Comparison of the relative propensities of isoamyl nitrite and sodium nitrite to ameliorate acute cyanide poisoning in mice and a novel antidotal effect arising from anesthetics.
Comparison of the relative propensities of isoamyl nitrite and sodium nitrite to ameliorate acute cyanide poisoning in mice and a novel antidotal effect arising from anesthetics.
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DOI：
10.1021/tx400103k
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发表时间：
2013-05-20
影响因子：
4.1
通讯作者：
Peterson J
中科院分区：
文献类型：
--
作者：
Cambal LK;Weitz AC;Li HH;Zhang Y;Zheng X;Pearce LL;Peterson J
亚硝酸盐异戊酯以前被认为是可接受的吸入氰化物解毒剂，因此研究了这种有机亚硝酸盐与亚硝酸钠的解毒剂效用。为了便于定量比较，将亚硝酸钠和亚异戊酯以等量的剂量腹腔注射给亚致死氰化物中毒小鼠。在亚硝酸盐异戊酯处理的动物中，从敲低状态恢复的权利明显受到损害，这种影响可归因于亚硝酸盐异戊酯水解释放亚硝酸盐阴离子时产生的异戊醇的毒性。随后，吸入亚硝酸钠气雾剂被证明可以改善亚致死氰化物毒性，在中毒剂量后给予小鼠，与只给予有毒物质的对照动物相比，小鼠的翻身能力恢复得更快。因此，这些实验表明，雾化亚硝酸钠有望成为有机亚硝酸盐的更好替代品，作为一种吸入式氰化物解毒剂。由亚硝基血红蛋白和高铁血红蛋白引起的EPR信号的出现决定了吸入亚硝酸钠导致血液中NO的产生。气溶胶输送是在一个未计量的吸入室中进行的，在本研究中，没有尝试优化程序。有人认为，在人体中施用有效的吸入亚硝酸钠水剂量是可能的，尽管仅仅超出了目前个人计量吸入器设计的能力，例如用于哮喘的吸入器。最后，在略大于LD50的NaCN剂量下工作时，偶然发现(i)麻醉比未麻醉的动物显著延长了生存时间，（ii）麻醉下亚硝酸盐阴离子的解毒剂活性完全消失。对这些作用在小鼠和他们的实际后果有关测试假定的氰化物解毒剂的合理解释进行了讨论。
Isoamyl nitrite has previously been considered acceptable as an inhaled cyanide antidote, so the antidotal utility of this organic nitrite compared with sodium nitrite was investigated. To facilitate a quantitative comparison, doses of both sodium nitrite and isoamyl nitrite were given intraperitoneally in equimolar amounts to sub-lethally cyanide-challenged mice. Righting recovery from the knockdown state was clearly compromised in the isoamyl nitrite-treated animals, the effect being attributable to the toxicity of the isoamyl alchol produced during hydrolysis of the isoamyl nitrite to release nitrite anion. Subsequently, inhaled aqueous sodium nitrite aerosol was demonstrated to ameliorate sub-lethal cyanide toxicity, when provided to mice after the toxic dose, by the more rapid recovery of righting ability compared to control animals given only the toxicant. Aerosolized sodium nitrite has thus been shown by these experiments to have promise as a better alternative to organic nitrites for development as an inhaled cyanide antidote. The inhaled sodium nitrite led to production of NO in the bloodstream as determined by the appearance of EPR signals attributable to nitrosylhemoglobin and methemoglobin. The aerosol delivery was performed in an unmetered inhalation chamber and, in this study, no attempt was made to optimize the procedure. It is argued that administration of an effective inhaled aqueous sodium nitrite dose in humans is possible, though just beyond the capability of current individual metered-dose inhaler designs, such as those used for asthma. Finally, working at slightly greater than LD50 NaCN doses, it was fortuitously discovered that (i) anesthesia leads to significantly prolonged survival compared to unanesthetized animals and (ii) the antidotal activity of nitrite anion was completely abolished under anesthesia. Plausible explanations for these effects in mice and their practical consequences in relation to testing putative cyanide antidotes are discussed.
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影响因子：
2.9
作者：
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通讯作者：
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作者：
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