Jurima-Romet M, Huang H S, Paul C J, Thomas B H
Biochemical Toxicology Section, Drug Toxicology Division, Health and Welfare, Canada, Ottawa.
Toxicol Lett. 1991 Nov;58(3):257-67. doi: 10.1016/0378-4274(91)90037-7.
Enalapril maleate (EN) incubated with primary cultures of rat hepatocytes was cytotoxic in concentrations of 0.5 mM or greater. Toxicity was measured by release of lactate dehydrogenase (LDH) into the culture medium at 24 h. SKF525A, alpha-naphthoflavone (alpha NF) and metyrapone (MTP) reduced the toxicity of EN. In vivo pretreatment with phenobarbital (PB) and beta-naphthoflavone (beta NF) had minor protective effects on the responses of hepatocytes to EN exposure. However, in vivo pretreatment with pregnenolone-16 alpha-carbonitrile (PCN) substantially potentiated EN cytotoxicity. These results suggest that the cytocidal hepatotoxicity of EN in primary culture depends to some degree on metabolic activation by a cytochrome P450 species.
与原代培养的大鼠肝细胞一起孵育的马来酸依那普利（EN），在浓度为0.5 mM或更高时具有细胞毒性。通过在24小时时向培养基中释放乳酸脱氢酶（LDH）来测定毒性。SKF525A、α-萘黄酮（αNF）和甲吡酮（MTP）降低了EN的毒性。用苯巴比妥（PB）和β-萘黄酮（βNF）进行体内预处理，对肝细胞对EN暴露的反应具有轻微的保护作用。然而，用孕烯醇酮-16α-腈（PCN）进行体内预处理会显著增强EN的细胞毒性。这些结果表明，EN在原代培养中的细胞毒性肝毒性在一定程度上取决于细胞色素P450种类的代谢激活。
