US EPA

9964 

Journal Article 

Mechanisms of acute hepatic toxicity: chloroform, halothane, and glutathione 

Brown, BR, Jr; Sipes, IG; Sagalyn, AM 

1974 

1 

Anesthesiology
ISSN: 0003-3022
EISSN: 1528-1175 

41 

6 

554-561 

English 

4433055 

10.1097/00000542-197412000-00005 

WOS:A1974V014700005 

http://://WOS:A1974V014700005
Exit
 

The effects of hepatic microsomal enzyme induction with phenobarbital and depletion of hepatic glutathione (GSH) with diethyl maleate on the acute hepatotoxic responses to chloroform and halothane anesthesia were studied in rats. Phenobarbital pretreatment markedly increased the hepatotoxic response to chloroform anesthesia but had little effect on halothane hepatotoxicity. Hepatic GSH levels were decreased 70-80 per cent by 2 hours of chloroform anesthesia in induced rats hut were unchanged in non-induced rats and in animals anesthetized with halothane. Marked destruction of microsomal electron transfer components was observed in the chlorofonn-anesthetized, induced animals only. Induction caused a large increase in in-vitro covalent binding of CHCl3 metabolites to microsomal protein, which could be prevented by GSH. Diethyl maleate pretreatment lowers GSH content approximately 80 per cent. Chloroform anesthesia produced hepatic necrosis and destruction of microsoma1 enzymes in the absence of induction, but halothane did not. Hepatotoxicity of chloroform appears to he related to two factors: 1) rate of biotransformation; 2) availability of the hepatic antioxidant, GSH. Halothane hepatotoxicity does not proceed by the same sequence of events as does that of chloroform. 

Anesthetics, volatile, halothane; Anesathetics, volatile, chloroform; Biotransformation; enzyme induction; Toxicity, hepatic; Liver, hepatotoxicity