Enhanced in vivo-lipid peroxidation associated with halothane hepatotoxicity in rats.
To study the role of lipid peroxidation in halothane-induced hepatic damage, ethane exhalation by rats exposed to 1% halothane for 1 hour was determined under normoxic (21% O2) and hypoxic (6% O2) conditions. The effects of microsomal enzyme induction by phenobarbital and/or glutathione depletion on this parameter of in vivo lipid peroxidation were studied. To assess the degree of liver damage, serum activities of liver specific enzymes (glutamate-pyruvate-transaminase, GPT, and sorbitol dehydrogenase, SDH) were measured 3 hrs after the end of exposure. Besides, liver content of thiobarbituric acid-reactive material was estimated as a further parameter of lipid peroxidation. Enhanced rates of lipid peroxidation over basal levels were only seen under conditions leading to hepatic damage, i.e. phenobarbital induction and hypoxia. The highest rate of lipid peroxidation was observed after depletion of hepatic glutathione in addition to microsomal enzyme induction and hypoxia. Deferrioxamine, diethyldithiocarbamate and (+)-catechin inhibited in vivo lipid peroxidation, but only (+)-catechin suppressed halothane-hepatoxicity. These results indicate that halothane-induced hepatic damage is associated with an enhanced rate of lipid peroxidation, but this might not be the only mechanism of halothane toxicity.
Younes
M
M
Institute of Toxicology, School of Medicine, University of Lübeck, FRG.
Heger
B
B
Wilhelm
K P
KP
Siegers
C P
CP
D000818:Animals; D002392:Catechin / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D004050:Ditiocarb / Q000494:pharmacology; D005978:Glutathione / Q000096:biosynthesis / Q000378:metabolism; D006221:Halothane / Q000633:toxicity*; D008054:Lipid Peroxides / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D008054:Lipid Peroxides; D002392:Catechin; D004050:Ditiocarb; D005978:Glutathione; D003676:Deferoxamine; D006221:Halothane; D010634:Phenobarbital