Effects of phenobarbital, GSH-depletors, CCl4 and ethanol on the biliary efflux of glutathione in rats.

The efflux of reduced glutathione (GSH) into bile appears to be a major contribution to the hepatic glutathione homeostasis. In bile-fistula rats pretreatment with phenobarbital strongly enhanced the biliary export of GSH, whereas hepatic damage due to carbon tetrachloride markedly decreased the transport of GSH into bile. An oral load of ethanol, which was not hepatotoxic in rats, had the same effect in this respect. Depletion of hepatic GSH in response to the treatment with diethylmaleate, vinylidene chloride or paracetamol was followed by a decrease in the efflux of GSH into bile. Phorone which depleted the hepatic GSH nearly totally, in contrast, even enhanced its biliary output indicating a rapid decomposition of the phorone-GSH-adduct. Our experiments support recent findings of others that the canalicular transport of reduced GSH requires an active energy-dependent carrier mechanism.