Effects of antioxidant enzymes in the molecular control of reactive oxygen species toxicology

Reactive Oxygen Species (ROS) are produced during normal cellular function. ROS include hydroxyl radicals, superoxide anion, hydrogen peroxide and nitric oxide. They are very transient species due to their high chemical reactivity that leads to lipid peroxidation and oxidation of DNA and proteins. Under normal conditions, antioxidant systems of the cell minimize the perturbations caused by ROS. When ROS generation is increased to an extent that overcomes the cellular antioxidants the result is oxidative stress. It is now clear that several biological molecules, which are involved in cell signaling and gene regulation systems are very sensitive to redox statue of the cell. Antioxidants are substances that delay or prevent the oxidation of cellular oxidizable substrates. The various antioxidants exert their effect by scavenging superoxide, or by activating of a battery of detoxifying/defensive proteins. The prevention of oxidation is an essential process in all the aerobic organisms, as decreased antioxidant protection may lead to cytotoxicity, mutagenicity and/or carcinogenicity. This article also focuses on the mechanisms by which antioxidants and xenobiotics induce the gene expression of detoxifying enzymes. On the other hand, small molecules that mimic antioxidant enzymes are becoming new tools for the treatment of many diseases. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.