Acute Interaction of Halothane and Enflurane with the Metabolism of Ethanol in Isolated Hepatocytes and Liver Cytosol Preparations from the Rat

Abstract

The effects of halothane and enflurane on ethanol (40 mM) oxidation were studied in isolated rat hepatocytes. Anaesthetic (halothane, enflurane and diethyl ether) effect on the activity of alcohol dehydrogenase (ADH) was studied in incubations of cytosol preparations from rat liver. Mean rates of ethanol metabolism ranged from 0.44 to 0.49 μmol ethanol metabolized/mg cell protein/hour in control hepatocytes from fasted and fed animals. These rates were enhanced by 2‐ and 3‐fold in hepatocytes from fed and fasted animals, respectively, when pyruvate (5 mM) was added. Halothane and enflurane both caused dose dependent inhibition of ethanol metabolism (15‐40%) in all hepatocytes without exogenous addition of pyruvate. The inhibitory effect was present also after pyruvate stimulation in hepatocytes from fasted animals, but disappeared in hepatocytes from fed animals when pyruvate was added. The rate of ethanol oxidation by cells from fed rats was enhanced by approximately 40% when the concentration of ethanol was increased from 20 mM to 80 mM. The anaesthetic inhibition of ethanol metabolism was about 20% more pronounced at the higher ethanol concentration compared to the lower concentration when no pyruvate was added. In the presence of pyruvate the effect of anaesthetics was again reversed regardless of ethanol concentration. Halothane (2 mM) and enflurane (2 mM) both caused about 25% inhibition of the ADH‐activity in cytosol preparations while ether (30 mM) caused more than 50% inhibition. No inhibition of hepatocyte uptake of ethanol was caused by any of the three anaesthetics. It was concluded that the volatile anaesthetic agents in addition to their well known membrane effects also seem to be able to interfere directly with the activity of the non‐membrane related enzyme ADH.