Gerych O. Oxidative and conjugative reactions of biotransformation of xenobiotics incondition of metabolic disoders, induced diabetes mellitus and high-fatty diet.

Work is devoted to study the state of the system of biotransformation of xenobiotics at diabetes and overload of ration by fats in rats. Different severity diabetes and use of high-fatty diet during 4 weeks are caused growth of activity of cytoсhromes Р4502E1 and Р4503A, activity of arylesterase, arylamidase and aliesterase, activity of UDP-glucuronosyl transferase. At the same time both states are caused inhibition of activ-ity of multiple cytochrome P450 isoforms (Р4501А2, 2В, 2С and 2D), alcogole dehydrogenase, phenol sulfotransferase. At diabetes activities of aldehyde dehydrogenase and -, - and -forms of glutathione-S-transferase, N-acеtyl transferase were decreased, while at an overload fats activities of these enzymes were increased. The changes of en-zymes activities are considerably associated with activating of ketogenesis, gluconeogene-sis and lipolysis processes. This cause the redistribution of basic ways of metabolism of model xenobiotics. Diabetes and high-fat diet have effect upon the cytoсhrome of Р4503A-N-demethylase reaction of amidopyrine. However diabetes inhibits acеtylation of 4-аmioantipyrine and sulfadimezine, and high-fatty diet activate these reactions. Different severity diabetes and high-fat diet activate reactions of biotransformation of acetanilide, toluene and bromobenzene, catalyzed with СУР2Е1. Diabetes and overload by fats increased bromobenzene hepatotoxicity and sodium diclofenac analgesic activity. In rats with overload fats paracetamol hepatotoxicity was in-creased.