Effect of cobalt on biliary excretion of bilirubin and glutathione

Adult male rats received cobaltous chloride (250 mumol/kg, sc) at various times (1-72 h) prior to assessment of hepatic heme oxygenase activity, bile flow, biliary concentration of bilirubin-glucuronides, and hepatic and biliary glutathione concentrations. Hepatic heme oxygenase activity increased 360% 24 h after treatment but returned to control levels by 72 h. Total biliary concentrations of the mono- and diglucuronides of bilirubin (BMG and BDG) were increased 47% at 24 h and returned to control levels more slowly than did heme oxygenase. Bile flow was not significantly changed at any time. Concentrations of hepatic reduced and oxidized glutathione (GSH and GSSG) tended to increase after cobalt, but changes were not statistically significant. Biliary GSH and GSSG increased 1 h after cobalt treatment and were twice control values 3 h after treatment. These biliary glutathione concentrations declined to the control range by 6 h. These results demonstrate that increased liver heme oxygenase activity following cobalt treatment may be associated with elevated biliary excretion of bilirubin glucuronides. However, changes that occurred in biliary excretion of glutathione in response to cobalt treatment were not accompanied by parallel changes in hepatic glutathione levels.