MODIFICATION OF HEPATIC DRUG-METABOLIZING-ENZYMES IN RATS TREATED WITH ALKYL SULFIDES

Natural compounds which elevate detoxification enzymes and/or reduce a ctivating enzymes could be considered as good candidates to protect ag ainst cancer. In this work, we studied the modulation of hepatic drug- metabolizing enzymes in rats treated with dimethyl sulfide (DMS), dime thyl disulfide (DMDS), methylpropyl disulfide (MPDS), dipropyl sulfide (DPS), dipropyl disulfide (DPDS) and diallyl disulfide (DADS) issued from Allium species. Compounds containing methyl groups had little or no effect. Compounds with two propyl groups or two allyl groups provok ed a pleiotropic response on drug-metabolizing enzymes. DPS, DPDS and DADS induced ethoxyresorufin O-deethylase, methoxyresorufin O-demethyl ase and mostly pentoxyresorufin O-depentylase and decreased nitrosodim ethylamine N-demethylase and erythromycin N-demethylase. These modific ations of enzyme activities were accompanied by an increase of CYP 2B1 ,2 and a decrease of CYP 2E1, evidenced by immunoblotting. The same tr eatments stimulated some phase II enzyme activities such as glutathion e transferase and UDP-glucuronyl transferases. This pattern of inducti on and/or inhibition of drug metabolizing enzymes was qualitatively si milar to that elicited by the enzyme inducer, phenobarbital. The magni tude of the effects produced by DPDS was smaller than those produced b y DADS and DPS. Our results suggest a possible protective effect of al kyl sulfides as well as diallyl disulfide, on the first step of carcin ogenesis via the modulation of enzymes involved in carcinogen metaboli sm. (C) 1997 Elsevier Science Ireland Ltd.