Canada A T, Werkman R F, Mansbach C M, Rosen G M
J Free Radic Biol Med. 1986;2(5-6):327-34. doi: 10.1016/s0748-5514(86)80032-0.
In ischemia/reperfusion injury, it is hypothesized that superoxide is responsible for the component of injury due to reperfusion. The superoxide is hypothesized to result from the aerobic oxidation of purines produced by the ischemia-mediated breakdown of high-energy phosphates. This oxidation is catalyzed by xanthine oxidase proposed to be rapidly formed as a result of ischemia-mediated protease conversion from xanthine dehydrogenase. In vivo experiments with the intestine of either rats or guinea pigs were unable to confirm the rapid conversion of xanthine dehydrogenase to xanthine oxidase as a result of ischemia. In vitro experiments with isolated guinea pig enterocytes did show a significant increase in xanthine oxidase activity after these cells were first placed in an anaerobic environment for 60 min and then reoxygenated; however, the magnitude of the increase is such that the biological importance of this finding remains uncertain. Using a variety of techniques, including spin trapping, hydroxylamine oxidation, and vanadate NADPH oxidation, we explored the possibility that superoxide was produced as a result of anoxia followed by reoxygenation in the in vitro enterocyte system. From these experiments, we determined that superoxide is generated as a result of anoxia/reoxygenation. However, from xanthine oxidase inhibition experiments using pterinaldehyde, only a small percentage of the total superoxide produced comes from the action of this enzyme on purines.
在缺血/再灌注损伤中，据推测超氧化物是再灌注所致损伤的组成部分的原因。据推测，超氧化物是由缺血介导的高能磷酸盐分解产生的嘌呤的需氧氧化产生的。这种氧化由黄嘌呤氧化酶催化，该酶被认为是由于缺血介导的蛋白酶将黄嘌呤脱氢酶转化而迅速形成的。对大鼠或豚鼠肠道进行的体内实验无法证实缺血导致黄嘌呤脱氢酶迅速转化为黄嘌呤氧化酶。对分离的豚鼠肠上皮细胞进行的体外实验确实表明，这些细胞首先置于厌氧环境60分钟然后再进行复氧后，黄嘌呤氧化酶活性显著增加；然而，增加的幅度使得这一发现的生物学重要性仍然不确定。我们使用了多种技术，包括自旋捕获、羟胺氧化和钒酸盐NADPH氧化，来探究在体外肠上皮细胞系统中缺氧后再复氧是否会产生超氧化物。从这些实验中，我们确定超氧化物是由缺氧/复氧产生的。然而，使用蝶呤醛进行的黄嘌呤氧化酶抑制实验表明，所产生的总超氧化物中只有一小部分来自该酶对嘌呤的作用。
