Stein A F, Gregus Z, Klaassen C D
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66103.
Toxicol Appl Pharmacol. 1988 May;93(3):351-9. doi: 10.1016/0041-008x(88)90037-3.
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.
甲基汞的胆汁排泄被认为与大鼠体内非蛋白硫醇的胆汁排泄有关。谷胱甘肽(GSH)及相关硫醇的胆汁排泄在物种间的差异尚不清楚;因此,研究了五种物种中GSH相关硫醇的胆汁排泄与甲基汞之间的关系。小鼠、大鼠、仓鼠、豚鼠和兔子的GSH相关硫醇和二硫化物的胆汁排泄率分别为369、192、94、50和19 nmol/分钟/千克。小鼠、仓鼠和大鼠胆汁中的主要硫醇是GSH,而豚鼠和兔子胆汁中主要含半胱氨酰甘氨酸(Cys-Gly)。豚鼠和兔子胆汁中Cys-Gly的比例较高,这与它们肝脏中γ-谷氨酰转肽酶(GGT)的活性高于其他物种有关。小鼠、大鼠和仓鼠的甲基汞胆汁排泄率(nmol/分钟/千克)约为0.8,相比之下,豚鼠和兔子的排泄率明显较低(分别为0.15和0.03)。研究得出结论,胆汁中GSH相关硫醇和二硫化物的物种特异性组成与肝脏GGT活性的物种差异有关,并且GSH相关硫醇胆汁排泄的物种差异并不能完全解释甲基汞排泄的物种差异,这表明其他因素显然也参与了决定甲基汞胆汁排泄率的过程。