Effect of desoxycorticosterone on the activity of drug-metabolizing enzyme systems

Abstract

Single administration of desoxycorticosterone acetate (DOCA) in a dose of 50 mg/kg body mass intramuscularly in male Wistar rats revealed dose-dependent potentiation of hexobarbital sleeping time and inhibition of the activity of the oxidases with mixed functions in substrates of types I (hexobarbital, ethylmorphine) and II (aniline), although this is not accompanied by changes in the components of the electron-transport chain. It is assumed that DOCA may possibly inhibit the metabolism of the above mentioned substrates, being an alternative substrate of oxidases with mixed functions. In an acute experiment DOCA does not influence the activity of esterases (liver esterase A and intestinal esterase B), but the compound has an inhibitory effect on some synthetase reactions--cytosol glutathione-S-transferase. Repeated administration of DOCA for 3-27 days in doses of 10 and 20 mg/kg i.m. does not have an enzyme-inducing effect. There are no significant changes in the oxidases with mixed functions and in the content of cytochrome P-450. The effects of DOCA on drug metabolism after a single and after repeated application are compared with the effects of hydrocortisone.