Inhibition of Energy Production by Halothane Metabolites

Trifluoroethanol (TFE), trifluoroacetaldehyde hydrate (TFA1H) and trifluoroacetic acid, which are metabolites of halothane and fluroxene, were given intraperitoneally to mice. TFE, in lethal doses of 300 and 600 mg/kg caused a significant decrease of the ATP content and the ATP/ADP ratio in mice livers 17 hrs after the administration. TFE, however, did not decrease the content of creatine phosphate (nor the creatine phosphate/creatine ratio) in mice hearts or muscles. All the three halothane metabolites inhibited anaerobic glycolysis (14–72%) in the liver, the greatest inhibition occuring 17 hrs after the administration of TFA1H. In vitro only TFE and TFA1H were found to be inhibitors. Ethanol, which protects against the toxicity of TFE, did not modify the inhibition of glycolysis in vivo, but totally prevented the decrease in the ATP/ADP ratio. The inhibition of glycolysis as well as the discrepancy between the changes in ATP and creatine phosphate concentrations may be explained by an inhibition by trifluoroacetaldehyde or its derivative of enzymes with active thiol groups.