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The cytotoxicity of halothane in isolated hepatocytes: Evidence for two different mechanisms
A A van Iersel1, A J de Boer, C W van Holsteijn
1Institute of Veterinary Pharmacology, Pharmacy and Toxicology, University of Utrecht, Bilstraat 172, P.O. Box 80.176, 3508 TD Utrecht, The Netherlands.
Abstract:
The effect of halothane on the functional properties of isolated hepatocytes was investigated. Glycogen levels and the oxygen consumption of hepatocytes, isolated from both control and phenobarbital-induced rats, decreased dose-dependently after exposure to halothane, irrespective of the oxygen concentration of the incubation (5, 12 or 95% oxygen and 5% CO(2)). Halothane did not affect albumin synthesis in hepatocytes, but there was a loss of albumin from cells isolated from control rats, after exposure to the anaesthetic. Hepatocytes from phenobarbital-induced rats, incubated under hypoxic conditions, showed an increased production of ethane and thiobarbituric acid reactants, indicating lipid peroxidation. The cytochrome P-450 contents of the hepatocytes from phenobarbital-induced rats were decreased by halothane. All these effects of halothane were detected without observing any effects on the integrity of the cells, as determined by the leakage of lactate dehydrogenase.
