Rathod et al.

, J Forensic Toxicol Pharmacol 2014, 3:2

http://dx.doi.org/10.4172/2325-9841.1000119

Journal of Forensic
Toxicology & Pharmacology

Review Article

Hazards of Free Radicals in

Various Aspects of Health A
Review
Gunvanti B Rathod1*, Pragnesh Parmar2, Sangita Rathod3 and
Ashish Parikh4

Abstract
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 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, Alzheimers disease Parkinsons
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.

Keywords
Free radicals; Health hazards; Aging

Introduction
The 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

*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

International Publisher of Science,

Technology and Medicine

a SciTechnol journal
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 O2reacts 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 Hunds 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

All articles published in Journal of Forensic Toxicology & Pharmacology are the property of SciTechnol, and is protected by
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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.

doi:http://dx.doi.org/10.4172/2325-9841.1000119
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
Volume 3 Issue 2 1000119

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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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.

doi:http://dx.doi.org/10.4172/2325-9841.1000119
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 O2generation 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.
Volume 3 Issue 2 1000119

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 Parkinsons 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
(Alzheimers disease, Parkinsons 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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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.

doi:http://dx.doi.org/10.4172/2325-9841.1000119
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-2deoxyguanosine 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
Volume 3 Issue 2 1000119

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 radicalmediated 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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doi:http://dx.doi.org/10.4172/2325-9841.1000119
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

Volume 3 Issue 2 1000119

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.

Summary
Under 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, Alzheimers
disease Parkinsons 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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Author Affiliations

Top

Department of Pathology, SBKS Medical Institute and Research Centre,

Vadodara 391760, Gujarat, India
2
Department of Forensic Medicine, SBKS Medical Institute and Research
Centre Vadodara 391760, Gujarat, India
3
Department of Medicine, AMC MET Medical College, Sheth LG General
Hospital, Ahmedabad, Gujarat, India
4
Gayatri Hospital, Gandhinagar 382007, Gujarat, India
1

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