title: Cerebral cytochrome a,a3 inhibition by cyanide in bloodless rats.
abstract: Brain cytochrome a,a3 inhibition is presumed to be the site of lethal histotoxic hypoxia in cyanide poisoning perhaps because of the relative inability of the brain to metabolize cyanide. However, only limited data are available about cyanide toxic effects and possible antagonism in the in vivo brain. In this study, in situ, multiple wavelength, spectrophotometric monitoring of brain cytochrome a,a3 was used to observe oxidation-reduction (redox) responses of cerebral cytochrome a,a3 to intravenous potassium cyanide administration. Bloodless rats prepared by perfluorochemical emulsion (FC-43) exchange transfusion allowed monitoring of cyanide-cytochrome a,a3 interaction without spectral interference by hemoglobin. We found that cyanide-induced transient increases in cytochrome a,a3 reduction level and subsequent redox recovery kinetics were similar in bloodless and normal blood circulated rats. Electroencephalographic activity was maintained until a 50% increase in the reduction level of cytochrome a,a3 was induced with cyanide. Pre-treatment with the cyanide antagonist sodium thiosulfate also protected brain cytochrome a,a3 from cyanide-mediated redox state changes by approximately 4-fold both in normal blood circulated controls and during FC-43 circulation. These latter results indicate that sodium thiosulfate, presumably acting at tissue sites of rhodanese activity, can prevent cerebral cytochrome a,a3 reduction by cyanide even in the virtual absence of blood or circulating proteins.
mesh_terms: D000818:Animals; D001790:Blood Physiological Phenomena; D001921:Brain / Q000201:enzymology*; D002248:Carbon Monoxide / Q000494:pharmacology; D003486:Cyanides / Q000633:toxicity*; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors*; D005078:Exchange Transfusion, Whole Blood; D005466:Fluorocarbons / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013053:Spectrophotometry; D013885:Thiosulfates / Q000494:pharmacology
chemical_list: D003486:Cyanides; D005466:Fluorocarbons; D013885:Thiosulfates; D002248:Carbon Monoxide; D003576:Electron Transport Complex IV; C017717:sodium thiosulfate