TRANSITION-METAL MEDIATED FREE RADICAL FORMATION IN VITRO AND IN VIVO

虽然自由基的形成是已知的发生从库珀在芬顿- 与体外反应一样，尚未检测到铜的自由基 在活体动物中的应用 通过应用ESR和次级自由基 自旋捕获技术，体内羟自由基形成证据 在同时用铜和抗坏血酸处理的大鼠中获得。 羟基自由基的存在也已在文献中得到证实， 硒和维生素E缺乏的大鼠在急性铜条件下 超载。 我们证明了由铜产生的羟基自由基可以 确实在体内发生并导致氧化损伤，尽管在我们 铜中毒大鼠模型中单独铜不能引起 可检测的自由基加合物 百草枯是一种毒素，其毒性归因于其产生 超氧阴离子自由基。 增加超氧化物的产生反过来可以 刺激金属离子在体外和体内形成羟基自由基。 我们已经证明这是真实的铜和铁超载实验 对大鼠 一些金属离子也可能对自由基有有益的影响。 体内代谢物。 我们的研究结果表明，抑制自由基 在大鼠中检测到的肝毒素碳代谢产物 由于用三价铬进行预处理， 自旋捕获实验中人工自由基加合物的形成 是一种必须时刻防范的可能性 我们已经证明 抑制离体金属离子诱导的游离 在金属过载的情况下的自由基化学。 这对于 正确识别体内产生的自由基。 我们建立 在体外抑制人为ESR信号的某些标准 在铜存在下，来自自旋阱DMPO的非自由基化学 和铁离子。

Although free radical formation is known to occur from cooper in Fenton- like reactions in vitro, free radicals from copper have not been detected in living animals until now. By applying ESR and the secondary radical spin trapping technique, evidence for hydroxyl radical formation in vivo was obtained in rats treated simultaneously with copper and ascorbic acid. The existence of hydroxyl radical has also been shown in the file of selenium- and vitamin E-deficient rats during conditions of acute copper overload. We demonstrate that hydroxyl radical generated by copper can indeed occur in vivo and contribute to oxidative damage, though in our model of copper-intoxicated rats copper alone does not cause the formation of detectable radical adducts. Paraquat is a toxin whose toxicity is attributed to its ability to generate the superoxide radical anion. Increased superoxide production can in turn stimulate hydroxyl radical formation in vitro and in vivo from metal ions. We have shown this to be true for both copper and iron overload experiments in rats. Some metal ions may also have beneficial effects on free radical metabolites in vivo. Our results show a suppression of free radical metabolites detected in rats from the metabolism of the hepatotoxin carbon tetrachloride due to pretreatment with trivalent chromium. The formation of artifactual radical adducts in spin trapping experiments is a possibility that must always be guarded against. We have demonstrated experimental procedures necessary to inhibit ex vivo metal ion-induced free radical chemistry in cases of metal overload. This is crucial for correctly identifying radicals generated in vivo. We have established certain criteria for suppressing artifactual ESR signals in vitro resulting from non-radical chemistry of the spin trap DMPO in the presence of copper and iron ions.