Comparison of efficacies of antidotes to the lethal effects of hydrogen cyanide (HCN) in mice

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• 作者：Hume ; A.S. ; Mozingo ; J. ; Chaney ; L.A.
• 刊名：Toxicology Letters
• 出版年：1998
• 出版时间：July, 1998
• 年：1998
• 卷：95
• 期：Supplement 1
• 页码：84
• 全文大小：112 K

文摘

Most of the research concerned with the development of antidotes to the toxic effects of cyanide has involved pretreatment with a potential antidote followed by the parenteral administration of a cyanide salt. However, most cyanide intoxications involve exposure to HCN by inhalation. Hydroxocobalamin (HOCB), α-ketoglutaric acid (AKG), sodium nitrate (SN), p-aminopropiopherone (PAPP), cobalt edetate (CE) or thiosulfate (S₂O₃) were administered i.p. to JCR mice (20-25 g, n = 10) 15 min. prior to exposure to HCN. An inhalation chamber with the capability of rapid entry and exit of animals was equilibrated at 400 ppm (LCT80) HCN and checked periodically. The administration of HOCB (620 mg/kg), AKG (1000 mg/kg), SN (50 mg/kg), PAPP (2.5 mg/kg) or CE (91 mg/kg) prior to HCN effectively reduced HCN-induced lethality from 80 % to 15, 16, 0, 0 and 0 % , respectively. With the addition of S₂O₃ (500 mg/kg) to either HOCB or AKG, the doses of these agents necessary to decrease lethality from 80 % to 20 % were reduced to 300 and 500 mg/kg, respectively. In separate experiments, groups of mice were exposed first to HCN, removed from the chamber upon display of toxic symptoms, and immediately treated i.p. with AKG (250 mg/kg)/S₂O₃ (500 mg/kg). Lethality was reduced from 73 % to 31 % in these animals. In conclusion, it appears that larger doses of the above antidotes are needed to reduce the LCT80 produced by HCN than are necessary to reduce the LD80 of cyanide salts. The combination of S₂O₃ and HOCB or AKG is significantly greater in antidotal effectiveness than either individual agent alone.