Boutin J A, Kass G E, Moldéus P
Department of Toxicology, Karolinska Institutet, Stockholm, Sweden.
Toxicology. 1989 Feb;54(2):129-37. doi: 10.1016/0300-483x(89)90039-5.
A method for measuring drug-induced hydrogen peroxide production in freshly isolated rat hepatocytes is described. 3-Amino-1,2,4-triazole, an irreversible inhibitor of the enzyme catalase markedly reduces the capacity of isolated hepatocytes to metabolize hydrogen peroxide, with maximum inhibition (80%) being observed after 40 min of co-incubation. The present method is based on the observation that this inhibition of catalase by 3-amino-1,2,4-triazole is prevented by methanol and that the effect of methanol is reversed in the presence of hydrogen peroxide. Using this assay we could demonstrate increased hydrogen peroxide production during the metabolism of diquat, paraquat, xanthine, benzylamine and glycolate by hepatocytes. Inhibition of the hydrogen peroxide metabolic capacity was greatest with glycolate and diquat, whereas paraquat and benzylamine only had a minor effect.
本文描述了一种测量新鲜分离的大鼠肝细胞中药物诱导的过氧化氢生成量的方法。3-氨基-1,2,4-三唑是过氧化氢酶的不可逆抑制剂，它能显著降低分离肝细胞代谢过氧化氢的能力，共孵育40分钟后可观察到最大抑制率（80%）。本方法基于以下观察结果：甲醇可防止3-氨基-1,2,4-三唑对过氧化氢酶的这种抑制作用，且在过氧化氢存在的情况下，甲醇的作用会逆转。利用该测定法，我们可以证明肝细胞在代谢百草枯、敌草快、黄嘌呤、苄胺和乙醇酸的过程中过氧化氢生成量增加。乙醇酸和百草枯对过氧化氢代谢能力的抑制作用最大，而敌草快和苄胺的影响较小。
