de Ceaurriz J, Payan J P, Morel G, Brondeau M T
Laboratoire de Chimie-Toxicologie de l'Environnement, Faculté de Pharmacie, Chatenay-Malabry, France.
J Appl Toxicol. 1994 May-Jun;14(3):201-6. doi: 10.1002/jat.2550140310.
The role of extracellular glutathione (GSH) and membrane-bound gamma-glutamyltranspeptidase (gamma-GT) as contributory factors in the disposition and toxicity of inorganic mercury (HgCl2, 1 mg kg-1, i.p.) was investigated in rats pretreated with acivicin (AT-125, 10 mg kg-1), a gamma-GT inhibitor. A high degree of gamma-GT inhibition (75%) and of protection (90%) against HgCl2-induced nephrotoxicity was obtained in gamma-GT-inhibited rats 24 h post-treatment. Pretreatment with acivicin affected the fractional distribution profile of 203 Hg, resulting in a twofold decrease in the renal incorporation of mercury 4 h post-treatment and a threefold increase in the 24-h urinary excretion of mercury. Plasma radioactivity remained constant over 24 h in rats dosed with 203Hg alone, whereas it decreased by 60% between 4 h and 24 h in gamma-GT-inhibited rats. In gamma-GT-inhibited rats treated with HgCl2 the renal and plasma reduced glutathione (GSH) content increased by 68% and 330% respectively, as compared to controls. The gamma-GT inhibition affected the distribution profile of mercury within urinary proteins, shifting the binding of mercury from the high-molecular-weight fraction (3% against 80%) to the low-molecular-weight fraction (72% against 10%). A significant but less impressive shift of mercury from the high- to the low-molecular-weight fraction also arose in the plasma. These results taken together support the pivotal role of extracellular GSH and membrane-bound gamma-GT in the renal incorporation, toxicity and excretion of inorganic mercury in rats.
在用阿西维辛（AT - 125，10 mg/kg）（一种γ-谷氨酰转肽酶抑制剂）预处理的大鼠中，研究了细胞外谷胱甘肽（GSH）和膜结合γ-谷氨酰转肽酶（γ-GT）作为无机汞（HgCl₂，1 mg/kg，腹腔注射）处置和毒性的促成因素的作用。在γ-GT抑制的大鼠中，处理后24小时获得了高度的γ-GT抑制（75%）和对HgCl₂诱导的肾毒性的保护（90%）。用阿西维辛预处理影响了²⁰³Hg的分数分布概况，导致处理后4小时肾脏中汞的掺入量减少两倍，汞的24小时尿排泄量增加三倍。单独给予²⁰³Hg的大鼠血浆放射性在24小时内保持恒定，而在γ-GT抑制的大鼠中，其在4小时至24小时之间下降了60%。与对照组相比，在用HgCl₂处理的γ-GT抑制的大鼠中，肾脏和血浆中还原型谷胱甘肽（GSH）含量分别增加了68%和330%。γ-GT抑制影响了汞在尿蛋白中的分布概况，使汞的结合从高分子量部分（3%对80%）转移到低分子量部分（72%对10%）。血浆中汞也出现了从高分子量部分到低分子量部分的显著但不太明显的转移。综合这些结果支持细胞外GSH和膜结合γ-GT在大鼠无机汞的肾脏掺入、毒性和排泄中起关键作用。
