Comparative toxicity of halothane, isoflurane, hypoxia, and phenobarbital induction in monolayer cultures of rat hepatocytes.
Schieble-TM; Costa-AK; Heffel-DF; Trudell-JR
Anesthesiology 1988 Apr; 68(4):485-494
The comparative toxicities of halothane (151677), isoflurane (26675467), hypoxia and phenobarbital induction for monolayer cultures of rat hepatocytes were determined. Adult male Fisher-344- rats were pretreated with phenobarbital by intraperitoneal injections at 80mg/kg/day for four consecutive days. Hepatocytes were isolated from the livers of both treated and nontreated rats and exposed to 1.5 percent halothane or 2.0 percent isoflurane in 1, 2, or 4 percent oxygen for 2 hours. Immediately after exposure or after 6 hours of incubation, supernatants were analyzed for aspartate-aminotransferase release, and Trypan-Blue exclusion was used to determine cells death. The results obtained immediately and at 6 hours after exposure demonstrated that low oxygen levels, halothane, and phenobarbital pretreatment were each highly significant factors in relation to cell death. A toxic effect of isoflurane was not noted under these conditions. The results of this study clearly indicate that the origin of cell death in hepatocyte monolayers was multifactorial with hypoxia, phenobarbital induction and halothane exposure each contributing to the hepatocyte damage observed in this model.
NIOSH-Publication; NIOSH-Grant; Grants-other; Anesthetics; Laboratory-animals; In-vitro-studies; Liver-cells; Liver-damage; Hepatotoxicity
Anesthesia Stanford University Department of Anesthesia Stanford, Calif 94305
Other Occupational Concerns; Grants-other
Stanford University, Stanford, California