CONTRIBUTION OF HEPATIC CYTOCHROME-P450 SYSTEMS TO THE GENERATION OF REACTIVE OXYGEN SPECIES
CONTRIBUTION OF HEPATIC CYTOCHROME-P450 SYSTEMS TO THE GENERATION OF REACTIVE OXYGEN SPECIES
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DOI：
10.1016/0006-2952(94)90235-6
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发表时间：
1994-07-05
影响因子：
5.8
通讯作者：
NADERI, S
中科院分区：
文献类型：
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作者：
BONDY, SC;NADERI, S
用荧光探针检测肝微粒体中活性氧（ROS）的生成速率。这个速率以与NADPH浓度成正比的方式被刺激。NADH不能取代NADPH，混合功能氧化酶抑制剂（SKF 525A）阻断了NADPH的刺激。这表明细胞色素P450氧化酶系统参与ROS的形成。低分子量的铁盐可能没有参与刺激的ROS形成，因为去铁胺未能消除对NADPH的氧化反应。过氧化氢酶仅部分抑制，而谷胱甘肽过氧化物酶没有明显抑制这种反应，这意味着过氧化氢不起关键作用。然而。由于nadph增强的活性氧的生成完全被超氧化物歧化酶阻止，所以超氧化物是一个必须的中间体。甲苯、乙醇或苯巴比妥的存在并没有促进nadph影响的活性氧的产生；在没有底物的情况下，受细胞色素P450酶氧化的自由基产生最大。肝细胞色素P450氧化酶可能对整体ROS形成有显著贡献，即使在没有诱导混合功能氧化酶的基础条件下也是如此。
The rate of generation of reactive oxygen species (ROS) in hepatic microsomes was assayed using a fluorescent probe. This rate was stimulated in a manner proportional to the concentration of NADPH present. NADH could not be substituted for NADPH, and an inhibitor of mixed-function oxidases (SKF 525A) blocked stimulation by NADPH. This suggested the involvement of cytochrome P450 oxidase systems in ROS formation. Low molecular weight iron salts may not have been involved in the stimulated ROS formation since deferoxamine failed to eliminate the oxidative response to NADPH. Catalase only partially inhibited, and glutathione peroxidase did not significantly inhibit this response, implying that hydrogen peroxide does not play a key role. However. since NADPH-enhanced generation of reactive oxygen species was totally prevented by superoxide dismutase, superoxide was an obligatory intermediate. The presence of toluene, ethanol or phenobarbital did not enhance the production of NADPH-effected reactive oxygen species; free radical production was maximal in the absence of substrates subject to oxidation by cytochrome P450 enzymes. Hepatic cytochrome P450 oxidases are likely to contribute significantly to overall ROS formation, even under basal conditions where mixed-function oxidases are not induced.