Document Detail


Cyanide-induced injury to the isolated perfused rat liver.
MedLine Citation:
PMID:  3237595     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
M Younes; O Strubelt
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Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article    
Journal Detail:
Title:  Pharmacology & toxicology     Volume:  63     ISSN:  0901-9928     ISO Abbreviation:  Pharmacol. Toxicol.     Publication Date:  1988 Nov 
Date Detail:
Created Date:  1989-05-02     Completed Date:  1989-05-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8702180     Medline TA:  Pharmacol Toxicol     Country:  DENMARK    
Other Details:
Languages:  eng     Pagination:  382-5     Citation Subset:  IM    
Affiliation:
Institute of Toxicology, Medical University of Lübeck, FRG.
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MeSH Terms
Descriptor/Qualifier:
Animals
Calcium / metabolism
Cyanides / toxicity*
Glutathione / metabolism
Lactates / metabolism
Liver / drug effects*,  metabolism
Oxygen Consumption
Perfusion
Potassium Cyanide / toxicity*
Pyruvates / metabolism
Rats
Rats, Inbred Strains
Chemical
Reg. No./Substance:
0/Cyanides; 0/Lactates; 0/Pyruvates; 151-50-8/Potassium Cyanide; 70-18-8/Glutathione; 7440-70-2/Calcium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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