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

A possible role of metabolic activation by cytochrome P450 (P450) in thioac etamide-induced hepatotoxicity was investigated in male BALB/c mice. The mi ce were pretreated with the P450 inducer, beta-ionone, subcutaneously at 60 0 mg/kg, 72 and 48 h prior to an intraperitoneal administration of either 1 00 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 beta-ionone. Moreover, the po tentiation of thioacetamide-induced hepatotoxicity was also observed in the histopathological examination of livers. The hepatic necrosis by thioaceta mide was potentiated when mice were pretreated with beta-ionone. In liver m icrosomes, the activities of P450 2B-specific pentoxyresorufin O-depentylas e and benzyloxyresorufin O-debenzylase were significantly induced by the tr eatment with beta-ionone. beta-Ionone also induced other P450-associated mo nooxygenases. Because the pretreatment with beta-ionone was not hepatotoxic at the dose inducing P450s, our present results suggest that beta-ionone m ay be a useful model inducer of P450 enzyme(s) in studying toxic mechanism of certain chemicals which require metabolic activation by P450s in mice. ( C) 1999 Elsevier Science Ireland Ltd. All rights reserved.