Sulfobromophthalein inhibition of glutathione and methylmercury secretion into bile

The mechanism through which sulfobromophthalein (BSP) inhibits the biliary secretion of glutathione (GSH) and methylmercury was examined in male rats anesthetized with pentobarbital sodium. The biliary secretion rates of GSH and methylmercury were measured following the bolus intravenous administration of various doses of BSP, the GSH conjugate of BSP (BSP-SG), and phenol-3,6-dibromphthalein disulfonate (DBSP, a nonmetabolizable analogue of BSP). The effects of BSP on GSH secretion were dose dependent; at a dose of 120 mumol/kg the rate of GSH secretion fell close to zero. DBSP also inhibited GSH secretion, although the inhibition was not as complete as observed after BSP administration; at a dose of 180 mumol/kg GSH secretion fell to 18% of control. BSP-SG, in contrast, had no effect on GSH secretion into bile when given at a dose of 120 mumol/kg. At doses of 240 and 360 mumol BSP-SG/kg, there were only minor changes in the rate of GSH secretion. The changes in GSH secretion induced by these dyes were accompanied by proportional changes in glutathione disulfide (GSSG) secretion into bile, so that the molar ratio of GSSG to GSH in bile remained within the range of 0.07-0.18. In all experiments the changes in methylmercury secretion were parallel to the changes in GSH secretion. The results suggest that the BSP-induced inhibition of GSH, GSSG, and methylmercury secretion into bile is due to the direct inhibition of the biliary GSH transport process.