Halothane induced hepatic necrosis in rats: the role of in vivo lipid peroxidation.
Hepatic damage was induced in phenobarbitone pretreated male Fischer 344 rats by the administration of 1% halothane in 14% oxygen for either 1 or 2 hours. Ethane production during the exposure period was not significantly different between the halothane and non-halothane exposed groups. Animals were sacrificed 1, 2, 6 and 24 hrs from commencement of anaesthesia and the hepatic microsomal fraction analyzed for diene conjugates, lipid hydroperoxides, total lipid content and fatty acid composition. Animals exposed to halothane and sacrificed at 2 and 24 hrs had significantly elevated levels of diene conjugates (P less than 0.05), while lipid hydroperoxide concentration and serum alanine aminotransferase increased in only those animals sacrificed at 24 hrs. Alterations in total lipid content and hepatic microsomal fatty acid composition were not observed in animals sacrificed after 1 and 2 hrs. A significant reduction in total lipid and arachidonic acid content occurred only in those animals sacrificed 24 hrs after exposure, however a concomitant increase in the saturated fatty acid fraction was not observed. It is proposed that alterations in fatty acid composition in vivo and evidence of lipid peroxidation occur as a result of cell death rather than an initiating event in halothane induced hepatic necrosis in rats.
Knights
K M
KM
Department of Anaesthesia and Intensive Care, Flinders University of South Australia, Bedford Park.
Gourlay
G K
GK
Gibson
R A
RA
Cousins
M J
MJ
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D005227:Fatty Acids / Q000378:metabolism; D006221:Halothane / Q000633:toxicity*; D050356:Lipid Metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009336:Necrosis / Q000139:chemically induced*; D010634:Phenobarbital / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344
D005227:Fatty Acids; D000410:Alanine Transaminase; D006221:Halothane; D010634:Phenobarbital