Pretreatment of male BALB/c mice with β-ionone potentiates thioacetamide-induced hepatotoxicity

A possible role of metabolic activation by cytochrome P450 (P450) in thioacetamide-induced hepatotoxicity was investigated in male BALB/c mice. The mice were pretreated with the P450 inducer, β-ionone, subcutaneously at 600 mg/kg, 72 and 48 h prior to an intraperitoneal administration of either 100 or 200 mg/kg of thioacetamide. The elevated activities of serum alanine aminotransferase and serum aspartate aminotransferase by thioacetamide were greatly potentiated by the pretreatment with β-ionone. Moreover, the potentiation of thioacetamide-induced hepatotoxicity was also observed in the histopathological examination of livers. The hepatic necrosis by thioacetamide was potentiated when mice were pretreated with β-ionone. In liver microsomes, the activities of P450 2B-specific pentoxyresorufin O-depentylase and benzyloxyresorufin O-debenzylase were significantly induced by the treatment with β-ionone. β-Ionone also induced other P450-associated monooxygenases. Because the pretreatment with β-ionone was not hepatotoxic at the dose inducing P450s, our present results suggest that β-ionone may be a useful model inducer of P450 enzyme(s) in studying toxic mechanism of certain chemicals which require metabolic activation by P450s in mice.