Cronican Andrea A, Frawley Kristin L, Ahmed Humza, Pearce Linda L, Peterson Jim
Department of Environmental and Occupational Health, Graduate School of Public Health, The University of Pittsburgh, 100 Technology Drive, Pittsburgh, Pennsylvania 15219, United States.
Chem Res Toxicol. 2015 Jul 20;28(7):1398-408. doi: 10.1021/acs.chemrestox.5b00015. Epub 2015 Jun 8.
There are currently no FDA-approved antidotes for H2S/sulfide intoxication. Sodium nitrite, if given prophylactically to Swiss Webster mice, was shown to be highly protective against the acute toxic effects of sodium hydrosulfide (∼LD40 dose) with both agents administered by intraperitoneal injections. However, sodium nitrite administered after the toxicant dose did not detectably ameliorate sulfide toxicity in this fast-delivery, single-shot experimental paradigm. Nitrite anion was shown to rapidly produce NO in the bloodstream, as judged by the appearance of EPR signals attributable to nitrosylhemoglobin and methemoglobin, together amounting to less than 5% of the total hemoglobin present. Sulfide-intoxicated mice were neither helped by the supplemental administration of 100% oxygen nor were there any detrimental effects. Compared to cyanide-intoxicated mice, animals surviving sulfide intoxication exhibited very short knockdown times (if any) and full recovery was extremely fast (∼15 min) irrespective of whether sodium nitrite was administered. Behavioral experiments testing the ability of mice to maintain balance on a rotating cylinder showed no motor impairment up to 24 h post sulfide exposure. It is argued that antagonism of sulfide inhibition of cytochrome c oxidase by NO is the crucial antidotal activity of nitrite rather than formation of methemoglobin.
目前尚无美国食品药品监督管理局（FDA）批准的针对硫化氢/硫化物中毒的解毒剂。若对瑞士韦伯斯特小鼠预防性给予亚硝酸钠，腹腔注射两种药物时，亚硝酸钠对氢硫化钠（约LD40剂量）的急性毒性作用具有高度保护作用。然而，在这种快速给药、单次注射的实验模式中，在给予毒物剂量后再给予亚硝酸钠并不能明显改善硫化物毒性。根据归因于亚硝基血红蛋白和高铁血红蛋白的电子顺磁共振信号的出现判断，亚硝酸根阴离子在血液中迅速产生一氧化氮（NO），其总量不到总血红蛋白的5%。给予100%的氧气对硫化物中毒的小鼠既没有帮助，也没有任何有害影响。与氰化物中毒的小鼠相比，硫化物中毒存活的动物击倒时间非常短（如果有），并且无论是否给予亚硝酸钠，完全恢复都非常快（约15分钟）。测试小鼠在旋转圆柱体上保持平衡能力的行为实验表明，在硫化物暴露后24小时内没有运动障碍。有人认为，NO对硫化物抑制细胞色素c氧化酶的拮抗作用是亚硝酸盐关键的解毒活性，而不是高铁血红蛋白的形成。
