Xenobiotics, Oxidative Stress, Free Radicals Vs. Antioxidants ...

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Xenobiotics, Oxidative Stress, Free Radicals Vs. Antioxidants ...

Asian J. Res. Pharm. Sci. 2011; Vol. 1: Issue 2, Pg 36-38 [AJPSci.]

ISSN- 2231–5640 (Print) www.asianpharmaonline.org

ISSN- 2231–5659 (Online) 0974-3618

REVIEW ARTICLE

Xenobiotics, Oxidative Stress, Free Radicals Vs. Antioxidants: Dance Of

Death to Heaven’s Life.

Dibyajyoti Saha* and Ankit Tamrakar

School of Pharmacy, Chouksey Engineering College, Lal Khadan, Masturi Road, Bilaspur-495004, C.G.

*Corresponding Author E-mail: saha.dibyajyoti@gmail.com

ABSTRACT:

A xenobiotic is a compound that is foreign to the body. Xenobiotics can produce a variety of biological effects,

including pharmacologic responses, toxicity, genes, immunologic reactions and cancer. Oxidative stress is a leading

cause to damage cells by oxidation. The rate at which oxidative damage is induced (input) and the rate at which it is

efficiently repaired and removed (output). A free radical is an atom or molecule that has one or more unpaired

electron(s). These are highly reactive species capable of wide spread, indiscriminate oxidation and peroxidation of

proteins, lipids and DNA which can lead to significant cellular damage and even tissue and/or organ failure.

Antioxidants are molecules that slow or prevent the oxidation other chemicals. Oxidation reactions can involve the

production of free radicals which can form dangerous chain reactions. Antioxidants can terminate these chain reactions

by removing radical intermediates and can inhibit other oxidation reactions by being oxidized themselves.

Antioxidants are often reducing agents such as thiols or phenols. Therefore, we need antioxidants to ensure our

defence mechanism for neutralizing harmful radicals.

KEYWORDS: Xenobiotics, Oxidative stress, Free radicals, Antioxidants, Polyphenolic compounds.

INTRODUCTION:

Xenobiotics are chemical compounds foreign to the body;

such as drugs, food additives, environmental pollutants;

more than 200,000 have been identified and they are

metabolized into two phases. Oxidative stress is a large

increase in the cellular reduction potential, or a large

decrease in the reducing capacity of the cellular redox

couples 1 . Free radicals cause a chain reactions leading to

consecutive oxidation. These radicals attack molecules like

fat, protein, DNA, sugar etc 2 . Antioxidants are beneficial

components that neutralize free radicals before they can

attack cell proteins, lipids and carbohydrates. The

mechanism involves significant inhibition or delay in the

oxidative process. Biochemist and epidemiologists have

stated the antioxidants neutralize free radicals by binding

their lonely electrons and rendering them harmless 3 .

Received on 24.02.2011 Accepted on 25.05.2011

© Asian Pharma Press All Right Reserved

Asian J. Res. Pharm. Sci. 1(2): April-June 2011; Page 36-38

36

XENOBIOTICS:

The principal classes of xenobiotics of medical relevance

and drugs, chemical carcinogens and various compounds

that have found their way into our environment by one

route or another, such as polychlorinated biphenyls and

certain insecticides.

Xenobiotics are metabolized into two phases. The major

reaction of phase-I is hydroxylation catalyzed by a variety

of monooxygenases, also known as cytochrome P450s. In

phase 2, the hydroxylated species are conjugated with a

variety of hydrophilic compounds such as glucuronic acid,

sulfate or gluthione. The combined operation of these two

phases renders lipophilic compounds into water soluble

compounds that can be eliminated from the body.

Cytochrome P450s catalyze reactions that introduce one

atom oxygen delivered from molecular oxygen into the

substrate, yielding a hydroxylated product.

Xenobiotics may be occurring some biological effects such

as pharmacologic responses, genes, toxicity, immunologic

reactions and cancer 4-6 .

OXIDATIVE STRESS:

Oxidative stress is a leading cause to damage cells by

oxidation. All forms of life maintain a reducing

environment within their cells. The cellular redox


Asian J. Res. Pharm. Sci. 2011; Vol. 1: Issue 2, Pg 36-38 [AJPSci.]

environment is preserved by enzymes that maintain the

reduced state through a constant input of metabolic energy 7 .

The effects of oxidative stress depend upon the size of

changes, with a cell being able to overcome small

perturbations and regain its original state. A particularly

aspect of oxidative stress is the production of reactive

oxygen species, which include free radicals and peroxides 8 .

Oxidative stress is imposed on cells as a result of one of

three factors:

a. An increase in oxidant generation;

b. A decrease in antioxidant protection;

c. A failure to repair oxidative damage.

Pathways:

a. Oxidative stress – DNA damage.

b. Oxidative stress – GSH depletion.

c. Oxidative stress – Direct damage to proteins – Rises in

intracellular free Ca 2+ - Cytoskeletal damage.

d. Oxidative stress – Rises in intracellular free iron –

Membrane peroxidation and destruction – Injury to adjacent

cells.

e. Oxidative stress – Increased lipid peroxidation –

Increased damage to DNA, proteins, lipids.

FREE RADICALS:

The father of free radical research, Dr. Denham Harman,

proposed his free radical theories in 1956. Free radicals are

atoms or molecules containing an odd number of electrons,

which results in an odd electron in the external orbit. Free

radicals frantically seek electrons in order to pair their

unpaired electrons 9 .

Free radicals cause a chain of reactions loading to

consecutive oxidation. These radicals attacks molecules like

fat, proteins, DNA, sugar etc. the newly damaged molecule

unfortunately becomes a free radicals and thus a chain

reaction started 10 .

Free radicals are generated during normal metabolism and

exposure to environmental insults such as infections agents,

pollution, UV light, radiation and so on. These are highly

reactive species capable of wide spread, indiscriminate

oxidation and peroxidation of proteins, lipids and DNA

which can lead to significant cellular damage and even

tissue and/or organ failure. When these harmful free

radicals cause damage to vital proteins, lipids and DNA 11 .

Cancer Pathways:

Increase of free radicals – oxidative damage – DNA

damage – Cancer.

Free Radicals Cause Oxidative Stress:

• Superoxide anion radicals.

• Hydrogen peroxide.

• Hydroxyl radicals.

• Peroxy radicals.

• Nitric oxide radicals.

37

Formation of Free Radicals:

• Air pollution.

• Cigarette, pipe smoke.

• Injury and inflammatory response.

• Ionization radiation.

• Ischemia.

• Cellular metabolism (electron transport chain).

• Exercise.

• Food additives.

• Food preparation.

• Ozone.

• Pesticides.

• Other pollution.

Stress.

• Sunlight.

• X-rays.

ANTIOXIDANTS:

Antioxidants are molecules that slow or prevent the

oxidation (other chemicals). Antioxidants are termed as

reducing agents and affect cell differentiation and

proliferation, block nitrosamine formation, stimulate the

immune system, help to maintain the integrity to cell

membrane and matrix, aid in the maintenance of normal

DNA repair 12 .

General Classification:

• Primary antioxidants: Terminate free radical chain

reactions e.g. Phenolic compounds, Tocopherol, Tertiary

amine, Flavonoids.

• Oxygen scavengers: It is react with oxygen and remove

it e.g. Ascorbic acid and its derivatives.

• Secondary antioxidants: It decomposes lipid peroxides

into stable products (sulphur compounds, seleno –

compounds).

• Enzymatic antioxidants: It remove highly oxidative

species (superoxide dimutase, catalase, glutathione per

oxidase)

• Chelating agents: These are chelate metallic ions such

as copper and iron; (citric acid, phytic acid) etc.

There are many example of antioxidants:

• Intracellular enzymes: SOD, GSP.

• Endogenous molecules: GSH, Thioredoxin.

• Essential nutrients: Vitamin C, Vitamin E, Selenium.

• Dietary compounds: Bioflavonoid, Proanthocyanidans.

Plants as Antioxidants:

Recently there has been an increased interest in the food

industry and in preventive medicine in the development of

‘natural antioxidants’ from plant material 13 .

Natural antioxidants are found in various vegetables such as

carrot, beat, tomato, lotus, cauliflower, cabbage, capsicum

etc; green tea leaves; grapes and wines; soya beans; citrus

peel; sesame seed; cocoa seed; grapes and wines; willow

tree; grape stems; orange and apple fruits; barley and malt

grains; olives; ashwagandha; rhubarb; Virginia skullcap;


Asian J. Res. Pharm. Sci. 2011; Vol. 1: Issue 2, Pg 36-38 [AJPSci.]

various spices such as cardamom, cinnamon, clove,

coriander, ginger, dill, garlic etc; neem etc 14 .

Polyphenolic compounds as Antioxidants:

Plant polyphenols are well known antioxidants. This term

includes phenolic acids, flavonols, proanthocyanidins and

anthocyanins which are responsible for many properties of

fruit juices and fermented beverages. They may be

contribute to explain the general protective effects of fruit

and vegetable consumption against cancer 15 .

Utility of Antioxidants:

• Boost the immune system.

• Clear and purify the blood.

• Protect the cell integrity as well as supportive collagen

tissue.

• Useful for detoxification process (in alcoholic cases).

• Prevent allergies.

• Prevent arthritis and joint pain.

• Prevent cancer disease.

• Prevent fatty deposits, piles and varicose veins.

• Maintaining elasticity of the veins and good

circulation.

• Prevents colds and flu.

• Prevent fatigue and memory loss.

• Useful for mouth ulcers, gum bleeding and gingivitis

(vitamin C).

• Stamina enhancer.

• Reduce stress.

• Prevent infections and wounds, injuries.

• Male infertility.

• Help to promote growth of tissue and helps prevent

DNA destruction.

CONCLUSION:

Lastly; the xenobiotics, oxidative stress and free radicals are

not measured by body’s defence mechanism and they may

cause damage to vital proteins, lipids and DNA. Therefore,

we need antioxidants to ensure our defence mechanism for

neutralizing harmful radicals.

All antioxidants have a chemical element referred to as a

“redox” potential, which is the measurement of their ability

to be oxidized. Considering the fact that the redox

equilibrium is important to the body’s coping mechanism, it

follows that antioxidants can influence many health

conditions.

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