Antioxidants free radical pdf

Learn More. In recent years, there has been a great deal of attention toward the field of free radical chemistry. Free radicals reactive oxygen species and reactive nitrogen species are generated by our body by various endogenous systems, exposure to different physiochemical conditions or pathological states. A balance between free radicals and antioxidants is necessary for proper physiological function. If free radicals overwhelm the body's ability to regulate them, a condition known as oxidative stress ensues.

Free radicals thus adversely alter lipids, proteins, and DNA and trigger a number of human diseases. Hence application of external source of antioxidants can assist in coping this oxidative stress. Synthetic antioxidants such as butylated hydroxytoluene and butylated hydroxyanisole have recently been reported to be dangerous for human health.

Thus, the search for effective, nontoxic natural compounds with antioxidative activity has been intensified in recent years. The present review provides a brief overview on oxidative stress mediated cellular damages and role of dietary antioxidants as functional foods in the management of human diseases.

The recent growth in the knowledge of free radicals and reactive oxygen species ROS in biology is producing a medical revolution that promises a new age of health and disease management. Free radicals and antioxidants have become commonly used terms in modern discussions of disease mechanisms.

A free radical can be defined as any molecular species capable of independent existence that contains an unpaired electron in an atomic orbital.

The presence of an unpaired electron results in certain common properties that are shared by most radicals. Many radicals are unstable and highly reactive. They can either donate an electron to or accept an electron from other molecules, therefore behaving as oxidants or reductants. These are highly reactive species, capable in the nucleus, and in the membranes of cells of damaging biologically relevant molecules such as DNA, proteins, carbohydrates, and lipids.

Targets of free radicals include all kinds of molecules in the body. Among them, lipids, nucleic acids, and proteins are the major targets. Free radicals and other ROS are derived either from normal essential metabolic processes in the human body or from external sources such as exposure to X-rays, ozone, cigarette smoking, air pollutants, and industrial chemicals. Enzymatic reactions, which serve as source of free radicals, include those involved in the respiratory chain, in phagocytosis, in prostaglandin synthesis, and in the cytochrome P system.

Some internally generated sources of free radicals are[ 8 ]. Free radical reactions are expected to produce progressive adverse changes that accumulate with age throughout the body [ Table 1 ]. However, superimposed on this common pattern are patterns influenced by genetics and environmental differences that modulate free radical damage.

These are manifested as diseases at certain ages determined by genetic and environmental factors. Cancer initiation and promotion is associated with chromosomal defects and oncogene activation.

It is possible that endogenous free radical reactions, like those initiated by ionizing radiation, may result in tumor formation. The highly significant correlation between consumption of fats and oils and death rates from leukemia and malignant neoplasia of the breast, ovaries, and rectum among persons over 55 years may be a reflection of greater lipid peroxidation.

These compounds induce endothelial cell injury and produce changes in the arterial walls. Free radicals[ 11 — 13 ]. The term is used to describe the condition of oxidative damage resulting when the critical balance between free radical generation and antioxidant defenses is unfavorable. These injured tissues produce increased radical generating enzymes e.

The initiation, promotion, and progression of cancer, as well as the side-effects of radiation and chemotherapy, have been linked to the imbalance between ROS and the antioxidant defense system. ROS have been implicated in the induction and complications of diabetes mellitus, age-related eye disease, and neurodegenerative diseases such as Parkinson's disease. A role of oxidative stress has been postulated in many conditions, including anthersclerosis, inflammatory condition, certain cancers, and the process of aging.

Oxidative stress is now thought to make a significant contribution to all inflammatory diseases arthritis, vasculitis, glomerulonephritis, lupus erythematous, adult respiratory diseases syndrome , ischemic diseases heart diseases, stroke, intestinal ischema , hemochromatosis, acquired immunodeficiency syndrome, emphysema, organ transplantation, gastric ulcers, hypertension and preeclampsia, neurological disorder Alzheimer's disease, Parkinson's disease, muscular dystrophy , alcoholism, smoking-related diseases, and many others.

Heart diseases continue to be the biggest killer, responsible for about half of all the deaths. The oxidative events may affect cardiovascular diseases therefore; it has potential to provide enormous benefits to the health and lifespan. Poly unsaturated fatty acids occur as a major part of the low density lipoproteins LDL in blood and oxidation of these lipid components in LDL play a vital role in atherosclerosis.

Oxidized LDL is antherogenic and is thought to be important in the formation of anthersclerosis plaques. Furthermore, oxidized LDL is cytotoxic and can directly damage endothelial cells. Antioxidants like B-carotene or vitamin E play a vital role in the prevention of various cardiovascular diseases. Reactive oxygen and nitrogen species, such as super oxide anion, hydrogen peroxide, hydroxyl radical, and nitric oxide and their biological metabolites also play an important role in carcinogenesis.

Numerous investigators have proposed participation of free radicals in carcinogenesis, mutation, and transformation; it is clear that their presence in biosystem could lead to mutation, transformation, and ultimately cancer. Induction of mutagenesis, the best known of the biological effect of radiation, occurs mainly through damage of DNA by the HO.

Radical and other species are produced by the radiolysis, and also by direct radiation effect on DNA, the reaction effects on DNA. The reaction of HO. Radicals is mainly addition to double bond of pyrimidine bases and abstraction of hydrogen from the sugar moiety resulting in chain reaction of DNA. These effects cause cell mutagenesis and carcinogenesis lipid peroxides are also responsible for the activation of carcinogens.

B-carotene may be protective against cancer through its antioxidant function, because oxidative products can cause genetic damage. Thus, the photo protective properties of B-carotene may protect against ultraviolet light induced carcinogenesis. Immunoenhancement of B-carotene may contribute to cancer protection.

B-carotene may also have anticarcinogenic effect by altering the liver metabolism effects of carcinogens. Vitamin E, an important antioxidant, plays a role in immunocompetence by increasing humoral antibody protection, resistance to bacterial infections, cell-mediated immunity, the T-lymphocytes tumor necrosis factor production, inhibition of mutagen formation, repair of membranes in DNA, and blocking micro cell line formation.

The administration of a mixture of the above three antioxidant reveled the highest reduction in risk of developing cardiac cancer. The human body is in constant battle to keep from aging. Research suggests that free radical damage to cells leads to the pathological changes associated with aging.

Some of the nutritional antioxidants will retard the aging process and prevent disease. Based on these studies, it appears that increased oxidative stress commonly occurs during the aging process, and antioxidant status may significantly influence the effects of oxidative damage associated with advancing age. Research suggests that free radicals have a significant influence on aging, that free radical damage can be controlled with adequate antioxidant defense, and that optimal intake of antioxidant nutrient may contribute to enhanced quality of life.

Recent research indicates that antioxidant may even positively influence life span. Proteins can be oxidatively modified in three ways: oxidative modification of specific amino acid, free radical mediated peptide cleavage, and formation of protein cross-linkage due to reaction with lipid peroxidation products.

Protein containing amino acids such as methionine, cystein, arginine, and histidine seem to be the most vulnerable to oxidation. Oxidative damage to protein products may affect the activity of enzymes, receptors, and membrane transport. Oxidatively damaged protein products may contain very reactive groups that may contribute to damage to membrane and many cellular functions. Peroxyl radical is usually considered to be free radical species for the oxidation of proteins.

ROS can damage proteins and produce carbonyls and other amino acids modification including formation of methionine sulfoxide and protein carbonyls and other amino acids modification including formation of methionine sulfoxide and protein peroxide.

Protein oxidation affects the alteration of signal transduction mechanism, enzyme activity, heat stability, and proteolysis susceptibility, which leads to aging.

Oxidative stress and oxidative modification of biomolecules are involved in a number of physiological and pathophysiological processes such as aging, artheroscleosis, inflammation and carcinogenesis, and drug toxicity.

Lipid peroxidation is a free radical process involving a source of secondary free radical, which further can act as second messenger or can directly react with other biomolecule, enhancing biochemical lesions. Lipid peroxidation occurs on polysaturated fatty acid located on the cell membranes and it further proceeds with radical chain reaction. Hydroxyl radical is thought to initiate ROS and remove hydrogen atom, thus producing lipid radical and further converted into diene conjugate.

Further, by addition of oxygen it forms peroxyl radical; this highly reactive radical attacks another fatty acid forming lipid hydroperoxide LOOH and a new radical. Thus lipid peroxidation is propagated. Due to lipid peroxidation, a number of compounds are formed, for example, alkanes, malanoaldehyde, and isoprotanes. These compounds are used as markers in lipid peroxidation assay and have been verified in many diseases such as neurogenerative diseases, ischemic reperfusion injury, and diabetes.

It has been reported that especially in aging and cancer, DNA is considered as a major target. It has been reported that mitochondrial DNA are more susceptible to oxidative damage that have role in many diseases including cancer.

It has been suggested that 8-hydroxydeoxyguanosine can be used as biological marker for oxidative stress. An antioxidant is a molecule stable enough to donate an electron to a rampaging free radical and neutralize it, thus reducing its capacity to damage. These antioxidants delay or inhibit cellular damage mainly through their free radical scavenging property.

Some of such antioxidants, including glutathione, ubiquinol, and uric acid, are produced during normal metabolism in the body. The term antioxidant originally was used to refer specifically to a chemical that prevented the consumption of oxygen. In the late 19th and early 20th century, extensive study was devoted to the uses of antioxidants in important industrial processes, such as the prevention of metal corrosion, the vulcanization of rubber, and the polymerization of fuels in the fouling of internal combustion engines.

Early research on the role of antioxidants in biology focused on their use in preventing the oxidation of unsaturated fats, which is the cause of rancidity. However, it was the identification of vitamins A, C, and E as antioxidants that revolutionized the field and led to the realization of the importance of antioxidants in the biochemistry of living organisms.

Antioxidants act as radical scavenger, hydrogen donor, electron donor, peroxide decomposer, singlet oxygen quencher, enzyme inhibitor, synergist, and metal-chelating agents.

Both enzymatic and nonenzymatic antioxidants exist in the intracellular and extracellular environment to detoxify ROS. Two principle mechanisms of action have been proposed for antioxidants. Antioxidants may exert their effect on biological systems by different mechanisms including electron donation, metal ion chelation, co-antioxidants, or by gene expression regulation.

The antioxidants acting in the defense systems act at different levels such as preventive, radical scavenging, repair and de novo, and the fourth line of defense, i. The first line of defense is the preventive antioxidants, which suppress the formation of free radicals.

Although the precise mechanism and site of radical formation in vivo are not well elucidated yet, the metal-induced decompositions of hydroperoxides and hydrogen peroxide must be one of the important sources. To suppress such reactions, some antioxidants reduce hydroperoxides and hydrogen peroxide beforehand to alcohols and water, respectively, without generation of free radicals and some proteins sequester metal ions.

Glutathione peroxidase, glutathione-s-transferase, phospholipid hydroperoxide glutathione peroxidase PHGPX , and peroxidase are known to decompose lipid hydroperoxides to corresponding alcohols.

PHGPX is unique in that it can reduce hydroperoxides of phospholipids integrated into biomembranes. Glutathione peroxidase and catalase reduce hydrogen peroxide to water. Various endogenous radical-scavenging antioxidants are known: some are hydrophilic and others are lipophilic. Vitamin C, uric acid, bilirubin, albumin, and thiols are hydrophilic, radical-scavenging antioxidants, while vitamin E and ubiquinol are lipophilic radical-scavenging antioxidants.

Vitamin E is accepted as the most potent radical-scavenging lipophilic antioxidant. The third line of defense is the repair and de novo antioxidants. The proteolytic enzymes, proteinases, proteases, and peptidases, present in the cytosol and in the mitochondria of mammalian cells, recognize, degrade, and remove oxidatively modified proteins and prevent the accumulation of oxidized proteins.

The DNA repair systems also play an important role in the total defense system against oxidative damage. Various kinds of enzymes such as glycosylases and nucleases, which repair the damaged DNA, are known.

There is another important function called adaptation where the signal for the production and reactions of free radicals induces formation and transport of the appropriate antioxidant to the right site. Cells are protected against oxidative stress by an interacting network of antioxidant enzymes. This detoxification pathway is the result of multiple enzymes, with superoxide dismutases catalyzing the first step and then catalases and various peroxidases removing hydrogen peroxide. Superoxide dismutases SODs are a class of closely related enzymes that catalyze the breakdown of the superoxide anion into oxygen and hydrogen peroxide.

Mn-SOD is present in mitochondria and peroxisomes. Fe-SOD has been found mainly in chloroplasts but has also been detected in peroxisomes, and CuZn-SOD has been localized in cytosol, chloroplasts, peroxisomes, and apoplast.

In humans as in all other mammals and most chordates , three forms of superoxide dismutase are present. The first is a dimer consists of two units , while the others are tetramers four subunits. Catalase is a common enzyme found in nearly all living organisms, which are exposed to oxygen, where it functions to catalyze the decomposition of hydrogen peroxide to water and oxygen.

To this end, catalase is frequently used by cells to rapidly catalyze the decomposition of hydrogen peroxide into less reactive gaseous oxygen and water molecules. The glutathione system includes glutathione, glutathione reductase, glutathione peroxidases, and glutathione S-transferases. This system is found in animals, plants, and microorganisms. There are at least four different glutathione peroxidase isozymes in animals. The glutathione S-transferases show high activity with lipid peroxides.

These enzymes are at particularly high levels in the liver and also serve in detoxification metabolism. As it cannot be synthesized in humans and must be obtained from the diet, it is a vitamin. In cells, it is maintained in its reduced form by reaction with glutathione, which can be catalyzed by protein disulfide isomerase and glutaredoxins. Glutathione is a cysteine-containing peptide found in mostforms of aerobic life.

Glutathione has antioxidant properties since the thiol group in its cysteine moiety is a reducing agent and can be reversibly oxidized and reduced. In cells, glutathione is maintained in the reduced form by the enzyme glutathione reductase and in turn reduces other metabolites and enzyme systems as well as reacting directly with oxidants.

Melatonin, also known chemically as N-acetylmethoxytryptamine,[ 65 ] is a naturally occurring hormone found in animals and in some other living organisms, including algae. Hydroxyl radicals are short lived species with a These superoxide radicals are considered primary half life of unlike superoxide radicals that are ROS and can produce secondary ROS through relatively stable; hence react with molecules at interaction with other molecules directly or close proximity with high affinity Droge, Depending on the environment and PH.

Under conditions low PH. However, hydroperoxyl is physiologically with H2O2 in the Fenton reaction to form important because of its ability to penetrate hydroxyl radicals Lobo et al. More Reactive nitrogen species RNS are nitrogen- significantly, superoxide radicals has the ability to containing free radicals which possess high undergo dismutation where one superoxide oxidizing ability hence involved in promoting radical react with another superoxide radical oxidative stress Aruoma, They are most leading to formation of oxygen and hydrogen times classified as part of reactive oxygen species peroxide Valko et al.

NO-2 together with This is a product of dismutation reaction of non-radicals such as peroxynitrite ONOO- superoxide radicals Droge, Under besides others Blaise et al. Below is a physiological conditions, peroxisomes are the brief insight into nitric oxide and peroxynitrite.

In NO was acclaimed enzyme. Its product cGMP modulates the function "molecule of the year" in science magazine of protein kinases, ion channels and other because of its extraordinary properties Habib and physiologically important targets, the most Ali, It is soluble in aqueous and lipid relevant ones being regulation of smooth muscle media, a property that enables it to readily diffuse tone and inhibition of platelet adhesion.

It has a half-life of only a few During inflammatory process, cells of the immune seconds in aqueous environment and a greater system produce both nitric oxide and superoxide stability in environment with lower oxygen through oxidative burst Victor et al.

Under these conditions, nitric oxide and In extracellular milieu NO reacts with oxygen and superoxide anion may react together to produce water to form nitrate and nitrite anions. However NO toxicity is predominantly linked to its ability many tissues express one or more of these to combine to superoxide anions May and Qu, isoforms. Just like free radicals, antioxidants can be endogenously produced e.

The regulation of Amber et al. Antioxidants primarily vascular tone by cGMP is unique. The enzyme function to balance out free radicals generated soluble guanylate cyclase sGC is known to be during metabolic processes including during activated by both hydrogen peroxide and NO mechanisms involved in protecting the gut from Victor et al. Endogenous The Glutathione system comprises of four main antioxidants can further be classified into classes; Glutathione reductase, Glutathione enzymatic or non-enzymatic.

Enzymatic peroxidise GPx competes with catalase for H2O2 antioxidants are superoxide dismutase SOD , and is the major source of protection against low catalase and the glutathione system Rahman, levels of oxidative stress and Glutathione S- ;Ofor et al.

Mn-SOD has been found acids in cells. It is a cysteine containing peptide. In cells it is maintained as Glutathione al. Furthermore, three forms of SOD are reductase which subsequently reduces other said to be present; SOD1 in the cytoplasm , metabolites and enzyme systems while still SOD2 in the mitochondria and SOD3 capable of reacting with oxidants.

It plays a extracellular , with SOD1 and SOD3 containing pivotal role in maintaining cells redox state hence copper and zinc as their reactive centre and SOD2 recognized as one of the most important cellular containing manganese as its reactive centre antioxidant Rahman, Victor et al.

Unlike other antioxidants melatonin does not undergo redox recycling repeated reduction Catalase and oxidation ,once oxidized cannot be reduced to previous state because it forms several stable end This is predominant in cells exposed to oxygen products when it reacts with free radicals. Thus and is frequently used to catalyse the has been termed terminal or suicidal antioxidant decomposition of H2O2 by product of a range of Gutteridge, ; Rahman, normal metabolic processes to oxygen and water Schwentker et al.

Catalase has one of the Ascorbic acid Vitamin C highest turnover rates for all enzymes; with one molecule of catalase being able to convert Vitamin C is usually maintained in the reduced approximately 6million molecules of H2O2 to form in the body by its reaction with glutathione water and oxygen each minute.

It can be found in which can be catalysed by protein. Uric acid is thought to have substituted exogenous antioxidant intake have produced ascorbate in evolution Rahman, Just like mixed results. Randomised controlled clinical ascorbate, uric acid is capable of initiating trials believed to provide the most powerful and production of free radical species.

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