Effects of verapamil on hepatic glutathione in the rat

Effects of verapamil, an calcium channel blocker, on hepatic glutathione were studied in vivo in the rat and in the perfused rat liver. An injection of verapamil at a dose of 15 mg/kg body weight but not at 5 mg/kg significantly decreased hepatic glutathione contents in both fed and fasted animals 6 h after the injection. The administration of verapamil at a dose of 10 mg/kg twice a day for a week brought a significant decrease in hepatic glutathione contents and a significant increase in plasma glutathione levels. In the perfused rat liver, sinusoidal glutathione efflux was significantly increased when verapamil was added to the perfusion medium in a concentration of 20 microM. These data indicate that verapamil increases glutathione efflux from the liver and that calcium mobilization may be concerned in glutathione efflux in vivo.