黄嘌呤氧化酶抑制剂作为自由基清除剂的作用：别嘌醇和氧嘌呤醇在心肌挽救中的一种新作用机制。

Role of xanthine oxidase inhibitor as free radical scavenger: a novel mechanism of action of allopurinol and oxypurinol in myocardial salvage.

作者信息

Das D K, Engelman R M, Clement R, Otani H, Prasad M R, Rao P S

机构信息

University of Connecticut School of Medicine, Farmington 06032.

出版信息

Biochem Biophys Res Commun. 1987 Oct 14;148(1):314-9. doi: 10.1016/0006-291x(87)91112-0.

DOI:10.1016/0006-291x(87)91112-0

PMID:2823807

Abstract

Xanthine oxidase (XO) has been hypothesized to be a potential source of oxygen-derived free radicals during reperfusion of ischemic myocardium based on the fact that allopurinol, a XO-inhibitor, can reduce reperfusion injury. In this communication we report that both allopurinol and oxypurinol, the principle metabolite of allopurinol, prevent the reperfusion injury in isolated pig heart. However, we found that neither pig heart nor pig blood contain any XO activity. Our study showed a direct free radical scavenging action of these XO-inhibitors during ischemia and reperfusion, as judged by the reduction of free radical signals when compared using an Electron Paramagnetic Resonance Spectrometer. Using a Luminometer, we also confirmed that both allopurinol and oxypurinol can scavenge ClO2, HOCl, and significantly inhibit free radical signals generated by activated neutrophils. These XO-inhibitors, however, failed to scavenge O2. and OH. radicals. Our results suggest that these XO-inhibitors salvaged the ischemic-reperfused myocardium by scavenging free radicals, and not by inhibiting XO in the pig heart.

摘要

基于黄嘌呤氧化酶（XO）抑制剂别嘌呤醇可减轻再灌注损伤这一事实，有人提出假设，认为XO可能是缺血心肌再灌注期间氧衍生自由基的潜在来源。在本报告中，我们指出别嘌呤醇及其主要代谢产物氧嘌呤醇均可预防离体猪心脏的再灌注损伤。然而，我们发现猪心脏和猪血中均不存在任何XO活性。我们的研究表明，通过电子顺磁共振光谱仪比较发现，这些XO抑制剂在缺血和再灌注期间具有直接的自由基清除作用，即自由基信号减少。使用发光计，我们还证实别嘌呤醇和氧嘌呤醇均可清除二氧化氯、次氯酸，并显著抑制活化中性粒细胞产生的自由基信号。然而，这些XO抑制剂无法清除超氧阴离子和羟自由基。我们的结果表明，这些XO抑制剂通过清除自由基而非抑制猪心脏中的XO来挽救缺血再灌注心肌。