Effect of halothane on hypoxic toxicity and glutathione status in cultured rat hepatocytes.
Anesthesiology
; 79(5): 1061-71, 1993 Nov.
Article
em En
| MEDLINE
| ID: mdl-8238983
ABSTRACT
BACKGROUND:
In hypoxic rats, halothane causes hepatotoxicity at oxygen levels that would cause minimal hepatotoxicity in the absence of halothane. Using a model that excludes systemic and extrahepatic effects of halothane, the authors tested the hypothesis that halothane hepatotoxicity in the whole-rat model is caused by a direct hepatotoxic effect of halothane, which is mediated by halothane-derived free radicals.METHODS:
Rat hepatocyte monolayer cultures were exposed to defined gas phases for 2 h. Three experimental variables were present or absent hypoxia (1% O2), halothane (2%), and cytochrome P-450 induction (by phenobarbital). Two experimental outcomes were measured aspartate aminotransferase release, a measure of cell death, and reduced glutathione, an endogenous free radical scavenger whose levels are decreased by physiologically significant free radical injury.RESULTS:
As anticipated, hypoxia increased cell death. Cytochrome P-450 induction by itself increased cell death during hypoxia. However, halothane had no effect on cell death during hypoxia, with or without cytochrome P-450 induction. Halothane had no toxic effect, even when glutathione was depleted before the onset of hypoxia. Glutathione was decreased moderately by hypoxia alone. Neither halothane nor cytochrome P-450 induction had any effect on glutathione levels.CONCLUSIONS:
Halothane was not toxic, and it did not generate a physiologically significant free radical insult during hypoxia in the isolated rat hepatocyte under the experimental conditions used in testing.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hipóxia Celular
/
Glutationa
/
Halotano
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
1993
Tipo de documento:
Article