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 couples¹. Free radicals cause a chain reactions leading to consecutive oxidation. These radicals attack molecules like fat, protein, DNA, sugar etc². 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 harmless³.

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 environment is preserved by enzymes that maintain the reduced state through a constant input of metabolic energy⁷.

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 peroxides⁸.

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 Ca²⁺- 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 electrons⁹.

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 started¹⁰.

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 DNA¹¹.

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.

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 repair¹².

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 material¹³.

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; various spices such as cardamom, cinnamon, clove, coriander, ginger, dill, garlic etc; neem etc¹⁴.

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 cancer¹⁵.

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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Received on 24.02.2011 Accepted on 25.05.2011

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

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