Biliary transport of glutathione and methylmercury

The hepatobiliary transport of glutathione (GSH) and methylmercury (MM) was investigated in male and female rats anesthetized with pentobarbital sodium. When bile flow was altered with either sodium dehydrocholate (DHC), hypertonic sucrose infusion, or by hypothermia, the absolute rates of GSH and MM secretion into bile were not affected, resulting in parallel concentration changes in the bile fluid for both GSH and MM. Indocyanine green and sulfobromophthalein (BSP), but not BSP-glutathione complex, inhibited the biliary secretion of free GSH. This inhibition was accompanied by a parallel inhibition of MM secretion into bile and occurred without any changes in liver GSH or MM levels. On the other hand, the intravenous administration of cysteine, GSH, and penicillamine was associated with an increase in the secretion rate of reduced sulfhydryl groups into bile and an increase in the biliary secretion rate of MM. The increased biliary secretion rate of MM after phenobarbital pretreatment was also associated with an increased rate of secretion of GSH into bile. In addition, sex differences and individual variability in the biliary secretion of MM were correlated with differing abilities to secrete GSH into bile. The results suggest the presence of a biliary transport system for GSH that determines the biliary secretion of MM.