Acute, Sublethal Cyanide Poisoning in Mice Is Ameliorated by Nitrite Alone: Complications Arising from Concomitant Administration of Nitrite and Thiosulfate as an Antidotal Combination

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• 作者：Leah K. Cambal ; Megan R. Swanson ; Quan Yuan ; Andrew C. Weitz ; Hui-Hua Li ; Bruce R. Pitt ; Linda L. Pearce ; Jim Peterson
• 刊名：Chemical Research in Toxicology
• 出版年：2011
• 出版时间：July 18, 2011
• 年：2011
• 卷：24
• 期：7
• 页码：1104-1112
• 全文大小：865K
• 年卷期：v.24,no.7(July 18, 2011)
• ISSN：1520-5010

文摘

Sodium nitrite alone is shown to ameliorate sublethal cyanide toxicity in mice when given from 1 h before until 20 min after the toxic dose as demonstrated by the recovery of righting ability. An optimum dose (12 mg/kg) was determined to significantly relieve cyanide toxicity (5.0 mg/kg) when administered to mice intraperitoneally. Nitrite so administered was shown to rapidly produce NO in the bloodsteam as judged by the dose-dependent appearance of EPR signals attributable to nitrosylhemoglobin and methemoglobin. It is argued that antagonism of cyanide inhibition of cytochrome c oxidase by NO is the crucial antidotal activity rather than the methemoglobin-forming action of nitrite. Concomitant addition of sodium thiosulfate to nitrite-treated blood resulted in the detection of sulfidomethemoblobin by EPR spectroscopy. Sulfide is a product of thiosulfate hydrolysis and, like cyanide, is known to be a potent inhibitor of cytochrome c oxidase, the effects of the two inhibitors being essentially additive under standard assay conditions rather than dominated by either one. The findings afford a plausible explanation for an observed detrimental effect in mice associated with the use of the standard nitrite鈥搕hiosulfate combination therapy at sublethal levels of cyanide intoxication.