Species variations in biliary excretion of glutathione-related thiols and methylmercury

The biliary excretion of methylmercury is thought to be related to the biliary excretion of nonprotein thiols in rats. Species differences in biliary excretion of glutathione (GSH) and related thiols are unknown; therefore, the relationship between the biliary excretion of GSH-related thiols and methylmercury in five species was studied. The biliary excretion rate of GSH-related thiols and disulfides was 369, 192, 94, 50, and 19 nmol/min/kg for mice, rats, hamsters, guinea pigs, and rabbits, respectively. The main thiol in mouse, hamster, and rat bile was GSH, whereas guinea pig and rabbit bile contained mainly cysteinylglycine (Cys-Gly). The larger percentage of Cys-Gly in guinea pig and rabbit bile was correlated with their greater hepatic gamma-glutamyltranspeptidase (GGT) activity than that observed in the other species. The biliary excretion rate (nmol/min/kg) of methylmercury was approximately 0.8 in mice, rats, and hamsters compared to significantly lower rates in guinea pigs and rabbits (0.15 and 0.03, respectively). It is concluded that the species-specific composition of GSH-related thiols and disulfides in bile is related to species variations in hepatic GGT activity, and that the species variation in biliary excretion of GSH-related thiols does not entirely account for the species variation in methylmercury excretion, indicating other factors are also apparently involved in determining the rate of biliary excretion of methylmercury.