Acute Effects of Halothane and Enflurane on Drug Metabolism and Protein Synthesis in Isolated Rat Hepatocytes

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Abstract
The metabolism of sulfanilamide, antipyrine and paracetamol was studied in the absence and presence of the anesthetics halothane and enflurane at 3 different concentrations (0.5, 1.0 and 2.0 mM) in isolated hepatocytes from the rat. Cell viability and protein synthesis was monitored to evaluate toxic effects. A strong concentration related inhibition of antipyrine oxidation (40-70%) and paracetamol conjugation (20-40%) was caused by both halothane and enflurane. Acetylation of sulfanilamide was not inhibited, as a slight augmentation was noticed. A significant dose related decrease of cell viability (3-13%) was caused by both anesthetics. Dose dependent inhibition of the synthesis of stationary cell proteins (15-60%) and the synthesis/secretion of medium proteins (35-85%) was caused by halothane. Similar but slightly less pronounced effects were caused by enflurane. Volatile anesthetics may have general effects as well as different degrees of specific effects on both membrane-bound enzyme and soluble enzyme activities.