Influence of starvation and acetone on the enzyme systems of biotransformation and toxicity of xenobiotics CYP2E1 substrates in rats
In experiments on 205 rats it was fixed, that starvation during 2–3 days, as well as introduction of acetone (250 and 1000 mg/kg) considerably increases CYP2Е1- dependent aniline and p-nitrophenol hydroxylase activity in the liver, kidneys, lungs and CYP3А dependent erythromycin N-demethylase activity, at the same time, suppress in a liver activity enzymes, dependent CYP2D, CYP1А2 and CYP2C as well as of activity UDP-glucuronosyltransferase, sulfotransferase and glutathione-S-transferase. The starvation causes accumulation of КоА and increases activity of N-acеtyltransferase in the liver. Starvation induces the change of enzymes activity and correlates with the intensifying of the processes of lipolysis, glycogenolysis, gluconeogenesis and, especially, ketogenesis which are appreciably initiated by introduction of acetone. The starvation and introduction of acetone increases metabolism of acetanilide and brombenzene, and, increasing the formation of toxic metabolites, raise its hepato-, nephro- and pulmotoxicity. The starvation attenuates elimination of indometacin from blood plasma, but intensifies conjugation of sulfadimidine with acetic acid.
Published at the site: 2004-02-02