Cyanide-induced injury to the isolated perfused rat liver.
In order to study the events that follow cyanide-induced inhibition of oxidative metabolism and produce cellular injury, isolated, haemoglobin-free perfused rat livers from fasted rats were exposed to KCN (100 mg/l). KCN reduced the oxygen consumption of the livers by about 80%. Hepatotoxicity was evident by a marked release of enzymes (LDH, SDH) and of glutathione (mainly GSSG) into the perfusate, by a depletion of hepatic glutathione and by an accumulation of calcium in the liver. Cyanide-induced hepatotoxicity could be prevented completely by feeding the rats before preparing the liver as well as by addition of fructose to the perfusate of fasted livers. Both treatments resulted in an increased energy supply from anaerobic glycolysis as evidenced by a large release of lactate + pyruvate into the perfusate. The toxic actions of cyanide were markedly attenuated by deferrioxamine as well as by allopurinol. These antitoxic actions occurred without changes in anaerobic glycolysis. Omission of calcium from the perfusate, however, did not influence cyanide toxicity. Thus, energy supply from anaerobic glycolysis seems to be sufficient for the basic functions of the liver to occur, when oxidative metabolism is inhibited by cyanide. The effects of deferrioxamine and allopurinol indicate the involvement of radical intermediates and/or Fe2+ in cyanide-induced cellular toxicity. An influx of calcium from the extracellular to the intracellular space is not involved in cyanide-induced hepatocellular injury.
Younes
M
M
Institute of Toxicology, Medical University of Lübeck, FRG.
Strubelt
O
O
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003486:Cyanides / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption; D010477:Perfusion; D011190:Potassium Cyanide / Q000633:toxicity*; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D003486:Cyanides; D007773:Lactates; D011773:Pyruvates; D005978:Glutathione; D011190:Potassium Cyanide; D002118:Calcium