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Role of Oxidative Stress in Biological Systems

Article · December 2019

DOI: 10.23884/mejs.2019.5.2.07

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Middle East Journal of Science (2019) 5(2):155 - 162

Middle East Journal of Science

INTERNATIONAL
https://dergipark.org.tr/mejs
ENGINEERING,
SCIENCE AND e-ISSN:2618-6136 DOI: 10.23884/mejs.2019.5.2.07 MEJS
EDUCATION GROUP
Review

ROLE OF OXIDATIVE STRESS IN BIOLOGICAL SYSTEMS

Additiya PARAMANYA , Ahmad ALI*

Department of Life Sciences, University of Mumbai, Vidyanagari, Santacruz (East), Mumbai, Maharashtra,
INDIA
*Corresponding author: [email protected]

Abstract: Oxidative stress is a phenomenon wherein there is an imbalance between the rate of oxidant
formation and its elimination from the body. It has been known to be a promoting factor of various acute
and chronic diseases, some of which are lethal. Oxidative stress usually occurs when the generation of
oxidants, as a byproduct of the metabolic processes is much higher than usual. However, several
exogenous sources such as pollution and alcohol have been known to be major factors in oxidative
stress. Although the human body produces several antioxidants their inadequacy can be combatted by
the consumption of food rich in antioxidants. The following review briefly highlights the generation of
free radicals in the body, their effect on biomolecules and the role of oxidative stress in the human body.

Keywords: antioxidants, glycoxidative damage, Oxidative stress, reactive oxygen species (ROS),
reactive nitrogen species (RNS)
Received: December 3, 2019 Accepted: December 27, 2019

1. Introduction

Oxygen is the most vital element required for life. The process of oxidation-reduction during
metabolism generates free radicals or oxidants. The balance between the rate of oxidant formation and
their elimination is essential for the systematic functioning of biological processes [1]. An imbalance in
this rate may be caused due to a certain disturbance in the endogenous system or exogenous factors such
as unhealthy diet, smoking, medicinal side-effects, etc. This phenomenon of imbalance has been called
oxidative stress [2].
Oxidants can be grouped as radicals and non-radicals. Both reactive oxygen species (ROS), as
well as reactive nitrogen species (RNS), can exist in radical and non-radical form. Radicals can exist
independently and contain one or more unpaired electron in the valence shell. Superoxide (O2-), Peroxyl
radical (ROO∙), Alkoxy radicals (RO∙), Nitric oxide (nitrogen monoxide) (NO∙), Nitrogen dioxide (NO∙2)
and Hydroxyl (-OH) ions are some of the examples of radical oxidants [2, 3]. They are highly reactive
and attain stability either by donating or accepting electrons, whereas non-radical oxidants are lesser
reactive but participate in free radical reactions. Nonradical oxidants include Hydrogen peroxide (H2O2),
Hypochlorous acid (HOCl), Ozone (O3), Singlet oxygen (1O2), Nitrous acid (HNO2), Organic peroxides
(ROOH), Aldehydes (HCOR), Peroxynitrite (ONOOH), etc [1,3].
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2. Generation of Free Radicals

Free radicals may be generated inside the body, i.e. endogenously as a by-product of aerobic
metabolism while exogenous sources can be related to the individual's lifestyle and environment
(Fig.1.). During normal metabolism, each cell produces approximately 20 billion oxidants per day. The
insufficient reduction of oxygen in mitochondria during the electron transport chain (ETC) can lead to
the formation of hydrogen peroxide and hydroxyl radicals. As a self-defense mechanism, white blood
cells produce nitric oxide (NO), superoxides and H2O2 to combat with the pathogenic microorganisms.
Moreover, during the degradation of fatty acids, peroxisomes may produce hydrogen peroxide as by-
products. Usually, this hydrogen peroxide is degraded in the cell by catalase. However, under certain
conditions, it might escape the catalysis and contribute to oxidative stress. Furthermore, cytochrome
P450 enzymes produce oxidant as a defense against ingested toxic chemicals [4].

The exogenous sources may include inhalation of free radicals present in the environment from
ionizing radiations (Ultraviolet light), automobile exhaust (mainly ozone and nitrous oxide), burning of
certain substances, etc. These factors have been known to lower the level of antioxidants in the body
thereby contributing to oxidative stress [4]. Exposure to air pollution or smoke generates oxygen radicals
while breathing. Cigarette smoking (active or passive), consumption of alcohol and unsaturated fat may
put at risk the natural antioxidant system in the body thereby contributing to oxidative stress [1, 4].

Generation of
free radicals

Endogenous Exogenous
sources sources

White Smoking
Mitochond Peroxisom Unsaturate
Blood Cells and Pollution
ria es d fats
(WBC) Alcohol

Figure 1. Sources for the generation of free radicals in the human body

3. Mechanism of action of free radicals

Most of the biomolecules and biochemical processes are affected by free radicals. However, the
three major classes of biomolecules, i.e. nucleic acids, proteins, and lipids are severely affected by
oxidative stress. These oxidized biomolecules may independently or simultaneously contribute to
diseases affecting human health [5].

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3.1. Nucleic acid

Since ROS is generated in mitochondria, the susceptibility of oxidative damage to the
mitochondrial DNA is higher than nuclear DNA. Nitrogenous bases, as well as deoxyribose sugar, are
adversely affected creating single and double-stranded breaks. Several adducts are formed by the attack
of OH• radicals on purine and pyrimidine such as 5-hydroxy-6-hydro-cytosine, 8-hydroxydeoxy
guanosine, 5-formyl uracil, etc. Of all the free radical-induced adducts, the presence of 8-hydroxydeoxy
guanosine indicates oxidative DNA damage [3, 5].
Due to the single-stranded structure, RNA is more adversely affected by oxidative stress than
DNA. The most studied adduct of RNA is the 7, 8-dihydro-8-oxo-guanosine (8-oxoG) and its linkage
has been established with Alzheimer's, Parkinson's and other neurodegenerative diseases [2, 5].
3.2. Proteins
ROS mediated protein oxidation is usually determined by the presence of carbonyl groups.
Different amino acids in the protein might get affected leading to conformational changes which may
alter or decrease the function of the oxidized proteins [3, 4].
3.3. Lipids
Membrane lipid peroxidation is one of the conditions which may lead to a series of disorders. The
decrease in membrane fluidity is observed during lipid peroxidation which further leads to the
inactivation of membrane-bound proteins [4].
4. Effect of oxidative stress on human health
Oxidative stress has been known to promote the induction of several acute and chronic disorders
some of which may be degenerative or fatal (Table.1).
4.1. Cancer
Oxidative stress can cause direct damage to various biomolecules. Oxidative DNA damage has
now been proven to be a prerequisite in chromosomal abnormalities and oncogene activation thereby
causing tumor genesis and/or carcinogenesis [6]. DNA-protein crosslinks, deformity in sugar and base
structure are few of the structural changes induced by ROS. According to Hattori et al., 8-hydroxy-2-
deoxyguanosine is a suitable biological marker for oxidative stress. Incessant oxidative stress may affect
the proteome to cause an alteration in the protein structure [7]. This may generate abnormalities in the
structure and function of the proteins such as phosphatases and kinases, Loss, gain or switch in function
of these enzymes lead to uncontrolled cell growth [8]. Oxidative stress has been correlated with cancer
mainly of the breast, colon and prostate [4].
4.2. Cardiovascular diseases
Oxidative stress acts as a triggering component for the formation of cholesterol plaque in the walls
of arteries. This condition is called atherosclerosis and cause an obstruction in the blood flow [9].
Moreover, augmented levels of superoxide anions have been reported to have a direct effect on the
pathogenesis of atherosclerosis. One of the theories suggests that these superoxide anions cause
oxidative modifications in low-density lipoproteins (LDL) leading to atherosclerotic lesions and lipid
accumulation [10].
4.3. Diabetes
High level of sugar in blood or hyperglycemia is known to elevate ROS levels leading to
discrepancies in the normal functioning of metabolic pathways. One such example is the decrease in the
activity of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) which is one of the key enzymes of

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one of the major carbohydrate catabolism, i.e. Glycolysis, by modifying it with ADP-ribose polymers
[11]. The islets β-cells of the pancreas get adversely affected when interacted with hydrogen peroxide
and superoxide anions that cause lower or inefficient insulin activity [12].
4.4. Inflammation
Activation of transcription factors like NF-kappa B causes inflammation when stimulated by
oxidants. Biswas has stated inflammation and oxidative stress to be a tightly linked pathophysiological
process wherein one can act as the inducing factor for the other [13].
Endothelial dysfunction and tissue injury can occur at the site of inflammation with an increased
number of ROS [14]. This can be exemplified with the pathogenesis of rheumatoid arthritis, the chronic
inflammation of joints and the surrounding tissues, which is caused due to the formation of ROS and
RNS at the inflammatory site [15].
4.5. Neurodegenerative disorders
The high lipid content, as well as a high level of oxygen consumption by the Central Nervous
System (CNS), increases its susceptibility to oxidative stress. The decrease in membrane fluidity by
lipid peroxidation increases the permeability of Ca2+ which affects the triggering of neurotransmitter
release [16]. Huntington's, Alzheimer's, Parkinson's disease, amyotrophic lateral sclerosis (ALS),
memory loss, depression, and multiple sclerosis are some of the few diseases resulting from oxidative
stress [1, 5].
4.6. Obesity
A decrease in vasodilatory response to acetylcholine in obese patients has been observed as a
result of the induction of oxidative stress [17]. Overweight leads to irregularity in the function of adipose
tissue, which in turn facilitates hyperglycemia acting as a contributing factor in type-2 Diabetes mellitus
[18]. Furukawa et al. propose that the chance of obesity-associated metabolic syndrome is proportional
to the increase in the level of oxidative stress [19].
4.7. Respiratory diseases
Inflammation of the respiratory tract has been associated with periodic worsening of asthma. It
has been observed that there has been an increase in hydrogen peroxide and isoprostanes levels in
sputum and exhaled air during an allergic reaction [20].

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Table 1. Diseases caused due to Oxidative stress

Disease/ Disorder Particulars References

Cancer Colorectal, breast, prostate [5, 6]

Cardiovascular Atherosclerotic lesions and lipid accumulation [9, 10]

diseases

Diabetes Lower or inefficient insulin activity [11, 12]

Inflammation Endothelial dysfunction and tissue injury, [13, 14]

Rheumatoid arthritis

Neurodegenerative Huntington’s, Alzheimer's, Parkinson's disease, [4, 16]

disorders
ALS, memory loss, depression, multiple
sclerosis

Obesity Obesity-associated metabolic syndrome [17, 18]

Respiratory Asthma [20]

diseases

5. Antioxidants
Antioxidants are the substances that help to maintain the stability in oxidative stress by preventing
oxidation [21]. The human body produces a wide range of antioxidants which can be grouped into
enzymatic and non-enzymatic antioxidants (Figure 2).
Superoxide dismutase or SODs (EC 1.15.1.11), catalases (EC 1.11.1.6) and glutathione
peroxidase or GSH-Px (EC 1.11.1.9) are the major enzymatic antioxidants in the body. SODs are widely
expressed in the lungs and help in the dismutation of superoxides. Of the three types of SODs, MnSOD
and CuZn-SOD are expressed in mitochondrial and extracellular matrix respectively, while certain
SODs are expressed extracellularly and hence called EC-SOD. Catalases and GSH-Px help in the
reduction of H2O2 produced during the action of SODs or during ETC [21, 22].

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•Superoxide dismutase or
SODs
Enzymatic
antioxidants
•Catalases
•Glutathione Peroxidase
or GSH-Px

•Vitamin C
Non- •Vitamin E
enzymatic •Β-carotene
antioxidants •Phytochemicals (like
ascorbic aid, ferulic acid, etc)

Figure 2. Types of antioxidants

Vitamin C is one of the important non-enzymatic antioxidants in the body. Being water-soluble,
it provides an aqueous phase for free radical scavenging. α-Tocopherol OR Vitamin E is a membrane-
bound active form of vitamin E antioxidant which inhibits free radical formation. Phytochemicals in the
plant have been proven to show antioxidant activity. Β-carotene acts as an effective antioxidant against
peroxyl (ROO•), hydroxyl (•OH), and superoxide (O2−.) radicals [22, 23]. The phytochemicals are being
tested for suitability as it appears to be a promising candidate for antioxidant supplements [23].
6. Conclusion
Over-production of oxidants or unavailability of antioxidants can cause an imbalance in the free
radical generation and their detoxification leading to oxidative stress. Oxidative stress seems to be
playing a major role in inflammation that further acts as a contributing factor to a plethora of diseases.
The human body can combat oxidative stress by maximizing the availability of natural antioxidants.
However, antioxidants can be supplemented to the human body from a wide range of drugs synthesized
from chemical as well as natural sources. However, being environmentally friendly, natural antioxidants
like phytochemicals are considered to be more convenient and safer for consumption.

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