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ABSTRACT In recent years, there has been a large quantity of attention toward the field of free radical chemistry. Free radicals react (ROS) and reactive nitrogen species(RNS) are generated by our body by different endogenous systems, exposure to conditions or pathological states. A balance between free radicals and antioxidants is needful for proper physiological actio overwhelm the body's ability to regulate them, a condition known as oxidative stress ens proteins, and DNA and trigger a number of human diseases. Hence application of external source of antioxidants can assist in oxidative stress. Thus, the search for effective, nontoxic nat attendant review provides a brief overview on oxidative stress mediated cellular damages and role of dietary antioxidants as the management of human diseases.
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REVIEW ARTICLE
FREE RADICALS AND HUMAN HEALTH
1, *Mustafa Taha Mohammed, 2
Sura Mohammed Kadhim,
Jassimand and 1
Sarah Isam Abbas
1Department of
Chemistry, College of Science,
2Ministry of Education, Rusafa-1,
Baghdad, Iraq
Accepted
24
ABSTRACT
In recent years, there has been a large quantity of attention toward the field of free radical chemistry. Free radicals react
(ROS) and reactive nitrogen species(RNS) are generated by our body by different endogenous systems, exposure to
conditions or pathological states. A balance between free radicals and antioxidants is needful for proper physiological actio
overwhelm the body's ability to regulate them, a condition known as oxidative stress ens
proteins, and DNA and trigger a number of human diseases. Hence application of external source of antioxidants can assist in
oxidative stress. Thus, the search for effective, nontoxic nat
attendant review provides a brief overview on oxidative stress mediated cellular damages and role of dietary antioxidants as
the management of human diseases.
Key Words:
Free radicals, Oxidative stress, Antioxidant.
1- INTRODUCTION
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.
Man
y 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
(Cheeseman, 1993).
The most important oxygen
free radicals in many diseas
e 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
(Young and Woodside, 2001).
Free radicals attack important
macromolecules leading to cell damage and homeostatic
disruption. Targets of free radicals include all kinds of
mole
cules in the body. Among them, lipids, nucleic acids, and
proteins are the major targets.
2- Reactive Oxygen Species
Reactive oxygen species (ROS) is a term that encompasses all
highly reactive, oxygencontaining
molecules, including free
radicals. Types of ROS include the hydroxyl radical,the
superoxide anion radical, hydrogen peroxide, singlet oxygen,
nitric oxide radical,hypochlorite radical, and various lipid
peroxides. All are capable of reacting withmembrane
nucleic acids, proteins and enzymes, and other small
*Corresponding author:
Mustafa Taha Mohammed
Department of Chemistry, College of Science, Al
University, Baghdad, Iraq.
International Journal of
Innovation Sciences and
Vol.4, No.6, pp.218-223, June- 2015
FREE RADICALS AND HUMAN HEALTH
Sura Mohammed Kadhim,
1
Abdulkadir Mohammed Noori
Sarah Isam Abbas
Chemistry, College of Science,
Al-Mustansiriyah University,
Baghdad, Iraq
Baghdad, Iraq
24
th May, 2015; Published Online 30th June, 2015
In recent years, there has been a large quantity of attention toward the field of free radical chemistry. Free radicals react
(ROS) and reactive nitrogen species(RNS) are generated by our body by different endogenous systems, exposure to
conditions or pathological states. A balance between free radicals and antioxidants is needful for proper physiological actio
overwhelm the body's ability to regulate them, a condition known as oxidative stress ensues. Free radicals consequently adversely change lipids,
proteins, and DNA and trigger a number of human diseases. Hence application of external source of antioxidants can assist in
oxidative stress. Thus, the search for effective, nontoxic natural compounds with antioxidative activity has been intensified in recent years. The
attendant review provides a brief overview on oxidative stress mediated cellular damages and role of dietary antioxidants as
Free radicals, Oxidative stress, Antioxidant.
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.
y 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
The most important oxygen
-containing
e 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
biologically relevant
molecules such as DNA, proteins, carbohydrates, and lipids
Free radicals attack important
macromolecules leading to cell damage and homeostatic
disruption. Targets of free radicals include all kinds of
cules in the body. Among them, lipids, nucleic acids, and
Reactive oxygen species (ROS) is a term that encompasses all
molecules, including free
radicals. Types of ROS include the hydroxyl radical,the
superoxide anion radical, hydrogen peroxide, singlet oxygen,
nitric oxide radical,hypochlorite radical, and various lipid
peroxides. All are capable of reacting withmembrane
lipids,
nucleic acids, proteins and enzymes, and other small
Mustafa Taha Mohammed
Department of Chemistry, College of Science, Al
-Mustansiriyah
molecules, resultingin
cellular damage. ROS are generated by
a number of pathways. Most of the oxidantsproduced by cells
occur as:
A consequence of normal aerobic metabolism:
approximately 90% of the oxygenutilized
consumed by the mitochondrial electron transport system.
Oxidative burst from phagocytes (white blood cells) as
part of the mechanism by whichbacteria and viruses are
killed, and by which foreign proteins (antigens) are
denatured.
Xenobio
ticmetabolism, i.e., detoxification of toxic
substances.
Figure 1. An overall picture of the metabolism of ROS and the
mechanism of oxidative tissue damage leading to pathological
conditions
Innovation Sciences and
Research
Abdulkadir Mohammed Noori
Baghdad, Iraq
In recent years, there has been a large quantity of attention toward the field of free radical chemistry. Free radicals react
ive oxygen species
(ROS) and reactive nitrogen species(RNS) are generated by our body by different endogenous systems, exposure to
various physiochemical
conditions or pathological states. A balance between free radicals and antioxidants is needful for proper physiological actio
n. If free radicals
ues. Free radicals consequently adversely change lipids,
proteins, and DNA and trigger a number of human diseases. Hence application of external source of antioxidants can assist in
coping this
ural compounds with antioxidative activity has been intensified in recent years. The
attendant review provides a brief overview on oxidative stress mediated cellular damages and role of dietary antioxidants as
functional foods in
cellular damage. ROS are generated by
a number of pathways. Most of the oxidantsproduced by cells
A consequence of normal aerobic metabolism:
approximately 90% of the oxygenutilized
by the cell is
consumed by the mitochondrial electron transport system.
Oxidative burst from phagocytes (white blood cells) as
part of the mechanism by whichbacteria and viruses are
killed, and by which foreign proteins (antigens) are
ticmetabolism, i.e., detoxification of toxic
Figure 1. An overall picture of the metabolism of ROS and the
mechanism of oxidative tissue damage leading to pathological
conditions
Available online at
http://www.ijisr.com
Consequently, things like vigorous exercise, which accelerates
cellular metabolism; chronicinflammation, infections, and
there illnesses; exposure to allergens and the presence
ofsyndrome; and exposure to drugs or toxins such as cigarette
smoke, pollution,pesticides, and insecticides may all
contribute to an increase in the body’s oxidant load (Uday
Bandyopudyaet al., 1999; Chitra and Pillai, 2002)
3- Sources of reactive oxygen species and free radicals in
an organism
All aerobic organisms produce ROS physiologically. The five
most productive pathways are involved in regulating the
production of ROS/RNS and the resulting effects on signalling
cascades. The five mechanisms described produce ROS in a
nonregulated mode. However, there are many sources within
the cells that are only mentioned.
3.1. Regulated production of reactive oxygen and nitrogen
species
3.1.1. Nitric oxide synthase (NOS)
Nitric oxide (NO) is produced from a guanidine nitrogen of
Larginine via electron transfer from NADPH in two
successive steps.The enzyme responsible this exists in three
isoforms:neuronal (nNOS, type I, NOSI or NOS1),
endothelial (eNOS, type III, NOSIII or NOS3) and inducible
(iNOS, type II, NOSII or NOS2). nNOS and eNOS are
constitutively expressed, but their activity is regulated by the
intracellular Ca2+ concentration. nNOS exhibits
NADPHdiaphorase (NADPHd) activity (Miller, 2004).
3.1.2. NADPH oxidase
3.1.2.1. NADPH oxidase in phagocytic cells
Activated neutrophils and macrophages produce superoxide
and its derivatives as cytotoxic agents forming part of the
respiratory burst via the action of membrane bound NADPH
oxidase on molecular oxygen.
3.1.2.2. NADPH oxidase in nonphagocytic cells
Fibroblasts, endothelial cells, vascular smooth muscle cells,
cardiac monocytes and thyroid tissue nonphagocytic
NAD(P)H oxidase (similar but not identical to phagocytic
NADPH oxidase) produce O2
and to regulate intracellular
signalling cascades (Gieseet al., 2001; Zhaoet al., 2007). In
most of these, rac1 is involved in the induction of NAD(P)H
oxidase activity (Joneset al., 1996; Zweieret al., 1994).
Muscle cells and fibroblasts account for the majority of O2
produced in the normal vessel wall. The NAD(P)H oxidase
isoforms of the cardiovascular system are
membraneassociated enzyme that appear to utilize both
NADH and NADPH (Gieseet al., 2001).
3.1.3. Arachidonate cascade enzymes
3.1.3.1. lipoxygenase (5LOX)
The enzyme 5LOX has been identified as an inducible source
of ROS production inlymphocytes (Bonizziet al., 2000;
McIntyreet al., 1999), but the evidence for its physiological
role in redox signalling isstill scarce.
3.1.3.2. Cyclooxygenase (COX1)
Cyclooxygenase1 has been implicated in ROS production
through formation ofendoperoxides, which are susceptible to
scavenging by some antioxidants in cells stimulated with
TNFα, interleukin1, bacterial lipopolysaccharide, or the
tumor promoter 4Otetradecanoylphorbol13acetate (Dröge,
2002).
3.2. Nonregulated production of reactive oxygen species
3.2.1. Mitochondrial respiration
The fourelectron reduction of oxygen occurs within the
mitochondrial electron transport system of all cells
undergoing aerobic respiration. It is estimated that 23% of O2
consumed by mitochondria is incompletely reduced, yielding
ROS (Turrens, 2003) and 15% leads to H2O2production.It is
well documented that mitochondria are a source of H2O2;
however, the release of O2
from mitochondria into the
cytosol has yet to be definitively established (Molleret al.,
2007).
3.2.2. Chloroplasts
The ability of phototrophs to convert light into biological
energy is critical for life andtherefore organisms capable of
photosynthesis are especially at risk of oxidative damage,due
to their bioenergetic lifestyle and the abundance of
photosenzitizers and oxidablepolyunsaturated fatty acids in
the chloroplast envelope.
3.2.3. Xanthine oxidoreductase (XOR)
XOR exists as either an oxidase (XO) which transfers
reducing equivalents to oxygen, or as a dehydrogenase (XDH)
that utilizes NAD or oxygen as the final electron acceptor. The
enzyme is derived from xanthine dehydrogenase by
proteolytic cleavage. It contains molybdenum in the form of
molybdopterine, and two clusters with iron and sulfur
compounds of FAD cofactor in both subunits. The enzyme
catalyzes the production of uric acid with coproduction of
O2
. The physiological substrates, xanthine and hypoxanthine,
bind with the oxidized enzyme and donate two electrons into
the molybdenum cofactor reducing it from Mo6+ to Mo4+.
Substrates are hydroxylated by H2O at the molybdenum site as
the electrons travel via two ironsulfide residues to flavine–
adenine dinucleotide (FAD) (Hazellet al., 1994; Berry and
Hare, 2004).
3.2.4. Dopamine (DA)
As a neurotransmitter, DA is stable in the synaptic vesicle.
When an excess of cytosolic DA exists outside of the synaptic
vesicle, DA is easily metabolized via monoamino oxidase
(MAO) or by autooxidation to produce ROS, subsequently
leading to the formation of neuromelanin . During the
oxidation of DA by MAO, H2O2 and dihydroxyphenylacetic
acid are generated (Gill and Tuteja, 2010). Spontaneously
oxidized cytosolic DA produces O2
and reactive quinones
such as DA quinones or DOPA quinones. DA quinones are
also generated in the enzymatic oxidation of DA by COX in
the form of prostaglandin H synthase, LOX, tyrosinase and
XOR. These quinones are easily oxidized to the cyclized
aminochromes: Dachrome and DOPAchrome, and are then
finally polymerized to form melanin, as reviewed in
(Miyazaki and Asanuma, 2008). Although ROS from the
autooxidation of DA show widespread toxicity not only in DA
International Journal of Innovation Sciences and Research 219
ne
urons but also in other regions, highly reactive DA quinone
or DOPA quinone exert cytotoxicity predominantly in DA
neurons and surrounding neural cells. It is thought that DA
acts as an endogenous neurotoxin, contributing to the
pathology of neurodegenerat
ive disorders and
ischemia
induced damage in the striatum
Maragoset al., 2004).
3.2.5. Photosensitization reactions
Photosensitization reactions involve the oxidation of organic
compounds by atmosphericoxygen
upon exposure to visible
light. The photoexcitated state, most often the triplet stateof
the sensitizer, is the key photoreactive intermediate and exerts
photodamage throughdirect reaction with substrate molecules
(type I photosensitization) or activation
ofmolecular oxygen
by energy transfer reactions (type II photosensitization)
(Wondraket al., 2006). 1O2
is anexcited state molecule formed
by direct energy tranfer between the excited sensitizer
andground state 3O2
. Less than 1% of triplet oxygen is
converted in parallel to superoxide anion(O
of O2 as a precursor of H2O2
occurs via electron transfer via
productionof a sensitizer radical cation, or after an
intermediate reduction of the sensitizer
followed by the single electron reduction of O
2003; Croftset a., 2008).
3.3. Other cellular ROS sources
The most studied producers of O2
.
by oxidizing unsaturated
fatty acids and xenobiotics are cytochrome
family of enzymes (Thannickal and
Fanburg
leaking from nuclear membrane cytochrome oxidases and
electron transport systems may give rise to ROS. In addition
to intracellular membrane
associated oxidases, aldehyde
oxidase,
dihydroorotate dehydrogenase, flavoprotein
dehydrogenase and tryptofan dioxygenase can all generate
ROS during catalytic cycling. pH
dependent cell wall
peroxidases, germin
like oxalate oxidases and amine oxidases
have been proposed as a source of H2O2
plant cells (Bolwell andWoftastek, 1997)
. Glycolate oxidase,
D
amino acid oxidase, urate oxidase, flavin oxidase, L
hydroxy acid oxidase, and fatty acyl
important sources of total cellular H
2
peroxisomes (Foster and Stamler, 2004)
. Auto
small molecules such as epinephrine, flavins, and
hydroquinones can also be an important source of intracellular
ROS production (Foster and Stamler
, 2004)
4. Production route of free radicals
Production of
free radicals in the body is continuous and
inescapable. The basic causes include the following
(Lippincott Williams and
Wilkins Instructor’s Resource
2008):
4.1. The immune system
Immune system cells deliberately create oxy
ROS (Reactive
oxygen species) as weapons.
4.2. Energy production
During energy-
producing cell generates continuously and
abundantly oxy-
radicals and ROS as toxic waste. The cell
includes a number of metabolic processes, each of which can
International Journal of Innovation Sciences and
urons but also in other regions, highly reactive DA quinone
or DOPA quinone exert cytotoxicity predominantly in DA
neurons and surrounding neural cells. It is thought that DA
acts as an endogenous neurotoxin, contributing to the
ive disorders and
induced damage in the striatum
(Xiaet al., 2001;
Photosensitization reactions involve the oxidation of organic
upon exposure to visible
light. The photoexcitated state, most often the triplet stateof
the sensitizer, is the key photoreactive intermediate and exerts
photodamage throughdirect reaction with substrate molecules
ofmolecular oxygen
by energy transfer reactions (type II photosensitization)
is anexcited state molecule formed
by direct energy tranfer between the excited sensitizer
. Less than 1% of triplet oxygen is
converted in parallel to superoxide anion(O
2). The formation
occurs via electron transfer via
productionof a sensitizer radical cation, or after an
intermediate reduction of the sensitizer
with asubstrate
followed by the single electron reduction of O
2 (Klotzet al.,
by oxidizing unsaturated
fatty acids and xenobiotics are cytochrome
P450 and the b5
Fanburg
, 2000). Electrons
leaking from nuclear membrane cytochrome oxidases and
electron transport systems may give rise to ROS. In addition
associated oxidases, aldehyde
dihydroorotate dehydrogenase, flavoprotein
dehydrogenase and tryptofan dioxygenase can all generate
dependent cell wall
like oxalate oxidases and amine oxidases
in the apoplast of
. Glycolate oxidase,
amino acid oxidase, urate oxidase, flavin oxidase, L
α
CoA oxidase are
2
O2 production in
. Auto
oxidation of
small molecules such as epinephrine, flavins, and
hydroquinones can also be an important source of intracellular
, 2004)
.
free radicals in the body is continuous and
inescapable. The basic causes include the following
Wilkins Instructor’s Resource
,
Immune system cells deliberately create oxy
-radicals and
oxygen species) as weapons.
producing cell generates continuously and
radicals and ROS as toxic waste. The cell
includes a number of metabolic processes, each of which can
produce different free
radicals. Thus, even a single cell can
produce many different kinds of free radicals.
4.3. Stress
The pressures common in industrial societies can trigger the
body's stress response to mass produce free radicals. The
stress response races the body's ener
increasing the number of free radicals as a toxic by
Moreover, the hormones that mediate the stress reaction in the
body -
cortisol and catecholamine
into particularly destructive free radicals.
4.4.
Pollution and other external substances
Air pollutants such as asbestos, benzene, carbon monoxide,
chlorine,formaldehyde, oz
one, tobacco smoke, and
toluene,Chemical
solvents such as cleaning products, glue,
paints, and paint thinners, Over
medications, Perfumes
, Pesticides
chloroform and other trihalomethanes caused by
chlorination,Cosmic radiation, Electromagnetic
and dental x-
rays, Radon gas, Solar radiation,the food
containing farm chemicals, like fertilizers and pesticides,
processed foods containing high levels of lipid peroxides, are
all potent generator of free radicals.
4.5. General factors: A
ging, Metabolism, Stress.
4.6. Dietary factors:
Additives, alcohol, coffee, foods of
animal origin, foods that have been barbecued, broiled,fried,
grilled, or otherwise cooked at high, temperatures, foods that
have been browned or burned, herbicides,hydro
vegetable oils, pesticides, sugar.
4.7. Toxins:
Carbon tetrachloride, Paraquat, Benzo (a) pyrene,
Aniline dyes, Toluene
4.8.Drugs:
Adriamycin, Bleomycin, Mitomycin C,
Nitrofurantoin, Chlorpromazine
Figure 2.
Free radical formation
5. Formation
of radicals in biological systems and
consequences ofoxidation of biological molecules
5.1.
Oxidative damage to protein and DNA
Proteins can be oxidatively
modified in three ways: oxidative
modification of specific amino acid, free radical mediated
peptide cleavage, and formation of protein cross
to reaction with lipid peroxidation products. Protein
containing amino acids such as methionine, cyst
International Journal of Innovation Sciences and Research
radicals. Thus, even a single cell can
produce many different kinds of free radicals.
The pressures common in industrial societies can trigger the
body's stress response to mass produce free radicals. The
stress response races the body's ener
gy-creating apparatus,
increasing the number of free radicals as a toxic by
-product.
Moreover, the hormones that mediate the stress reaction in the
cortisol and catecholamine
- themselves degenerate
into particularly destructive free radicals.
Pollution and other external substances
Air pollutants such as asbestos, benzene, carbon monoxide,
one, tobacco smoke, and
solvents such as cleaning products, glue,
paints, and paint thinners, Over
-the-counter and prescribed
, Pesticides
, Water pollutants suchas
chloroform and other trihalomethanes caused by
chlorination,Cosmic radiation, Electromagnetic
fields,Medical
rays, Radon gas, Solar radiation,the food
containing farm chemicals, like fertilizers and pesticides,
processed foods containing high levels of lipid peroxides, are
all potent generator of free radicals.
ging, Metabolism, Stress.
Additives, alcohol, coffee, foods of
animal origin, foods that have been barbecued, broiled,fried,
grilled, or otherwise cooked at high, temperatures, foods that
have been browned or burned, herbicides,hydro
genated
vegetable oils, pesticides, sugar.
Carbon tetrachloride, Paraquat, Benzo (a) pyrene,
Adriamycin, Bleomycin, Mitomycin C,
Nitrofurantoin, Chlorpromazine
Free radical formation
of radicals in biological systems and
consequences ofoxidation of biological molecules
Oxidative damage to protein and DNA
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, cyst
ein, arginine,
and histidine seem to be the most vulnerable to oxidation
(Freemanet al., 1982).
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 re
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
modific
ation 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 a
ctivity, heat stability, and
proteolysis susceptibility, which leads to aging.
5.2. Lipid peroxidation
Oxidative stress and oxidative modification of biomolecules
are involved in a number of physiological and
pathophysiological processes such as aging, a
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 radica
l 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, ischem
reperfusion injury, and diabetes (Lovell
et al
5.3. 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
major target (Wooet al., 1998).
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 (
Hattori
6. The important beneficial
role of free radicals
Generation of ATP (universal energy currency) from ADP
in the mitochondria: oxidative phosphorylation
Detoxification of xenobiotics by Cytochrome P450
(oxidizing enzymes)
Apoptosis of effete or defective cells
Killing of micro-
organisms and cancer cells by
macrophages and cytotoxic lymphocytes
International Journal of Innovation Sciences and
and histidine seem to be the most vulnerable to oxidation
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 re
active 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
ation 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
ctivity, 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, a
rtheroscleosis,
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,
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
l 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
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, ischem
ic
et al
., 1995).
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
Oxidative nucleotide as
deoxyguanosine is found to be
increased during oxidative damage to DNA under UV
radiation or free radical damage. It has been reported that
DNA are more susceptible to oxidative damage
that have role in many diseases including cancer. It has been
deoxyguanosine can be used as
Hattori
et al., 1997).
role of free radicals
Generation of ATP (universal energy currency) from ADP
in the mitochondria: oxidative phosphorylation
Detoxification of xenobiotics by Cytochrome P450
organisms and cancer cells by
macrophages and cytotoxic lymphocytes
Oxygenases (eg. COX: cyclo
lipoxygenase) for the generation of prostaglandins and
leukotrienes, which have many regulatory functions
(Yoshikawaet al., 2000)
Table 1.
Reactive oxygen and nitrogen species of biological
interest
7.Antioxidant
protection system
To protect the cells and organ systems of the body against
reactive oxygen species (ROS), 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 (Table 1)
Percival, 1998) these
components include:
7.1.1. Endogenous
Antioxidants
Bilirubin
Thiols, e.g., glutathione, lipoic acid, N
NADPH and NADH
Ubiquinone (coenzyme Q10)
Uric acid.
7.1.2. Enzymes
copper/zinc and manganese
dismutase
iron-dependent catalase
selenium-
dependent glutathione peroxidase
7.2. Dietary Antioxidants
Vitamin C
Vitamin E
Beta carotene and other carotenoids and oxycarotenoids,
e.g., lycopene and lutein
Polyphenols, e.g., flavonoids, flavones, flavonol’s, and
Proanthocyanidins
International Journal of Innovation Sciences and Research
Oxygenases (eg. COX: cyclo
-oxygenases, LOX:
lipoxygenase) for the generation of prostaglandins and
leukotrienes, which have many regulatory functions
Reactive oxygen and nitrogen species of biological
interest
protection system
To protect the cells and organ systems of the body against
reactive oxygen species (ROS), humans have evolved a highly
antioxidant protection system. It
involves a variety of components, both endogenous and
exogenous in origin, that function interactively and
synergistically to neutralize free radicals (Table 1)
(Mark
components include:
Antioxidants
Thiols, e.g., glutathione, lipoic acid, N
-acetyl cysteine
Ubiquinone (coenzyme Q10)
copper/zinc and manganese
-dependent superoxide
dependent glutathione peroxidase
Beta carotene and other carotenoids and oxycarotenoids,
Polyphenols, e.g., flavonoids, flavones, flavonol’s, and
221
7.3. Metal Binding Proteins
Albumin (copper)
Ceruloplasmin (copper)
Metallothionein (copper)
Ferritin (iron)
Myoglobin (iron)
f.Transferrin (iron)
8. Conclusion
Oxidative processes are essential to life, particularly for
obtaining the energy needed for various metabolic processes,
but they also serve as a source of ROS. Oxidation and
reduction processes are inseparable.
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