Free radicals as mediators of alcohol toxicity.
Free radicals as mediators of alcohol toxicity.
复制标题
DOI：
--
复制
发表时间：
1999-11
期刊：
影响因子：
--
通讯作者：
D. Mantle;V. Preedy
中科院分区：
文献类型：
--
作者：
D. Mantle;V. Preedy
在这篇文章中，我们回顾了最近的证据支持的假设，急性/慢性酒精毒性介导的主要是通过在各种组织中产生破坏性的自由基物种。在人体、动物模型或体外实验系统中的研究表明：（1）通过esr光谱分析直接证实了乙醇诱导的自由基种类;（2）组织中乙醇诱导的自由基损伤的间接标志物增加，如脂质过氧化物和蛋白质羰基;（3）乙醇诱导的内源性组织抗氧化剂水平的改变。这些数据表明乙醇诱导自由基是一个复杂的相互作用过程。乙醇代谢的经典途径，由乙醇脱氢酶催化形成乙醛，导致自由基的形成，这是由NADH水平和NADH/NAD+氧化还原比的伴随变化引起的，这反过来又调节自由基产生酶黄嘌呤氧化酶的活性。在微粒体中诱导β 2 E1导致HER的产生，HER是乙醇诱导自由基形成的另一条主要途径。除上述之外，乙醇还可以通过醛氧化酶与乙醛或NADH的反应诱导自由基形成，以通过促氧化剂铁的代谢中的干扰产生氧自由基，或通过在线粒体氧化代谢改变后增加从线粒体的流出。
In this article we have reviewed recent evidence in support of the hypothesis that acute/chronic alcohol toxicity is mediated primarily via the generation of damaging free radical species in various tissues. Studies in man, animal model or in vitro experimental systems have shown: (1) the demonstration of alcohol-induced free radical species directly via esr spectroscopic analysis; (2) increases in indirect markers of ethanol-induced free radical damage in tissues, such as lipid peroxides and protein carbonyl; (3) ethanol-induced alterations in the levels of endogenous tissue antioxidants. These data show the induction of free radicals by ethanol to be a complex interactive process. The classical pathway for ethanol metabolism, catalysed by alcohol dehydrogenase to form acetaldehyde, results in the formation of free radicals, resulting from concomitant changes in NADH levels and NADH/NAD+ redox ratios, which in turn modulate the activity of the free radical generating enzyme xanthine oxidase. The induction of CYP 2E1 in the microsomes results in the generation of HER, another major route by which ethanol induces free radical formation. In addition to the above, ethanol may also induce free radical formation via the reaction of aldehyde oxidase with acetaldehyde or NADH to generate oxyradicals via disturbance in the metabolism of the pro-oxidant iron, or via increased efflux from mitochondria following altered mitochondrial oxidative metabolism.