Influence of exogenous thiols on inorganic mercury-induced injury in renal proximal and distal tubular cells from normal and uninephrectomized rats

作     者：Lash, LH Putt, DA Zalups, RK 

作者机构：Wayne State Univ Sch Med Dept Pharmacol Detroit MI 48201 USA Mercer Univ Sch Med Div Basic Med Sci Macon GA 31207 USA 

出 版 物：《JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS》 (药理学与实验治疗学杂志)

年 卷 期：1999年第291卷第2期

页      面：492-502页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：NIEHS NIH HHS [ES05157] Funding Source: Medline 

主　　题：白蛋白类/药理学 半胱氨酸/药理学 剂量效应关系 药物 药物相互作用 谷胱甘肽/药理学 无机化学品/毒性 肾小管/药物作用 肾小管 远端/药物作用 肾小管 近端/药物作用 汞/毒性 大鼠 Sprague-Dawley 时间因素 二巯丙磺钠/药理学 γ-谷氨酰转移酶/生理学 动物 男(雄)性 大鼠 

摘      要：Inorganic mercury (Hg2+) induced time- and concentration-dependent cellular injury in freshly isolated proximal tubular (PT) and distal tubular (DT) cells from normal (control) rats or uninephrectomized (NPX) rats. PT cells from NPX rats were more susceptible than PT cells from control rats, and DT cells were slightly more susceptible than PT cells to cellular injury induced by Hg2+ (not bound to a thiol). Preloading cells with glutathione increased Hg2+-induced cellular injury in PT cells from control rats. However, coincubation of PT or DT cells from control or NPX rats with Hg2+ and glutathione (1:4) provided significant protection relative to incubations with Hg2+ alone. No support was obtained for a role for gamma-glutamyltransferase in glutathione-dependent protection. However, the organic anion carrier does appear to play a role in accumulation and toxicity of mercuric conjugates of cysteine in PT cells from control, but not NPX, rats. Coincubation with Hg2+ and cysteine (1:4) had little effect on, or slightly enhanced, Hg2+-induced cellular injury at low concentrations of Hg2+ in all cells studied. Coincubation with Hg2+ and albumin (1:4) markedly protected PT and DT cells from control and NPX rats at all concentrations except the highest concentration of Hg2+ in DT cells from NPX rats. 2,3-Dimercapto-1-propanesulfonic acid protected cells both when preloaded or added simultaneously with Hg2+. Thus, renal cells from NPX rats are more susceptible to Hg2+-induced injury, PT and DT cells respond differently to exposure to Hg2+, and thiols can significantly modulate the toxic response to Hg2+.