Jeong T C, Gu H K, Park J I, Yun H I, Kim H C, Ha C S, Roh J K
Toxicology Research Center, Korea Research Institute of Chemical Technology, Taejon, South Korea.
Toxicol Lett. 1999 Mar 8;105(1):39-46. 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, beta-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 beta-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 beta-ionone. In liver microsomes, the activities of P450 2B-specific pentoxyresorufin O-depentylase and benzyloxyresorufin O-debenzylase were significantly induced by the treatment with beta-ionone. Beta-ionone also induced other P450-associated monooxygenases. Because the pretreatment with beta-ionone was not hepatotoxic at the dose inducing P450s. our present results suggest that beta-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.
在雄性BALB/c小鼠中研究了细胞色素P450（P450）介导的代谢活化在硫代乙酰胺诱导的肝毒性中的可能作用。在腹腔注射100或200mg/kg硫代乙酰胺前72小时和48小时，给小鼠皮下注射600mg/kg的P450诱导剂β-紫罗兰酮进行预处理。硫代乙酰胺引起的血清丙氨酸转氨酶和血清天冬氨酸转氨酶活性升高，经β-紫罗兰酮预处理后大大增强。此外，在肝脏组织病理学检查中也观察到硫代乙酰胺诱导的肝毒性增强。当用β-紫罗兰酮预处理小鼠时，硫代乙酰胺引起的肝坏死增强。在肝微粒体中，用β-紫罗兰酮处理可显著诱导P450 2B特异性戊氧基试卤灵O-脱戊基酶和苄氧基试卤灵O-脱苄基酶的活性。β-紫罗兰酮还诱导其他与P450相关的单加氧酶。由于在诱导P450的剂量下，用β-紫罗兰酮预处理对肝脏没有毒性，我们目前的结果表明，在研究某些需要P450进行代谢活化的化学物质在小鼠体内的毒性机制时，β-紫罗兰酮可能是一种有用的P450酶模型诱导剂。
