Effect of phenobarbital and 3-methylcholanthrene treatment on NADPH- and NADH-dependent production of reactive oxygen intermediates by rat liver nuclei.
Effect of phenobarbital and 3-methylcholanthrene treatment on NADPH- and NADH-dependent production of reactive oxygen intermediates by rat liver nuclei.
复制标题
苯巴比妥和 3-甲基胆蒽治疗对大鼠肝核 NADPH 和 NADH 依赖性活性氧中间体产生的影响。
DOI：
10.1016/0304-4165(92)90122-b
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Cederbaum,AI
中科院分区：
文献类型：
--
作者：
Puntarulo,S;Cederbaum,AI
评估了诱导大鼠肝核混合功能氧化酶系统苯巴比妥或 3-甲基胆蒽对 NADPH 和 NADH 依赖性活性氧中间体产生的影响。诱导剂使细胞色素P-450增加2倍，NADPH-细胞色素还原酶活性增加50%至70%，NADH-细胞色素还原酶活性增加20%至30%。与这些增加相关的是NADPH 和NADH 依赖性羟基自由基(·OH) 类物质和H2O2 的产生的相应增加。 ·OH 的产生速率受过氧化氢酶抑制，并且对超氧化物歧化酶部分敏感。药物处理后，类·OH 物质的核产量增加似乎是由于 H2O2 生成相应增加。与H 2 O 2 和·OH的生成相反，苯巴妥或3-甲基胆蒽处理并没有增加通过核生成硫代巴比妥酸反应性物质。氧化还原循环（例如甲萘醌和百草枯）在对照和诱导的细胞核中以相似的程度增加了氧自由基的产生。这些结果表明，苯巴比妥或3-甲基胆蒽对核混合功能氧化酶系统的诱导可以导致在NADPH或NADH存在下活性氧中间体的产生随后增加。
The effect of inducing the rat liver nuclear mixed-functions oxidase system phenobarbital or 3-methylcholanthrene on NADPH- and NADH-dependent production of reactive oxygen intermediates was evaluated. The inducing agents produced a 2-fold increase in cytochromeP-450, a 50 to 70% increase in NADPH-cytochromecreductase activity, and a 20 to 30% increase in NADH-cytochromecreductase activity. Associated with these increases was a corresponding increase in NADPH- and NADH-dependent production of hydroxyl radical (·OH)-like species and of H2O2. Rates of ·OH production were inhibited by catalase and partially sensitive to superioxide dismutase. The increase in nuclear production of ·OH-like species after drug treatment appears to be due a corresponding increase in H2O2generation. In contrast to H2O2and ·OH generation, production of thiobarbituric acid-reactive material by nuclei was not increased by the phenobartial or 3-methylcholanthrene treatment. Redox cycling such as menadione and paraquat increased oxygen radical generation to similar extents in the control and the induced nuclei. These results indicate that induction of the nuclear mixed-function oxidase system by phenobarbital or 3-methylcholanthrene can result isn a subsequent increase in productionn of reactive oxygen intermediates in the presence of either NADPH or NADH.