Halothane hepatotoxicity and reductive metabolism of halothane in acute experimental liver injury in rats.
Reductive metabolism of halothane was measured after acute liver injury induced by galactosamine (1.0 g/kg, IP) in rats. On the seventh day of liver injury, when previously elevated serum alanine aminotransferase levels had returned to near normal range, anaerobic release of fluoride from halothane by hepatic microsomes, which appears to reflect the reductive pathway of halothane metabolism, was still remarkably decreased (1.36 +/- 0.56 nmol/mg protein/h vs 5.88 +/- 0.58 in controls, P less than 0.001). In another set of experiments, rats (n = 8) given galactosamine 7 days earlier and saline-treated control rats were given halothane anesthesia (1.0%) under mildly hypoxic conditions (F1O2 0.14). In saline controls, halothane anesthesia resulted in a mild but statistically significant increase in serum alanine aminotransferase levels (32 +/- 4 vs 59 +/- 6 U/ml, P less than 0.001). In contrast, serum levels of this enzyme were not changed by halothane anesthesia in galactosamine-treated rats (45 +/- 3 vs 49 +/- 4 U/ml). Although care should be taken in extrapolating the importance of these animal data to humans, the results of this study suggest that halothane hepatotoxicity can be attenuated in the presence of minor liver injury as a result of decreased hepatic biotransformation of the anesthetic. The data support the view that halothane anesthesia is not necessarily contraindicated in subjects with impaired liver function.
Nomura
F
F
Department of Medicine, Chiba University School of Medicine, Japan.
Hatano
H
H
Iida
S
S
Ohnishi
K
K
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D005688:Galactosamine / Q000633:toxicity; D006221:Halothane / Q000378:metabolism / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
D005688:Galactosamine; D003577:Cytochrome P-450 Enzyme System; D000410:Alanine Transaminase; D006221:Halothane