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-induced x-ray emission under various conditions with altered biliary glutathione secretion and hepatic glutathione content in the rat. Treatment 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%, and -95%, respectively, and in hepatic glutathione content of -0%, +25%, and -86%, respectively, when compared with control values. Biliary glutathione 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 analysis; the apparent choleretic activity of glutathione was 67 microliters/mumol. Six trace elements (iron, zinc, copper, manganese, molybdenum, bromine) could always be detected in bile. Potassium and calcium were measured for comparative purposes. No relation was found between biliary trace element secretion and hepatic glutathione content. Biliary output rates of iron, molybdenum, and bromine correlated, albeit poorly, with biliary glutathione efflux (r values: iron, 0.67; molybdenum, 0.40; bromine, 0.53; respectively). Copper, manganese, and zinc secretion did not show any consistent relationship with glutathione secretion. The secretion rates of iron, molybdenum, and bromine, like that of calcium, showed a highly significant correlation with bile flow (r values: iron, 0.89; molybdenum, 0.75; bromine, 0.80; and calcium, 0.90; respectively, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)