HYPEROXIA AND GLUTATHIONE DEPLETION IN THE ISOLATED-PERFUSED RAT-LIVER

Background: Hepatic stores of glutathione may be depleted by hyperoxic exposure or poor nutritional status, We studied the effects of hypero xia or hepatic glutathione depletion on bile flow rates, and on biliar y concentrations of glutathione and amino acids. Methods: Glutathione depletion was induced in vivo by 1) hyperoxic exposure (O-2) for 48 ho urs, 2) inhibition of glutathione synthesis by treatment with buthioni ne sulfoximine (BSO), 3) a combination of BSO + O-2, or 4) inhibition of cysteine synthesis by propargylglycine (PPG), Livers were then isol ated and perfused. Results: Glutathione concentrations in bile, liver, and perfusate were significantly decreased by all treatments, Bile fl ow. was significantly decreased in groups treated with BSO or O-2 + BS O, and perfusate LDH was increased by O-2 + BSO or PPG. Significant ch anges in biliary amino acid concentrations included decreased sulfur-c ontaining amino acids and increased branched-chain amino acids in grou ps treated with BSO, PPG, or O-2; and increased essential amino acids in groups treated with O-2 or PPG. Conclusion: Oxygen exposure or inhi bition of glutathione synthesis results in significant decreases in he patic, perfusate and biliary glutathione concentrations, and increases in biliary amino acids, A decrease in bile flow rate was: associated only with the most severe glutathione depletion.