a S c i T e c h n o l j o u r n a lReview Article

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Hazards of Free Radicals in Various Aspects of Health – A ReviewGunvanti B Rathod1*, Pragnesh Parmar2, Sangita Rathod3 and Ashish Parikh4

AbstractThe 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 are intimately involved in the cellular damage - the common pathway for cancer, aging, and a variety of diseases. Formation of free radicals has been implicated as playing a role in the etiology of cardiovascular disease, cancer, Alzheimer’s disease Parkinson’s disease, and many more. The scientific community has begun to unveil some of the mysteries surrounding this topic, and the media has begun whetting our thirst for knowledge. So that it is a basic need to know about toxic effects of free radicals affecting general health of human body.

KeywordsFree radicals; Health hazards; Aging

*Corresponding author: Dr. Gunvanti B Rathod, Assistant Professor, Department of Pathology, SBKS Medical Institute and Research Centre, Vadodara-391760, Gujarat, India, Tel: 8141905206; E-mail: neempath@gmail.com

Received: March 05, 2014 Accepted: April 11, 2014 Published: April 17, 2014

and malignant neoplasias of the breast, ovaries, and rectum among persons over 55 years may be a reflection of greater lipid peroxidation [2]. Studies on atherosclerosis reveal the probability that the disease may be due to free radical reactions involving diet-derived lipids in the arterial wall and serum to yield peroxides and other substances. These compounds induce endothelial cell injury and produce changes in the arterial walls [3].

ROS sources and their sub cellular distribution

Free radicals and other ROS are derived either from normal essential metabolic processes in the human body or from external sources [4]. Total number of internally generated sources of free radicals are [5] Mitochondria, Xanthine oxidase, Peroxisomes, Inflammation, Phagocytosis, Arachidonate pathways, Exercise, Ischemia/reperfusion injury etc. Some externally generated sources of free radicals are Cigarette smoke, Environmental pollutants, Radiation, Certain drugs, pesticides, Industrial solvents, Ozone etc.

Intracellular sources of free radicals

Free radical formation occurs continuously in the cells as a consequence of both enzymatic and non-enzymatic reactions.

Enzymatic reactions

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-450 system [6].

In the respiratory chain

The electron transport chain (ETC), which is found in the inner mitochondrial membrane, utilizes oxygen to generate energy in the form of adenosine triphosphate (ATP). Incomplete reduction of O2 leads to the generation of superoxide anion (O2-), hydrogen peroxide (H2O2), and hydroxyl radical (OH). O2- is unstable with a lifetime of milliseconds at neutral pH, and in aqueous solution it spontaneously reacts or dismutates to yield H2O2 and O2. The OH is an extremely reactive and short-lived free radical produced in biological systems. In the Haber-Weiss reaction, O2 and two OH are formed when O2- reacts spontaneously with H2O2. In the Fenton reaction (also known as the iron-catalyzed Haber-Weiss reaction), reduction or oxidation of a trace metal in the presence O2- and H2O2 gives rise to OH. The chemical mechanisms of free radical reactions in biological systems have been previously described [7] and recently extensively reviewed [8]. Singlet oxygen is not a free radical, but can be formed during radical reactions and also cause further reactions. Singlet oxygen violates Hund’s rule of electron filling in that it has eight outer electrons existing in pairs leaving one orbital of the same energy level empty. When oxygen is energetically excited one of the electrons can jump to empty orbital creating unpaired electrons [9]. Singlet oxygen can then transfer the energy to a new molecule and act as a catalyst for free radical formation. The molecule can also interact with other molecules leading to the formation of a new free radical.

During exercise

Oxygen acts as the terminal electron acceptor within the ETC. The literature suggests that anywhere from 2 to 5% [10] of the total

IntroductionThe ability to utilize oxygen has provided humans with the benefit

of metabolizing fats, proteins, and carbohydrates for energy; however, it does not come without cost. Oxygen is a highly reactive atom that is capable of becoming part of potentially damaging molecules commonly called “free radicals.” The recent growth in the knowledge of free radicals and reactive oxygen species (ROS) in biology is producing a medical revolution. Free radical reactions are expected to produce progressive adverse changes that accumulate with age throughout the body. These are manifested as diseases at certain ages determined by genetic and environmental factors. The most important oxygen-containing free radicals in many disease states are hydroxyl radical, superoxide anion radical, hydrogen peroxide, oxygen singlet, hypochlorite, nitric oxide radical, and peroxynitrite radical. 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 [1].

In the recent era, cancer and atherosclerosis are two major causes of death. We can term them as salient “free radical” diseases. Tumor formation can occur by endogenous free radical reactions, like those initiated by ionizing radiation. The highly significant correlation between consumption of fats and oils and death rates from leukemia

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oxygen intake during both rest and exercise have the ability to form the highly damaging superoxide radical via electron escape. Oxygen consumption greatly increases during exercise, which leads to increased free radical production. During exercise oxygen consumption increases 10 to 20 fold to 35-70 ml/kg/min. In turn, electron escape from the ETC is further enhanced [11]. Electrons appear to escape from the ETS at the ubiqunone-cytochrome c level [10].

Free radical production by cytolytic cells

Certain leucocytes, in particular, the neutrophil [12,13] and the macrophage, [14] have a very potent system mobilizable to their cell surface which can generate as primary product the superoxide radical. As we have heard elsewhere in this meeting, the superoxide radical can be converted in biological systems to a variety of potentially more damaging radicals, for instance, the hydroxyl radical, peroxy and alkoxy radicals on lipids, etc. In addition, the superoxide radical is itself directly damaging in certain circumstances, for instance, in acting upon papain and some other enzymes [15]. The so called ‘oxidative burst’ responsible for the production of the superoxide radical by leucocytes has now been extensively characterized [12,13]. It involves the assembly on the cell surface of an electron transport chain and the resulting flux of superoxide radicals is directed to the exterior of the cell or in some circumstances to the interior of a newly formed phagosome enclosing a target cell. The mechanisms by which such radicals contributed to cytolysis of the target cells are not entirely clear, but it has been argued that collaboration between the primary radical products and transition metals generating the hydroxyl radicals is of some importance. At the same time collaboration with halides, generating molecules such as hypochlorous acid may be very important and may interact with available peroxidases present also in the phagocytic vacuole.

Most of the products mentioned so far are relatively unstable highly reactive molecules, but hypochlorous acid can interact with certain nitrogen containing compounds to give much more long-lived but very damaging chloramine species. There has been some debate as to whether a specialized cytolytic cell, the natural killer (NK) cell, also produces a triggered radical burst in response to presentation of appropriate target cells. In general, the evidence is now in favor of the view that NK cells are not capable of a radical burst and that previous observations to the contrary were due to contamination of the NK cell preparations by mononuclear phagocytes. However, Duwe et al. (1985) [16] have presented evidence that radical production is not due to a specialized surface oxidase system but rather that intracellular lipoxygenase pathways may contribute to NK mediated cytolysis and this matter is still open for further analysis. Intimate contact between the effector cell and its target is necessary for most well characterized mechanisms of cellmediated cytolysis and it seems that free radical production by leucocytes may often contribute to their cytolytic mechanism. Free radicals contribute to cytolysis by damging membrane transport systems of the plasma membrane of target cells.

During ischemia and reperfusion injury

In 1968, McCord and Fridovich proposed that the enzyme xanthine oxidase was the major source of free radicals that contributed to reperfusion injury [17]. Altered peripheral perfusion decreases the oxygen available to peripheral tissues that is required for adenosine triphosphate (ATP) production. As ATP depletion occurs, the level of adenosine monophosphate (AMP) raises that, in

turn, is catabolized to hypoxanthine. Aggressive volume resuscitation and the return of molecular oxygen to previously ischemic tissues result in hypoxanthineserving as a substrate for xanthine oxidase.

In a series of complicated reactions, hypoxanthineis converted to xanthine and ultimately to uric acid, and this process produces hydrogen peroxide and superoxide, deleterious oxygen-derived free radicals. This burst of superoxide and hydrogen peroxide overwhelms the scavaging capacity of endogenous enzymes. It is now clear that adherent and activated neutrophils produce a burst of free radicals [18-21]. This neutrophil related function serves a significant protective mechanism in normovolemia by scavaging invading bacteria; however, with injury a burst of neutrophil produced free radicals may exacerbate xanthine oxidase activity, producing overwhelming tissue damage.

After any trauma

There is increasing evidence that major trauma produces abundant free radicals and impairs endogenous free radical scavenging mechanisms. Free radicals may directly impair some aspect of cell membrane or intracellular organelle function or may initiate an inflammatory signaling cascade that results in the production of numerous mediators of cell injury. While considerable attention has focused on free radical generation during low flow states, ischemia, and subsequent volume resuscitation and reoxygenation, recent attention has focused on the role of activated neutrophil in cell mediated injury after trauma.

Intracellular adhesion molecules 1 and 2 (ICAM-1 and ICAM-2) have been shown to be up regulated by several types of shock [21-23]. These adhesion molecules are involved in the binding of leukocytes to the vascular endothelium; and as neutrophil adhere to the vascular endothelium, they subsequently migrate into tissue. Thus neutrophil derived free radicals play a significant role in tissue injury after trauma.

Vascular endothelial cells as a source

It has been shown that endothelial cells produce a factor, EDRF, which promotes vascular smooth muscle relaxation. [24,25] This factor was chemically identified as NO, a labile free radical [25-27]. Vascular endothelial cells contain an enzyme, nitric oxide synthase (NOS), which synthesizes NO [28]. To date, three major NOS isoforms have been identified. All 3 NOS isoforms (nNOS, eNOS, or iNOS) can become potent sources of O2- with depletion of either the substrate l-arginine or the co-factor BH4 triggering this fundamental alteration in NOS function. [29-31] NOS1 and NOS3 are constitutive, and calcium and calmodulin dependent. NOS1 primarily involved in neurons, and NOS3 primarily involved in endothelial cells. The third isoform, NOS2, is inducible and calcium independent and is primarily involved in inflammation. Each of the three NOS isoforms converts l-arginine to l-citrulline and NO, and require the substrates NADPH and oxygen as well as the co-factor tetrahydrobiopterin (BH4). Only small quantities of NO are produced for brief periods when intracellular Ca2+ levels are elevated. The process of vascular and myocardial NOS generation is greatly altered by ischemia [32]. NO has been shown to react with superoxide to form the highly reactive oxidant, peroxynitrite, ONOO−, which can cause tissue injury [33,34]. Based on this, it has been suggested that NO formation may be of critical importance in modulating the toxicity of superoxide or other oxidants [34]. Over the last several years, it has been suggested that alterations in NO formation in ischemic tissue result in post-

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ischemic injury. It was shown that vascular reactivity is decreased in the post-ischemic tissues [35-37] and inferred that this was due to altered NO production or breakdown; This was shown to be due to both NOS-dependent formation during the early period of ischemia, and increasingly due to the reduction of tissue nitrite with prolonged ischemia. In addition, it has been shown that under conditions of arginine or BH4 depletion, as induced by oxidant stress, NOS becomes uncoupled and switches from NO to superoxide generation [38-40]. Since BH4 can be readily depleted by oxidants, oxidation of BH4 could result in a switch of NOS from NO to O2- generation. There are also other mechanisms that could trigger uncontrolled O2- generation including release of FAD from the enzyme, disruption of the active dimer, structural changes resulting in uncoupling of the reductase and oxygenase sites [27].

Via lipid peroxidation

Polyunsaturated fatty acids (PUFAs) are abundant in cellular membranes and in low-density lipoproteins (LDL) .The PUFAs allow for fluidity of cellular membranes. A free radical prefers to steal electrons from the lipid membrane of a cell, initiating a free radical attack on the cell known as lipid peroxidation. It 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.. Reactive oxygen species target the carbon-carbon double bond of polyunsaturated fatty acids. The double bond on the carbon weakens the carbon-hydrogen bond allowing for easy dissociation of the hydrogen by a free radical. A free radical will steal the single electron from the hydrogen associated with the carbon at the double bond. In turn this leaves the carbon with an unpaired electron and hence becomes a free radical. In an effort to stabilize the carbon-centered free radical molecular rearrangement occurs. The newly arranged molecule is called a conjugated diene (CD). The CD then very easily reacts with oxygen to form a proxy radical. The proxy radical steals an electron from another lipid molecule in a process called propagation. This process then continues in a chain reaction [41]. 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 [42].

Free radicals can also be formed in non-enzymatic reactions of oxygen with organic compounds as well as those initiated by ionizing reactions.

Balance between free radicals and antioxidants

To protect the cells and organ systems of the body against reactive oxygen species, humans have evolved a highly sophisticated and complex antioxidant protection system. It involves a variety of components, both endogenous and exogenous in origin, that function interactively and synergistically to neutralize free radicals. These components include endogenous, dietary, ROS neutralizing antioxidants and metal binding proteins.

Endogenous antioxidants

Endogenous Antioxidants are Bilirubin, Thiols, e.g., glutathione, lipoic acid, N-acetyl cysteine, NADPH and NADH, Ubiquinone (coenzyme Q10), Uric acid, Enzymes like copper/zinc and manganese-dependent superoxide dismutase (SOD), iron-dependent catalase, selenium-dependent glutathione peroxidase etc.

Dietary antioxidants

Dietary Antioxidants are Vitamin C, Vitamin E, Beta carotene and other carotenoids and oxycarotenoids, e.g., lycopene and lutein and Polyphenols, e.g., flavonoids, flavones, flavonols, and proanthocyanidins.

Metal binding proteins

Metal Binding Proteins are Albumin (copper), Ceruloplasmin (copper), Metallothionein (copper), Ferritin (iron), Myoglobin (iron), Transferrin (iron) etc.

ROS neutralizing antioxidants

ROS neutralizing antioxidants are Hydroxyl radical vitamin C, glutathione, flavonoids, lipoic acid, Superoxide radical vitamin C, glutathione, flavonoids, SOD, Hydrogen peroxide vitamin C, glutathione, beta carotene, vitamin E, CoQ10, flavonoids, lipoic acid, Lipid peroxides beta carotene, vitamin E, ubiquinone, flavonoids, glutathione peroxidase [43].

Oxidative stress

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 [44]. An imbalance between free radical production and antioxidant defenses ultimately leads to formation of oxidative stress. This is associated with damage to a wide range of molecular species including lipids, proteins, and nucleic acids [45]. ROS have been implicated in the induction and complications of diabetes mellitus, age-related eye disease, and neurodegenerative diseases such as Parkinson’s disease [46].

Oxidative stress and human diseases

Oxidation of lipids and proteins leads to changes in structure and functions which is the end result of excess of oxidative stress. Oxidative damage to DNA, proteins, and other macromolecules has been implicated in the pathogenesis of a wide variety of diseases, most notably heart disease and cancer [43].

Oxidative stress is strongly associated with all inflammatory diseases (arthritis, vasculitis, glomerulonephritis, lupus erythematous, adult respiratory diseases syndrome), ischemic diseases (heart diseases, stroke, intestinal ischemia), 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 [47].

Oxidative damage to protein

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 [48]. It is now clear that the hydroxyl radical in particular is capable of both modifying amino acid residues within proteins and of fragmenting polypeptides [49]. Free radical mediated protein modification increases susceptibility to enzyme proteolysis. 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.

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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 damage to DNA

Many experiments clearly provide evidences that DNA and RNA are susceptible to oxidative damage. It has been reported that especially in aging and cancer, DNA is considered as a major target [50]. Oxidative nucleotide as glycol, dTG, and 8-hydroxy-2-deoxyguanosine is found to be increased during oxidative damage to DNA under UV radiation or free radical damage. 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-hydroxy-2-deoxyguanosine can be used as biological marker for oxidative stress [51].

Cell surface targets for free radicals

Damage to plasma membrane transport proteins (pumps, carriers and channels) are commonly the important mechanisms by which homeostasis of ions is perturbed [52]. Membrane potential is a reflection of ionic distributions across the cell membrane, probably mainly governed by pumping [53] and hence, when transport proteins and carriers are damaged during free radical attack, it is to be expected that membrane potential will not be maintained at its normal level. It is interesting that sodium channel operation involves radical intermediates; this implies that exogenous radicals might interfere with ion transport not only by damaging proteins, but also by interacting directly with transport intermediates [54]. Free radical flux is assembled by the combination of iron and H2O2; there is a rapid depolarization of the cells detectable within short period of exposure to the radical generating combination. Once depolarization has commenced under the attack of iron and H2O2, it cannot be stopped by adding iron chelators and catalase. On the other hand, if the iron chelator desferal and catalase are added prior the addition of iron and H2O2, all the subsequent events can be prevented. Lipid peroxidation might cause some slight changes in membrane capacitance, it does not seem likely that this would be sufficiently drastic to cause the catastrophic abnormalities in ion homeostasis which lead to osmotic lysis. On the other hand, damage to even a relatively small proportion of pumping and carrier proteins might have an exaggerated effect on ionic homeostasis; the effect being exaggerated by virtue of the catalytic nature of the molecules being damaged, the transport proteins.

Lipid peroxidation

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 neurodegenerative diseases, ischemic reperfusion injury, and diabetes [55].

Cardiovascular diseases

Heart disease is the leading cause of death, 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.

Damage to the myocardium by free radicals

Free radical-mediated processes can play a significant role in the production of irreversible cellular injury, a finding of particular relevance in view of the hypothesized role for free radical injury during reoxygenation [56]. According to this hypothesis, normal cardiac tissue contains enzymatic chemical agents capable of detoxifying highly reactive free radical compounds derived mainly from molecular oxygen. Recent work has suggested a role for free radical mediated processes in myocardial damage, especially with respect to the reoxygenation of hypoxic tissue [57-60].

During ischemia, several conditions prevail which lead to increased free radical formation upon reintroduction of oxygen. These include the intracellular accumulation of reducing equivalents, the conversion of xanthine dehydrogenase to xanthine oxidase, and the accumulation of by-products of ATP hydrolysis which act as substrates for free radical production through the action of xanthine oxidase [61,62]. The subsequent reintroduction of oxygen during reperfusion leads to increased reduction of molecular oxygen and increased free radical levels. The cell, unable to detoxify this radical load, suffers irreversible injury, largely related to the peroxidation of membrane lipids. It has been suggested that an exogenous supply of radical scavenging agents prior to and during reperfusion of ischemic tissue can minimize this type of radical-mediated injury.

Irreversible injury has been shown to be closely correlated with the loss of membrane integrity [63] and since oxygen radical-mediated injury is primarily directed at unsaturated lipid constituents of the cell membrane [56,61]. Certain antioxidant compounds (e.g., selenium and tocopherols) are capable of decreasing this reoxygenation damage, presumably by a mechanism involving free radical detoxification or “scavenging’ [57,60].

Role of free radicals in atherosclerosis

Several factors are associated with production of atherosclerosis, such as high cholesterol levels, hypertension, cigarette smoking, and diabetes. A growing body of evidence suggests a critical step in its development is the oxidation of low-density lipoprotein (LDL) within the arterial wall [64].

The three most important cell types in the vessel wall are endothelial cells; smooth muscle cell and macrophage can release free radical, which affect lipid peroxidation [65]. With continued high level of oxidized lipids, blood vessel damage to the reaction process continues and can lead to generation of foam cells and plaque the

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symptoms of atherosclerosis. Oxidized LDL is responsible for the formation of atherosclerosis plaques. Furthermore, oxidized LDL is cytotoxic and can directly damage endothelial cells.

Role of free radicals in carcinogenesis

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. Both cigarette smoking and chronic inflammation, two of the major causes of cancer have strong free radical components in their mechanisms of action.

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. 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.

Pulmonary disorders

Because of its large surface area, the respiratory tract is a major target for free radical insult, not to mention the fact that air pollution is a major source of ROS [66,67]. Recent studies suggest that free radicals may be involved in the development of pulmonary disorders such as asthma [28]. Cellular damage caused by free radicals is thought to be partly responsible for the bronchial inflammation characteristic of this disease.

Other major pathologies that may involve free radicals include neurological disorders and cataracts [66]. Neural tissue may be particularly susceptible to oxidative damage because it receives a disproportionately large percentage of oxygen and it has a high concentration of polyunsaturated fatty acids which are highly prone to oxidation [69]. Formation of cataracts is believed to involve damage to lens protein by free radicals, causing the lens to lose its transparency.

Free radical and aging

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 [70]. Aging is characterized by decrements in maximum function and accumulation of mitochondrial DNA mutations, which are best observed in organs such as the brain that contain post-mitotic cells. Oxygen radicals are increasingly considered responsible for part of these aging changes. An increasing number of diseases or disorders, as well as aging process itself, demonstrate link either directly or indirectly to these reactive and potentially destructive molecules [71]. The major mechanism of aging attributes to DNA or the accumulation of cellular and functional damage [72]. Reduction of free radicals or decreasing their rate of production may delay aging. Some of the nutritional antioxidants will

retard the aging process and prevent disease. We can conclude that as the age advancing the oxidative stress increases. 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.

SummaryUnder normal conditions the antioxidant defense system within

the body can easily handle free radicals that are produced. Here we have concluded that during times of increased oxygen flux, free radical production may exceed that of removal, ultimately resulting in lipid peroxidation and damage to the tissues. Thus damage to cells caused by free radicals is believed to play a central role in the aging process and in the etiology of cardiovascular disease, cancer, Alzheimer’s disease Parkinson’s disease, and many more. Further work should lead to a greater understanding of the critical metabolic complexities in the biochemical transformations of molecular oxygen.

Acknowledgement

Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors/editors/publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.

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Citation: Rathod GB, Parmar P, Rathod S, Parikh A (2014) Hazards of Free Radicals in Various Aspects of Health – A Review. J Forensic Toxicol Pharmacol 3:2.

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Author Affiliations Top1Department of Pathology, SBKS Medical Institute and Research Centre, Vadodara – 391760, Gujarat, India2Department of Forensic Medicine, SBKS Medical Institute and Research Centre Vadodara – 391760, Gujarat, India3Department of Medicine, AMC MET Medical College, Sheth LG General Hospital, Ahmedabad, Gujarat, India4Gayatri Hospital, Gandhinagar – 382007, Gujarat, India