Effects of Organotins on the Drug Metabolizing Enzymes in Fish

Abstract

Drug metabolizing enzymes play important roles in terrestrial and aquatic organisms for the synthesis, metabolism and excretion of various kinds of chemicals, especially lipophilic compounds including natural and synthetic chemicals. Drug metabolizing systems consist of two phases. In the first phase reaction, oxidative, reductive and hydrolytic reactions are dominant, and water solubility of chemicals increase through these processes. The toxicity of chemicals, however, are not necessarily decreased in the first phase and may be toxified in some cases through metabolic activation. In the second phase, conjugate reactions are dominant, and chemicals modified in the first phase are biotransformed to more water soluble compounds, and are readily excreted. These two-phase biotransformation processes are therefore important in the metabolism of lipophilic compounds such as endogenous steroids in the bodies of all animals, and also in the fates and effects of medicines in the medical and pharmaceutical fields. Since the 1970s, drug metabolizing enzymes have been found to be important in evaluating the toxicities of various lipophilic environmental pollutants, including pesticides and industrial chemicals. Although much knowledge has been accumulated on xenobiotic metabolism using experimental and wild animals, that obtained from aquatic organisms is insufficient for the complete understanding of fates of environmental chemicals incorporated in the body compared with mammals such as rats and mice. Many polycyclic aromatic hydrocarbons (PAHs) are known to induce cytochrome P450(CYP) and the metabolites act as potent carcinogens and/or mutagens and are, therefore, considered as important risk factors in epidemiological and epizootiological cancer. The P450 system is universally distributed in all organisms and plays a key role in the metabolism of xenobiotic compounds such as PAHs,