Protective effect of rifampicin against acute liver injury induced by carbon tetrachloride in mice
Protective effect of rifampicin against acute liver injury induced by carbon tetrachloride in mice
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DOI：
10.1254/jjp.69.325
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发表时间：
1995-12-01
期刊：
影响因子：
--
通讯作者：
Inoue, K
中科院分区：
文献类型：
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作者：
Huang, RB;Okuno, H;Inoue, K
利福平对四氯化碳（CCl 4）诱导的肝损伤具有显著的保护作用。利福平（200 mg/kg）预处理小鼠血清谷丙转氨酶（ALT）和谷草转氨酶（AST）活性无明显变化，仅出现肝细胞脂肪变性，而肝小叶中心坏死严重，血清ALT和AST活性分别高达281和271 I.U./对照组给予CCl_4（400 μ l/kg）后，分别为1.5mg/kg和1.5mg/kg。利福平预处理组大鼠肝微粒体药物代谢酶的含量和活性也明显高于对照组。CCl 4介导。在利福平处理的肝微粒体中，丙二醛（MDA）形成增加，表明利福平能够增加P-450 2 E1催化的CCl 4的NADPH依赖性代谢，以产生自由基。然而，在体外细胞色素P-450（P-450）酶系统中，利福平在2 - 32 × 10（-6）M的不同浓度下明显抑制MDA的形成。另一方面，NADPH氧化代谢中的四氯化碳和苯胺羟基化没有抑制利福平的存在下，在这个系统中，表明利福平不影响的生物转化的四氯化碳由P-450 2 E1在体外。因此，利福平对四氯化碳肝毒性的保护作用似乎是由于直接抑制四氯化碳衍生的自由基产生的脂质过氧化作用。
Rifampicin conferred significant protection against carbon tetrachloride (CCl4)-induced liver injury. Serum alanine transaminase (ALT) and aspartate transaminase (AST) activities were not markedly altered and only hepatocellular fatty degeneration was found in mice pretreated with rifampicin (200 mg/kg), whereas severe centrilobular necrosis was observed surd serum ALT and AST activities were as high as 281 and 271 I.U./l, respectively, in the control group following administration of CCl4 (400 mu l/kg). The contents and activities of microsomal drug-metabolizing enzymes in rifampicin-pretreated animals were also much higher than those of the controls. CCl4-mediated. malondialdehyde (MDA) formation was increased in rifampicin-treated liver microsomes, demonstrating that rifampicin was capable of increasing the NADPH-dependent metabolism of CCl4 catalyzed by P-450 2E1 to produce free radicals. However, MDA formation was obviously depressed by rifampicin at varying concentrations from 2 to 32 x 10(-6) M in an in vitro cytochrome P-450 (P-450) enzyme system. On the other hand, NADPH oxidation in the metabolism of CCl4 and aniline hydroxylation were not suppressed in the presence of rifampicin in this systems, suggesting that rifampicin did not influence the biotransformation of CCl4 by P-450 2E1 in vitro. Therefore, the protective effect of rifampicin against CCl4 hepatotoxicity appeared to result from the direct inhibition of lipid peroxidation generated by CCl4-derived free radicals.