THE ROLE OF GLUTATHIONE IN BILE SECRETION OF ENDOGENOUS TRACE-ELEMENTS IN RATS

To evaluate the role of glutathione in biliary secretion of endogenous trace elements, we quantitated trace element output rates by proton-i nduced x-ray emission under various conditions with altered biliary gl utathione secretion and hepatic glutathione content in the rat. Treatm ent with phenobarbital (80 mg/kg body weight, 4 days), ethanol (0.9 gm /kg body weight, 4 days), or diethylmaleate (3.9 mmol/kg body weight) resulted in changes in biliary glutathione secretion of +114%, -56%, a nd -95%, respectively, and in hepatic glutathione content of -0%, +25% , and -86%, respectively, when compared with control values. Biliary g lutathione level was below detection limits in mutant Groningen Yellow Wistar rats, whereas hepatic glutathione content was increased by 114 % in these animals. Glutathione secretion showed a linear relationship with bile flow when data from all experiments were included in the an alysis; the apparent choleretic activity of glutathione was 67 mul/mum ol. Six trace elements (iron, zinc, copper, manganese, molybdenum, bro mine) could always be detected in bile. Potassium and calcium were mea sured for comparative purposes. No relation was found between biliary trace element secretion and hepatic glutathione content. Biliary outpu t rates of iron, molybdenum, and bromine correlated, albeit poorly, wi th biliary glutathione efflux (r values: iron, 0.67; molybdenum, 0.40; bromine, 0.53; respectively). Copper, manganese, and zinc secretion d id not show any consistent relationship with glutathione secretion. Th e secretion rates of iron, molybdenum, and bromine, like that of calci um, showed a highly significant correlation with bile flow (r values: iron, 0.89; molybdenum, 0.75; bromine, 0.80; and calcium, 0.90; respec tively, p < 0.001). Multiple regression analysis, with trace element s ecretion as the dependent variable and bile flow and glutathione secre tion as the independent variables, revealed that bile flow, but not gl utathione, significantly contributes to regulation of trace element se cretion. Bile secretion of iron, molybdenum, and bromine also signific antly correlated with that of the freely permeable cation potassium, w ith intercepts of the regression lines near zero. The data indicate th at glutathione does not ploy a direct regulatory role in bile secretio n of the major endogenous trace elements in rats. However, biliary glu tathione indirectly provides a driving force for the secretion of iron , molybdenum, and bromine by Stimulating bile flow.