Effects of antioxidant enzymes in the molecular control of reactive oxygenspecies toxicology

Reactive Oxygen Species (ROS) are produced during normal cellular function. ROS include hydroxyl radicals, superoxide anion, hydrogen peroxide and nit ric oxide. They are very transient species due to their high chemical react ivity that leads to lipid peroxidation and oxidation of DNA and proteins. U nder normal conditions, antioxidant systems of the cell minimize the pertur bations caused by ROS. When ROS generation is increased to an extent that o vercomes the cellular antioxidants the result is oxidative stress. It is no w clear that several biological molecules, which are involved in cell signa ling and gene regulation systems are very sensitive to redox statue of the cell. Antioxidants are substances that delay or prevent the oxidation of ce llular oxidizable substrates. The various antioxidants exert their effect b y scavenging superoxide, or by activating of a battery of detoxifying/defen sive proteins. The prevention of oxidation is an essential process in all t he aerobic organisms, as decreased antioxidant protection may lead to cytot oxicity, mutagenicity and/or carcinogenicity. This article also focuses on the mechanisms by which antioxidants and xenobiotics induce the gene expres sion of detoxifying enzymes. On the other hand, small molecules that mimic antioxidant enzymes are becoming new tools for the treatment of many diseas es. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.