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

• Published in: Toxicology letters Vol. 105; no. 1; pp. 39 - 46
• Main Authors: Cheon Jeong, Tae, Kyoung Gu, Hee, Park, Jong-Il, Yun, Hyo-In, Kim, Hyoung-Chin, Ha, Chang-Su, Roh, Jung Koo
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 08.03.1999; Amsterdam Elsevier Science
• Subjects: Alanine Transaminase - blood; Animals; Aspartate Aminotransferases - blood; Biological and medical sciences; Carcinogens - toxicity; Chemical and Drug Induced Liver Injury - enzymology; Chemical and Drug Induced Liver Injury - pathology; Chemical and industrial products toxicology. Toxic occupational diseases; Cytochrome P-450 Enzyme System - biosynthesis; Drug Synergism; Enzyme Induction - drug effects; Hepatotoxicity; Isoenzymes - biosynthesis; Liver - enzymology; Liver - pathology; Liver Function Tests; Male; Medical sciences; Mice; Mice, Inbred BALB C; Microsomes, Liver - drug effects; Microsomes, Liver - enzymology; Norisoprenoids; P450 induction; Potentiation; Pretreatment; Terpenes - toxicity; Thioacetamide; Thioacetamide - toxicity; Toxicology; Various organic compounds; β-Ionone; Potentiation; β-Ionone; Thioacetamide; Pretreatment; P450 induction; Hepatotoxicity; Terpenoid; Poison interaction; Toxicity; Cytochrome P450; Rodentia; Hepatic disease; Ketone; Toxic association; Vertebrata; Mammalia; Mouse; Thioamide; Animal; Digestive diseases; Mechanism of action; Enone
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/S0378-4274(98)00386-5

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.