RADICAL ANION METABOLITES

自由基阴离子代谢物

• 批准号: 3965263
• 负责人: R P MASON
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3965263
• 关键词: NAD(H) phosphate; NADPH cytochrome c2 reductase; anions; biotransformation; chemical substitution; cytochrome P450; electron spin resonance spectroscopy; free radicals; halocarbon compound; liver; local antiinfective agents; microsomes; mitochondria; nicotinamide adenine dinucleotide; nitro compounds; nitrobenzene; toxin metabolism

The objective of this study is to determine the role played by free radicals in the reductive metabolism of xenobiotics. The anaerobic incubation of almost all nitroaromatic xenobiotics, e.g., nitrobenzene, by the microsomal, mitochondrial, or cytosolic fractions of rat liver in the presence of either NADH or NADPH, leads to a multiple-line electron spin resonance spectrum characteristic of the nitro anion free radical. We have now demonstrated nitro anion radical formation by mitochondria using endogenous cofactors. Nitro drugs do not affect mitochondrial respiration, in particular the coupling to ADP. The sites of nitro reduction, as determined by inhibitors of the mitochondrial transport chain, appear to be NADH dehydrogenase and outer-membrane NAD(P)H cytochrome c reductase. Halogen-substituted nitro compounds are radiosensitizers and are among the most toxic nitro compounds. Loss of halide by the nitroaromatic anion forms a very reactive carbon-centered free radical, detected by spin trapping, which reacts with cellular macromolecules. The irreversible binding of these nitro compounds to DNA, protein, etc. may be inhibited by spin traps. Free radical formation by hepatic microsomal cytochrome P-450 reduction of gentian violet, SO2, CCl4 and O2 has also been investigated.

这项研究的目的是确定自由发挥的作用， 自由基在异生物质的还原代谢。 厌氧 培养几乎所有的硝基芳香族异生物质，例如，硝基苯，通过 大鼠肝脏的微粒体、线粒体或胞质组分， NADH或NADPH的存在，导致多线电子自旋 硝基阴离子自由基的共振光谱特征。 我们有 现在证明了硝基阴离子自由基的形成线粒体使用 内源性辅因子 硝基药物不影响线粒体呼吸， 特别是与ADP的偶联。 硝基还原的位点，如 由线粒体转运链的抑制剂决定，似乎是 NADH脱氢酶和外膜NAD（P）H细胞色素c还原酶。 卤素取代的硝基化合物是放射增敏剂， 最毒的硝基化合物 硝基芳族阴离子导致的卤化物损失 形成一个非常活跃的碳中心自由基，通过自旋检测 捕获，与细胞大分子反应。 不可逆 这些硝基化合物与DNA、蛋白质等的结合可以被以下物质抑制 自旋陷阱 肝微粒体细胞色素P-450还原产生自由基 研究了龙胆紫、SO_2、CCl_4和O_2等对植物生长的影响。