MODIFICATION OF HEPATIC DRUG-METABOLIZING-ENZYMES IN RAT FED NATURALLY-OCCURRING ALLYL SULFIDES

1. The effects of feeding allyl sulphides to rat (2000 ppm of the diet for 15 days) were investigated on various microsomal hepatic drug-met abolizing enzymes by their immunochemical detection and catalytic acti vity. 2. Allyl sulphides provoked a temporary dietary restriction, whi ch enhanced the microsomal level of P450 and the activities of NADH-cy tochrome c reductase and p-hydroxybiphenyl UDP-glucuronyltransferase ( UDPGT 2), and lowered the activities of p-nitrophenol hydroxylase (PNP H), N-nitrosodimethylamine demethylase (NDMAD), laurate omega-hydroxyl ase (LAH) and glutathione S-transferase (GST). Therefore, pair-fed ani mals were used as a more relevant control for the dietary effects of a llyl sulphides. 3. Diallyl sulphide (DAS) as well as diallyl disulphid e (DADS) produced an enhancement of the microsomal level of P4501A2, 2 B1/2 and 3A1/2, and epoxide hydrolase (EH) proteins, with an increase in the enzymatic activities they catalyse: ethoxyresorufin O-deethylas e (EROD), aryl hydrocarbon hydroxylase (AHH), methoxyresorufin O-demet hylase (MROD), ethoxycoumarin O-deethylase (FOOD), pentoxyresorufin O- depentylase (PROD), benzoxyresorufin O-debenzylase (BROD) and EH. Alth ough P4502E1 proteins were lowered on treatment, NDMAD activity was no t modified, and PNPH activity was even enhanced by allyl sulphides. On ly DAS treatment raised erythromycin N-demethylase (ERDM) activity. 4. Both DAS and DADS increased the activity of GST and p-nitrophenol UDP -glucuronyltransferase (UDPGT 1), whereas UDPGT 2 activity was enhance d only by DAS.