Smith R P, Wilcox D E
Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH 03755-3835.
Crit Rev Toxicol. 1994;24(4):355-77. doi: 10.3109/10408449409017923.
Nitric oxide (NO) has been discovered recently to be a ubiquitous, endogenous mediator, which is responsible for a variety of normal physiological functions. However, NO also has been implicated in several pathophysiological processes. For example, the pulmonary toxicity of various nitrogen oxides, including NO, found in photochemical smog has been studied for decades; endogenous NO also is associated with bleomycin-induced lung damage, as well as other adverse effects. Recently, a variety of xenobiotics have been shown to owe their biological activity in vivo to their biotransformation to NO. Thus, the therapeutic vasodilatation produced by drugs such as nitroglycerin and sodium nitroprusside is now believed to result from their release of NO, which then mimics the effects of endogenously synthesized NO. The toxic effects of NO prodrugs are, therefore, a matter of concern, especially the extent to which, if any, NO contributes to their toxicity. As reviewed here, NO does not appear to contribute importantly to the toxicity of the NO donors nitrite, hydroxylamine, or nitroprusside. However, it is by no means clear whether or not the NO generated in vivo from sodium azide contributes in a major way to its toxicity. Azide is almost as acutely toxic as cyanide, with which it shares a number of biological effects; yet, azide also has certain cardiovascular actions in common with nitrite. Unlike either cyanide or nitrite, some evidence suggests a tendency for azide to produce low-grade cumulative toxicity. In laboratory animals, azide frequently produces nonasphyxial convulsions, whereas most human deaths appear to be the result of cardiovascular collapse. Neither of these azide-induced syndromes appears to be due to the inhibition of cytochrome c oxidase. Azide is widely used as a preservative in aqueous laboratory reagents and as the propellant in automobile air bags and aircraft escape chutes. Both of these inflable systems are generally safe, and will prevent untold numbers of injuries and deaths. However, to protect workers who handle these devices and others who may come into contact with the sodium azide propellant in these systems, our rudimentary knowledge of azide toxicity needs to be expanded.
一氧化氮（NO）最近被发现是一种普遍存在的内源性介质，它负责多种正常生理功能。然而，NO也与多种病理生理过程有关。例如，光化学烟雾中发现的包括NO在内的各种氮氧化物的肺毒性已经研究了数十年；内源性NO也与博来霉素诱导的肺损伤以及其他不良反应有关。最近，多种外源性物质已被证明其体内的生物活性归因于它们生物转化为NO。因此，现在认为硝酸甘油和硝普钠等药物产生的治疗性血管舒张是由于它们释放NO，然后NO模拟内源性合成NO的作用。因此，NO前药的毒性作用值得关注，尤其是NO在多大程度上（如果有的话）对其毒性有贡献。如下所述，NO似乎对亚硝酸盐、羟胺或硝普钠等NO供体的毒性没有重要贡献。然而，叠氮化钠在体内产生的NO是否对其毒性有主要贡献，这一点绝不清楚。叠氮化钠的急性毒性几乎与氰化物一样，它们有许多共同的生物学效应；然而，叠氮化钠也与亚硝酸盐有某些共同的心血管作用。与氰化物或亚硝酸盐不同，一些证据表明叠氮化钠有产生低度累积毒性的倾向。在实验动物中，叠氮化钠经常引起非窒息性惊厥，而大多数人类死亡似乎是心血管衰竭的结果。这两种由叠氮化钠引起的综合征似乎都不是由于细胞色素c氧化酶的抑制。叠氮化钠被广泛用作实验室水性试剂的防腐剂以及汽车安全气囊和飞机逃生滑梯的推进剂。这两种充气系统通常都是安全的，将防止无数的伤害和死亡。然而，为了保护处理这些装置的工人以及可能接触这些系统中叠氮化钠推进剂的其他人，我们对叠氮化钠毒性的初步了解需要扩展。
