Tanaka T, Naganuma A, Imura N
Department of Public Health, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Toxicology. 1990 Mar 16;60(3):187-98. doi: 10.1016/0300-483x(90)90142-4.
The role of renal glutathione (GSH) metabolism as a mediating factor in the renal uptake and toxicity of inorganic mercury was investigated in mice by preadministering a gamma-glutamyltranspeptidase (GGT) inhibitor, acivicin. Pretreatment with acivicin (0.25, 1.0 or 2.5 mmol/kg, i.p.) led to a dose-dependent decrease in renal mercury content and increases in mercury and GSH contents in urine measured 2 h after HgCl2 injection (18 mumol/kg, i.v.). Acivicin pretreatment also ameliorated the renal and lethal toxicity caused by administration of inorganic mercury. Treatment of the mice with 1,2-dichloro-4-nitrobenzene (DCNB, 2.5 mmol/kg, i.p.), a specific depletor of hepatic GSH, prior to HgCl2 injection substantially reduced renal Hg content and consequently reduced the renal damage. In addition, coadministration of GSH (36 mumol/kg, i.v.) with HgCl2 increased the renal Hg content measured 5 min after HgCl2 injection to 2.6 fold higher than that of mice treated with HgCl2 alone. These results suggest that renal uptake of inorganic mercury, which is supposedly transported to the kidney as a mercury-GSH complex, is dependent on a reaction catalyzed by GGT on the outer surface of the renal brush border membrane in the same manner as the metabolism of GSH.
通过预先给予γ-谷氨酰转肽酶（GGT）抑制剂阿西维辛，在小鼠中研究了肾脏谷胱甘肽（GSH）代谢作为无机汞肾脏摄取和毒性的介导因子的作用。用阿西维辛（0.25、1.0或2.5 mmol/kg，腹腔注射）预处理导致肾脏汞含量呈剂量依赖性下降，并在注射HgCl2（18 μmol/kg，静脉注射）后2小时测量的尿液中汞和GSH含量增加。阿西维辛预处理还改善了无机汞给药引起的肾脏毒性和致死毒性。在注射HgCl2之前，用1,2-二氯-4-硝基苯（DCNB，2.5 mmol/kg，腹腔注射）处理小鼠，DCNB是肝脏GSH的特异性消耗剂，可显著降低肾脏汞含量，从而减少肾脏损伤。此外，将GSH（36 μmol/kg，静脉注射）与HgCl2共同给药，使注射HgCl2后5分钟测量的肾脏汞含量比单独用HgCl2处理的小鼠高出2.6倍。这些结果表明，无机汞的肾脏摄取可能以汞-GSH复合物的形式转运到肾脏，其依赖于肾刷状缘膜外表面上由GGT催化的反应，其方式与GSH的代谢相同。
