Document Detail


Halothane hepatotoxicity in hyperthyroid rats as compared to the phenobarbital-hypoxia model.
MedLine Citation:
PMID:  6868087     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Halothane hepatotoxicity was observed after exposing hyperthyroid rats to 0.625% halothane for 4 hr under hypoxic conditions (10% O2). In this model, increases in serum enzyme activities of the alanine aminotransferase (GPT) and the sorbitol dehydrogenase (SDH) were evident immediately following exposure and were six-fold higher than in the phenobarbital-hypoxic model. Plasma free-fluoride levels estimated immediately after exposure to halothane were increased twofold in halothane-exposed hyperthyroid rats under hypoxic conditions as were increased twofold in halothane-exposed hyperthyroid rats under hypoxic conditions as compared to a sixfold increase in the phenobarbital-hypoxic model. The concentration of glutathione in liver was more markedly decreased in hyperthyroid rats than in phenobarbital-induced rats. The fact that no clear-cut correlation was found between defluorination and hepatotoxicity in both models may favor the hypothesis that a non-defluorinated metabolite of halothane, e.g., 2-chloro-1,1,1-trifluoroethyl radical, is the reactive intermediate responsible for the liver lesions. On the other hand, intracellular hypoxia due to hypermetabolism during the hyperthyroid state may be the reason for the higher sensitivity of hyperthyroid rats.
Authors:
C P Siegers; A Frühling; M Younes
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Toxicology and applied pharmacology     Volume:  69     ISSN:  0041-008X     ISO Abbreviation:  Toxicol. Appl. Pharmacol.     Publication Date:  1983 Jun 
Date Detail:
Created Date:  1983-08-26     Completed Date:  1983-08-26     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0416575     Medline TA:  Toxicol Appl Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  257-64     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Anoxia / complications*,  metabolism
Drug-Induced Liver Injury / etiology*
Fluorides / blood
Glutathione / metabolism
Halothane / metabolism,  toxicity*
Hyperthyroidism / complications*,  metabolism
Liver / metabolism
Male
Oxidation-Reduction
Phenobarbital / toxicity*
Rats
Rats, Inbred Strains
Chemical
Reg. No./Substance:
0/Fluorides; 151-67-7/Halothane; 50-06-6/Phenobarbital; 70-18-8/Glutathione

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


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