PROTECTIVE EFFECTS DIALLYL SULFIDE ON ACETAMINOPHEN-INDUCED TOXICITIES

Diallyl sulfide (DAS), a major flavour component of garlic, is known t o modulate drug metabolism and may protect animals from chemically ind uced toxicity and carcinogenesis. In this study the effects of DAS on the oxidative metabolism and hepatotoxicity induced by acetaminophen ( APAP) in rats were investigated In the hepatotoxicity evaluation of Fi scher 344 rats there was a dose-dependent increase in the odds of mort ality rate by APAP (P = 0.009); DAS treatment significantly protected rats from APAP-related mortality (P = 0.026). Liver toxicity determine d by lactate dehydrogenase activity was significantly increased by APA P treatment (0.75 g/kg). Pretreatment with DAS protected animals from APAP-induced liver toxicity in a time- and dose-dependent fashion. Tre atment of DAS (50 mg/kg) 3 hr after APAP dosing significantly (P < 0.0 5) protected rats from APAP-induced liver toxicity. The metabolism of APAP (50 mu M) in vitro was significantly inhibited by DAS (0.3-1 mM) in liver microsomes isolated from F344 rats. As the effect of DAS on A PAP-induced hepatotoxicity in vivo was observed only when DAS was admi nistered before or shortly after (<3 hr) APAP dosing, data suggested t hat the protective effect of DAS is mainly at the metabolic activation step of APAP. However, the possibility that DAS may also have effects -on other drug metabolism systems, such as glutathione (GSH) and gluta thione S-transferases, cannot be ruled out. Copyright (C) 1996 Elsevie r Science Ltd