LeBel C P, Bondy S C
Arthur D. Little, Inc., Toxicology Unit, Cambridge, MA 02140.
Neurotoxicol Teratol. 1991 May-Jun;13(3):341-6. doi: 10.1016/0892-0362(91)90081-7.
The inherent biochemical, anatomical and physiological characteristics of the brain make it especially vulnerable to insult. Specifically, some of these characteristics such as myelin and a high energy requirement provide for the introduction of free radical-induced insult. Recently, the biochemistry of free radicals has received considerable attention. It also has become increasingly apparent that many drug and chemical-induced toxicities may be evoked via free radicals and oxidative stress. Major points addressed in this work are the regulation of neural free radical generation by antioxidants and protective enzymes, xenobiotic-induced disruption of cerebral redox status, and specific examples of neurotoxic agent-induced alterations in free radical production as measured by the fluorescent probe dichlorofluorescein. This article considers the thesis that free radical mechanisms may contribute significantly to the properties of several diverse neurotoxic agents and proposes that excess production of free radicals may be common phenomena of neurotoxicity.
大脑固有的生化、解剖和生理特征使其特别容易受到损伤。具体而言,其中一些特征,如髓磷脂和高能量需求,会引发自由基诱导的损伤。近年来,自由基的生物化学受到了相当多的关注。越来越明显的是,许多药物和化学物质诱导的毒性可能是通过自由基和氧化应激引发的。这项工作涉及的要点包括抗氧化剂和保护酶对神经自由基生成的调节、外源性物质引起的大脑氧化还原状态的破坏,以及通过荧光探针二氯荧光素测量的神经毒性剂诱导的自由基产生变化的具体例子。本文认为自由基机制可能在几种不同神经毒性剂的特性中起重要作用,并提出自由基的过量产生可能是神经毒性的常见现象。