Liver damage does not increase the sensitivity of mice to cyanide given acutely.
The major detoxification pathway for cyanide (CN) in many species is a biotransformation to the less toxic thiocyanate (SCN). Hepatic thiosulfate: cyanide sulfurtransferase (rhodanese) is the principal enzyme demonstrating in vitro catalytic activity. Despite the assumed importance of the hepatic enzyme for CN detoxification in vivo, the effects of liver damage (surgical or chemical) on cyanide lethality in animals have not been examined previously. Male CD-1 mice were pretreated with carbon tetrachloride (CCl4, 1 ml/kg, i.p.) 24 h prior to the administration of sodium cyanide (NaCN). In other experiments CCl4 was given in the same doses at both 48 h and 24 h prior to NaCN. Hepatotoxicity was documented by elevated serum glutamicpyruvic transaminase (SGPT) activity, by histologic evaluation of the extent of cellular necrosis, by electron microscopy of the mitochondrial fraction, and by the increased duration of zoxazolamine-induced paralysis. Lethality was not changed by CCl4 pretreatments when NaCN was given alone in doses of 4 or 6 mg/kg or at a dose of 10.7 mg/kg following sodium thiosulfate (Na2S203, 1 g/kg, i.p.). A small but statistically significant protective effect was exhibited by CCl4 when NaCN was given at a dose of 16 mg/kg following the administration of Na2S203. Rhodanese activity as measured in mitochondrial preparations fractionated from the livers of mice pretreated with CCl4 was not different from that in animals given the corn oil vehicle even though electron micrographs showed extensive mitochondrial damage. No difference in CN lethality was evident between sham-operated mice and partially (2/3) hepatectomized mice at 24 h post-surgery. An intact healthy liver does not appear to be essential for cyanide detoxification in mice whether or not thiosulfate is also given. Because rhodanese activity was slightly but significantly higher in mitochondria lysed by Triton X-100 than in intact mitochondria, the mitochondrial membrane may constitute a barrier to Na2S203.
D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride / Q000494:pharmacology / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury; D003486:Cyanides / Q000633:toxicity*; D008658:Inactivation, Metabolic; D007274:Injections, Intraperitoneal; D008107:Liver Diseases / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D012966:Sodium Cyanide / Q000633:toxicity*; D013884:Thiosulfate Sulfurtransferase / Q000378:metabolism; D013885:Thiosulfates / Q000494:pharmacology
D003486:Cyanides; D013885:Thiosulfates; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D013884:Thiosulfate Sulfurtransferase; C017717:sodium thiosulfate; D012966:Sodium Cyanide