Antagonism of Acute Sulfide Poisoning in Mice by Nitrite Anion without Methemoglobinemia

作者:Cronican Andrea A; Frawley Kristin L; Ahmed Humza; Pearce Linda L*; Peterson Jim
来源:Chemical Research in Toxicology, 2015, 28(7): 1398-1408.
DOI:10.1021/acs.chemrestox.5b00015

摘要

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 (similar to LD40,dose) with both agents administered by intraperitoneal injections. However, sodium nitrite administered after the toidcant dose did not defectably 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 (similar to 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.

  • 出版日期2015-7