals are capable of acting as anti- or pro-oxidants in vivo is still poorly understood, and this topic undoubtedly requires further research.

The hypothesis that antioxidants could protect against cancer because they can neutralize reactive oxygen species ROS that can damage DNA has long been issued.

In laboratory and animal studies, the presence of elevated levels of exogenous antioxidants has been shown to prevent the types of free radicals that have been associated with the development of cancer.

A few randomized studies evaluating the role of antioxidant supplements for cancer prevention were conducted in collaboration with the National Cancer Institute Goodman et al.

No data were obtained to justify that they are effective in primary cancer prevention. An analysis in the United States concluded that there is no clear scientific evidence for the benefits of vitamin and mineral supplements in cancer prevention.

It is important to point out that there have been cases where people who have resorted to these types of supplements have encountered an unfavorable evolution of the disease. Preclinical studies also report that antioxidants have contributed to the expansion of tumor processes in animal models.

A well-known case is that of vitamin A, for which the administration of high doses in supplements has been associated with an increased risk of cancer. Vitamin A can be obtained preformed from animal sources or plant products, derived from β-carotene.

β-Carotene is an orange pigment found in fruits and vegetables carrots, sweet potatoes, mangoes, apricots , and in the body it is converted to vitamin A. A normal intake has a beneficial effect against the risk of cancer.

However, studies have shown a correlation between the administration of β-carotene supplements and the risk of bladder cancer, as well as the risk of lung cancer in smokers Lin et al. In another study, the administration of α-tocopherol and β-carotene for lung cancer did not change the incidence of lung cancer.

However, α-tocopherol supplements have been shown to be effective in prostate cancer whose incidence is reduced Goodman et al.

A trial evaluated the effectiveness of long-term supplementation with vitamin E and vitamin C in the risk of developing cancer. One of the findings of the study was that these types of supplements do not reduce the risk of prostate cancer or the overall risk of cancer in men of middle age or older.

No significant results were obtained regarding the risk of colorectal or lung cancer Gaziano et al. Vitamin E and C supplements showed poor results in many studies. There was a reduction in cardiovascular mortality, but no significant effect was observed on overall mortality. The authors concluded that vitamin E supplementation for the prevention of cardiovascular disease among healthy women is not justified.

Moreover, cancer mortality is not significantly influenced by vitamin E supplementation Lee et al. The Selenium and Vitamin E Cancer Prevention Trial SELECT which included over 35, men over the age of 50, showed that selenium and vitamin E supplements do not prevent prostate cancer.

This article summarizes the evidence from a large number of meta-analyzes covering the pathophysiological impact of antioxidants on the most common chronic diseases. The main criticism of the review is that the data were extracted from meta-analyzes and not from individual studies, but this can be considered an advantage because meta-analyzes provide the highest degree of evidence.

In the case of antioxidants, studies show that more does not necessarily mean better. Consuming superfoods does not compensate for other unhealthy eating habits or an unbalanced lifestyle.

Free radicals, as well as antioxidants, can have beneficial effects on the body. Therefore, we are talking about a balance and not a negative role attributed to free radicals and a positive one to antioxidants. Degradation of nucleic acids, proteins, lipids or other cellular components are among the effects that an excessive concentration of free radicals can generate.

Risk factors leading to free radicals include air pollution, ionizing radiation, prolonged exercise, infections, excessive consumption of polyunsaturated fatty acids Poprac et al. On the other hand, antioxidants are considered to be the solution to these problems — substances that neutralize free radicals.

In some situations, some substances act as antioxidants, in other situations they become prooxidants, depending on the chemical composition of the environment in which they are.

There are many types of antioxidants, and the role in the body and the mechanisms by which they act are different. One misconception is that one antioxidant can be replaced with another, having the same effect. In fact, each has its own unique biological properties Chen X.

There is also a significant difference between taking antioxidants from food and administering an isolated substance as a supplement. Many substances that demonstrate beneficial effects in the laboratory do not work when introduced into the human body.

Many antioxidants do not have good bioavailability. The concentration of antioxidants such as polyphenols is sometimes so low in the blood that no significant effect is observed Fernández-García et al. Fruits and vegetables contain bioactive substances that in many cases do not work as antioxidants if we consider them outside of the body.

But they work as antioxidants when they are in the body, because they activate their own antioxidant mechanisms. These bioactive substances are the secret behind vegetable consumption Kurutas, Antioxidant supplements may have different health benefits.

On the one hand, it is possible that other substances present in food are responsible for the positive effects on health, not necessarily a certain type of antioxidant, but the synergistic effect of several substances. On the other hand, the chemical structure of antioxidants in food is often different from that identified in supplements.

An example is vitamin E. There are eight variants of vitamin E in the foods we eat, while the supplements used in most studies contain only one form Firuzi et al.

Studies also frequently include healthy people, for whom oxidative stress on the body is not significant to determine a risk of disease. Antioxidants can benefit certain categories of patients in whom there is a real, documented imbalance, but it may not bring anything extra for a person who gets a sufficient amount of nutrients from their diet.

Observational studies analyze the trends, or habits of certain large population groups. In many, all the risk factors that could influence the course of the study can be controlled, and demonstrating a cause-effect relationship is difficult.

We also cannot rely on small studies, carried out over a short period of time and using very concentrated substances extracted from different plant or animal products, to say that we have a superfood.

Nutrition is a complex science, and at the moment we can only rely on the evidence accumulated so far. A food rich in antioxidants will not compensate for an unhealthy lifestyle.

Oxidative stress can be reduced by approaching a balanced lifestyle. Nutrition plays a critical role, and the best treatment against oxidative stress is antioxidants. Oxidative stress plays an important role in the pathogenesis of potentially severe conditions.

In the long term, increasing the level of prooxidant factors can cause structural defects in mitochondrial DNA and alterations in enzymatic functionality or cellular structures, with the appearance of functional, structural abnormalities or aberrations in gene expression. It has also been shown that in addition to metabolic products, other external agents can have a prooxidant effect, which has led to the conclusion that lifestyle and diet can play an important role in controlling oxidative stress.

Plant-derived bioactive molecules have gained pivotal attention in recent years, given their therapeutic relevance in both disease prevention and treatment, whether using the whole plants, plant extracts or even the isolated constituents with full phytochemical profiles.

The daily intake of a wide variety of phytochemicals has shown to be chemopreventive. It might hold promise for add-on treatment for several diseases, including cancer, diabetes, cardiovascular disease and neurodegenerative disorders. Larger randomized trials are needed to obtain clear scientific evidence on the benefits or risks of antioxidant supplementation during cancer treatment.

Antioxidants are also prone to oxidation, and therefore their use as foods or supplements should be carefully considered because oxidation and reduction reactions do not happen in isolation. The intake of high doses of antioxidants has been increasingly highlighted since there is increasing evidence of some detrimental effects.

The study of their chemical components as future prophylactic and therapeutic agents would be of particular interest, as they are more effective and safer than those widely available. In conclusion, oxidative stress is an important pathogenetic link for humans and studies in this field may be important elements in the future, to better understand and manage various diseases.

JS-R and MS-R contributed to the conceptualization. NA, PZ, EV, and LD contributed to the validation investigation. EP, JR, PT, EA, IP, YE, and MB contributed to the resources. AP, MN, and AD: data curation. MS-R, AD, LP, MI, NM, MM, WS, DC, WC, and JS-R contributed to the review and editing.

All authors contributed to the writing of the manuscript. All authors read and approved the final manuscript and contributed equally to the manuscript. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Cancer 69, — Forman, H. Reactive oxygen species and cell signaling: respiratory burst in macrophage signaling. Moreover, therapy with antioxidants may need to be given early in chronic insidious neurologic disorders to achieve an appreciable clinical benefit.

Pre-disease screening and intervention in at-risk individuals may also need to be considered in the near future. Oxidative stress is a general term used to describe a serious imbalance between the production of reactive oxygen species ROS and reactive nitrogen species RNS on the one hand, and the levels of antioxidant defences on the other.

Any prolonged imbalance results in oxidative damage to cells, tissues, and organs. External sources of ROS include radiation, UV light, chemical reagents, pollution, cigarette smoke, drugs of abuse, and alcohol.

At low or moderate levels, ROS and RNS exert beneficial effects on cellular responses and immune function. However, at high concentrations, they cause oxidative stress, and subsequent damage to proteins, lipids, and DNA.

Why the need of the free radical in neurodegeneration: The harmful effects of ROS cause damage to macromolecules such as proteins, lipids, polysaccharides or nucleic acids, are termed oxidative stress.

The intrinsic properties of neurons make them highly vulnerable to the detrimental effects of ROS: high metabolic rates; a rich composition of fatty acids prone to peroxidation; high intracellular concentrations of transition metals, capable of catalyzing the formation of reactive hydroxyl radicals; low levels of antioxidants; and reduced capability to regenerate.

Neurons have intense energy demands which are met by mitochondria. Mitochondria are both targets and important sources of ROS. It has been shown that oxidative stress stimulates mitochondrial fission; the addition of hydrogen peroxide to cultured cerebellar granule neurons induced mitochondrial fragmentation within one hour of treatment.

It was also shown that nitric oxide causes increased mitochondrial fission in neurons, prior to the onset of neuronal loss in a mouse model of stroke. On the other hand, expression of Mfn or a dominant negative Drp1 in cultured neurons, was protective against oxidative insults.

The generation of ROS appears to be increased in damaged mitochondria, and in cells with compromised mitochondrial function.

Oxidative stress within mitochondria can lead to a vicious cycle in which ROS production progressively increases leading, in turn, to progressive augmentation of damage.

Nucleic acid oxidation occurs in neurons during disease and is detected as elevated levels of 8-hydroxydeoxyguanosine 8-OHDG in DNA and 8-hydroxyguanosine in RNA. Hydroxyl radical-mediated DNA damage often results in strand breaks, DNA-protein crosslinking, and base-modifications.

All of these events can lead to neuronal injury. It is known that generation of ROS results in an attack not only on DNA, but also on other cellular components involving polyunsaturated fatty acid residues of phospholipids, which are extremely sensitive to oxidation.

Once formed, peroxyl radicals ROO· can be rearranged via a cyclisation reaction to endoperoxides precursors of malondialdehyde with the final product of the peroxidation process being malondialdehyde MDA. The major aldehyde product of lipid peroxidation other than malondialdehyde is 4-hydroxynonenal HNE.

Increased production of ROS also results in protein oxidation. Oxidation of cysteine residues may lead to the reversible formation of mixed disulfides between protein thiol groups —SH and low molecular weight thiols, in particular glutathione GSH, S-glutathiolation.

The concentration of carbonyl groups, generated by many different mechanisms is a good measure of ROS-mediated protein oxidation. The generation of isoprostanes has been shown to be a sensitive measure of lipid peroxidation, which are increased in cerebrospinal fluid CSF of HD patients.

ROS are often present in brain regions affected by neurodegenerative diseases. Studies in both HD patients and experimental models of HD support a role for oxidative stress and ensuing mitochondrial dysfunction in mediating the neuronal degeneration observed in HD.

Oxidative damage in HD has been previously reviewed in detail. The accumulation of ROS in neurons, and subsequent oxidative stress are attenuated by free radical scavengers, which can be categorized as enzymatic or non-enzymatic antioxidants.

Enzymatic antioxidants constitute one of the defense mechanisms against free radicals. These include superoxide dismutase SOD , glutathione peroxidase Gpx and catalase CAT. Non-enzymatic antioxidants are represented by ascorbic acid Vitamin C , α-tocopherol Vitamin E , glutathione GSH , retinoic acid, carotenoids, flavonoids, and other antioxidants.

The therapeutic approaches tested in vitro or in toxin or transgenic models of HD are given below-. As we know that neurodegenerative disorders is an important source of morbidity and mortality in human mankind.

Free radical involvement offers a novel therapeutic target in the management of Huntington diseases. However, it will happen only if the mechanism of action of the free radical can be understood properly. The antioxidant therapy can be used over the free radical generation and target the free radical that are responsible for the neurodegeneration such as HD.

Free-radical-mediated oxidative injury plays a major role in the defection of various diseases and trauma; chronic neurogenic and other neurodegeneration disease can be recognized. We know that oxygen is an essential molecule for survival of majority of living organisms in the world as well as the inside the body.

Oxidative stress mostly a harmful condition that occurs when there is an excess of free radicals will be generated or a decrease in antioxidant levels in the body. So, this review suggests the use of antioxidants to manage the disease state. Antioxidants quench oxidative stress by 1working to off-pair free radical generation and stopping them from starting the chain reactions that contribute to develop Huntington disease.

Oxidative stress OS has been responsible in the pathophysiology of various life threatening starts disease such as neurological and neurodegenerative diseases. Oxygen Species generally a free radical species can cause cellular damage and subsequent cell death because the reactive oxygen species which oxidize sensitive cellular components that makes a major part of proteins, lipids, ribose sugar and genetic material.

However, the excitatory amino acid glutamate is the major amino acid that can prevent such kind of neurodegeneration that are responsible for Huntington disease populations that are at high risk, such as elderly and newly diagnosed patients.

In this review we have to find the new way and the use of certain antioxidants to remove the wastes of free radical generation and scavenging properties of the antioxidants to manage in the disease and cure them. This is an open access article distributed under the terms of the, which permits unrestricted use, distribution, and build upon your work non-commercially.

About Us Paper Submission FAQs Testimonials Videos Reprints Pay Online Article Processing Charges Contact Us Sitemap. Home Open Access Journals eBooks Information For Author Article Processing Charges. Publication Ethics. Peer Review System. Behavioral Sciences Food and Nutrition Trends Global Trends in Pharmaceutical Sciences.

Home JAPLR Role of free radicals and certain antioxidants in the management of huntingtons disease a review. Journal of. Review Article Volume 7 Issue 4. Types of long lived radicals Stable radicals : The prime example of a stable radical is molecular oxygen O 2.

Formation of free radicals Normally, bonds do not split to leave a molecule with an odd and an unpaired electron. Chain reactions involving free radicals can usually be divided into three distinct processes: Initiation, Propagation, Termination.

Lipids Peroxidation of lipids in cell membranes can damage cell membranes by disrupting fluidity and permeability. Proteins Direct damage to proteins can be caused by free radicals.

DNA Fragmentation of DNA caused by free radical attack causes activation of the poly ADP-ribose synthetase enzyme. Oxidative stress Oxidative stress is a general term used to describe a serious imbalance between the production of reactive oxygen species ROS and reactive nitrogen species RNS on the one hand, and the levels of antioxidant defences on the other.

The therapeutic approaches tested in vitro or in toxin or transgenic models of HD are given below- In vitro studies Metalloporphyrins, metal-containing catalytic antioxidants, have emerged as a novel class of potential therapeutic agents that scavenge a wide range of reactive oxygen species.

A manganese porphyrin has been reported to significantly reduce cell death in an in vitro chemical model of HD. Treating cultured rodent cortical neurons with glutamate resulted in significant neurodegeneration, which was completely rescued with ascorbic acid co-treatment.

Using a neuronal cell-based assay, glutamate-induced neuronal death was significantly attenuated in a dose-dependent manner by α-tocopherol.

Also, treatment with idebenone in this in vitro model resulted in complete neuroprotection in a dose-dependent manner.

Melatonin significantly reduced DNA damage and improved neuronal survival. In another study using the 3-NP model of HD, melatonin treatment significantly ameliorated the increase in lipid peroxidation, protein carbonyls and SOD activity within the striatum.

Selenium dose-dependently reduced lipid peroxidation and significantly improved neuronal morphology within the striatum of rats treated with quinolinic acid, an N-methyl-D-aspartate antagonist that results in striatal neurodegeneration.

Creatine also buffers intracellular energy reserves through its intermediate, phosphocreatine PCr ; stabilizes intracellular calcium; and inhibits activation of the mitochondrial transition pore.

Creatine supplementation significantly reduces striatal lesion volumes produced by the neurotoxins 3-NP and malonate. The antioxidant compound CoQ10 also demonstrated efficacy in murine models of HD.

CoQ10, ubiquinone, is a lipid-soluble benzoquinone which, when reduced to ubiquinol, which possesses significant antioxidant potential. In addition, CoQ10 can induce increases in vitamin E, enhancing its antioxidant capacity.

Using the mitochondrial toxins malonate. FK also known as Tacrolimus or Fujimycin is an immunosuppressive drug mainly used to lower allograft rejection and also in topical preparations. Recently, the neuroprotective effects of FK were reported in 3-NP model of HD.

FK treatment significantly reduced behavioral deficits, MDA levels, nitrite concentration, and restored antioxidant enzyme levels of SOD and catalase, and levels of dopamine and norepinephrine in the striatum, cortex, and hippocampus.

Lycopene, a carotenoid pigment and phytochemical naturally found in fruits and vegetables, reduced oxidative stress markers and improved behavior in a 3-NP induced rodent model of HD.

In transgenic mouse models of HD Lipoic acid is an essential cofactor for many enzyme complexes and is present in mitochondria as the cofactor for pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase.

It is an effective antioxidant and has been used to treat disease associated with impaired energy metabolism. Pyruvate plays a major role in glycolysis, and also possesses significant antioxidant capacity.

Creatine exists in the cell both as free creatine and phosphocreatine PCr which together comprise the total creatine pool. In tissues with high energy requirements such as skeletal muscle and brain, PCr serves as a short term energy buffer in which adenosine diphosphate is phosphorylated to adenosine triphosphate.

This phosphorogroup transfer is catalyzed by the important creatine kinase CK enzyme. It is effective in preventing cell membrane damage caused by reactive oxygen species. Recently, administration of a relatively high dose of L-carnitine to NQ transgenic mice was shown to extend the survival, ameliorate motor performance, and decrease the number of intranuclear aggregates.

Synthetic triterpenoids, which are analogues of 2-Cyano-3, Dioxooleana-1,9-DienOic acid CDDO , are of great interest because of their antioxidant and anti-inflammatory properties.

Triterpenoids significantly preserved the striatal volumes of the NQ mice, by preventing the atrophy of the medium spiny neurons, and they rescued behavioral deficits, extended survival, attenuated peripheral pathology, and reduced 8-OHdG, MDA and 3-nitrotyrosine immune-reactivity in the striatum.

The Huntington's Disease Collaborative Research Group. A novel gene containing a rinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Ross CA, Tabrizi SJ. Huntington's disease: from molecular pathogenesis to clinical treatment. Lancet Neurol. Roze E, Bonnet C, Betuing S, et al.

Huntington's disease. Adv Exp Med Biol. Rosas HD, Salat DH, Lee SY, et al. Complexity and heterogeneity: what drives the ever—changing brain in Huntington's disease? Ann NY Acad Sci. Cowan CM, Raymond LA. Selective neuronal degeneration in Huntington's disease.

Curr Top Dev Biol. Walker FO. Huntington's Disease. That cycle continues and makes more free radicals. Free radicals can damage the body's DNA. Our DNA contains our genes, proteins, lipids, cell membranes, and other important substances.

Damaged DNA can lead to disease. There are several theories about why our bodies age and free radicals are a key player in many of them. Free radicals are not considered fully responsible for aging-related changes, though; it's more likely that normal aging is related to many processes in the body.

Damage to genes in the DNA can cause them to make ineffective proteins. Some of those proteins are an important part of making sure the DNA is working right. A key area where damage can cause problems is in tumor suppressor genes. These genes direct the proteins that repair damaged DNA or cause cells that are damaged so badly they can't be fixed to be removed through "programmed cell death" apoptosis.

Usually, it's a series of mutations in tumor suppressor genes and other genes that lead a cancer cell to form. Many of the plant chemicals phytochemicals in our foods are antioxidants.

These nutrients stop the formation of free radicals and may reduce the damage they would cause in the body. The power of antioxidants to fight free radicals is one reason why a diet rich in vegetables and fruits has been linked with a lower risk of many diseases.

Examples of antioxidants that may help combat free radicals and oxidative stress include:. Many foods and drinks are good sources of different antioxidants , like berries and green tea.

Studies have shown that a diet rich in antioxidants is associated with a lower risk of many chronic diseases, including cancer.

However, using antioxidant supplements does not appear to have the same effect. For example, research had shown that people who had a higher intake of foods rich in beta-carotene and vitamin E had a lower risk of developing lung cancer. To find out why this might be the case, researchers did a study where one group of people took a daily supplement of beta-carotene, and the other did not to see if their risk of lung cancer would be affected.

The results were a bit surprising: the men in the study who smoked and took beta-carotene had a higher risk of developing lung cancer, not a lower risk. If you're having treatment for cancer, you might be worried about free radicals and wonder if you should up your antioxidant intake to fight off more damage.

Always talk to your oncologist about any supplement you're thinking about trying. They will guide you on what is safe to take or not while you are having treatment.

However, taking antioxidant supplements may worsen the prognosis for some cancers, and certain vitamin supplements may make cancer treatments less effective. In one study, postmenopausal women with breast cancer who used antioxidant supplements during chemotherapy and radiation had a poorer prognosis.

Two other, separate studies found that antioxidant supplements such as vitamin E may promote the growth and spread of lung cancer. While antioxidant supplements are often not recommended, your oncologist will likely encourage you to eat a balanced, nutritious diet that naturally contains antioxidants.

You can't completely avoid free radicals because they're part of a natural process in your body that you don't control.

You also can't always avoid being exposed to toxins—for example, you might run into them at your job. That said, you can do your best to avoid exposures and consider safety when you can't avoid them. You can also arm your body with antioxidants to fight free radicals.

While your body does make antioxidants, it doesn't make enough. For example, eating a "rainbow of foods" that will supply you with them is key. That said, even when people "do everything right"—like avoiding carcinogens and eating an antioxidant-rich diet—they can still get cancer or other diseases.

Free radicals are unstable molecules in the body that can damage DNA in cells. In turn, this can increase your risk for disease, including cancer.

The body naturally makes some free radicals as a byproduct of the processes it normally does, but you can also get more free radicals by exposure to certain toxic substances.

Antioxidants, like those found naturally in fruits and vegetables, are a key way to "fight" free radicals and the oxidative stress they cause in your body. However, antioxidant supplements are less likely to help and may even do more harm than good.

Phaniendra A, Jestadi DB, Periyasamy L. Free radicals: properties, sources, targets, and their implication in various diseases.

Indian J Clin Biochem.

Coping strategies for anxiety stress is an imbalance between free radicals raadicals antioxidants in Roole Role of free radicals. This can cause damage Role of free radicals organs and Roel and result in various radivals. You can help your body maintain balance by living a healthy lifestyle. Free radicals are oxygen-containing molecules with an uneven number of electrons. This uneven number of electrons allows free radicals to react easily with other molecules. Free radicals can cause large chain chemical reactions in your body because they react so easily with other molecules. These reactions are called oxidation. Role of free radicals

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