Influence of exogenous thiols on inorganic mercury-induced injury in renal proximal and distal tubular cells from normal and uninephrectomized rats.
Inorganic mercury (Hg(2+)) 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 Hg(2+) (not bound to a thiol). Preloading cells with glutathione increased Hg(2+)-induced cellular injury in PT cells from control rats. However, coincubation of PT or DT cells from control or NPX rats with Hg(2+) and glutathione (1:4) provided significant protection relative to incubations with Hg(2+) 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 Hg(2+) and cysteine (1:4) had little effect on, or slightly enhanced, Hg(2+)-induced cellular injury at low concentrations of Hg(2+) in all cells studied. Coincubation with Hg(2+) and albumin (1:4) markedly protected PT and DT cells from control and NPX rats at all concentrations except the highest concentration of Hg(2+) in DT cells from NPX rats. 2,3-Dimercapto-1-propanesulfonic acid protected cells both when preloaded or added simultaneously with Hg(2+). Thus, renal cells from NPX rats are more susceptible to Hg(2+)-induced injury, PT and DT cells respond differently to exposure to Hg(2+), and thiols can significantly modulate the toxic response to Hg(2+).
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Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan 48201-1928, USA. l.h.lash@wayne.edu
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D000418:Albumins / Q000494:pharmacology; D000818:Animals; D003545:Cysteine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005978:Glutathione / Q000494:pharmacology*; D007287:Inorganic Chemicals / Q000633:toxicity*; D007684:Kidney Tubules / Q000187:drug effects*; D007686:Kidney Tubules, Distal / Q000187:drug effects; D007687:Kidney Tubules, Proximal / Q000187:drug effects; D008297:Male; D008628:Mercury / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014494:Unithiol / Q000494:pharmacology; D005723:gamma-Glutamyltransferase / Q000502:physiology*
D000418:Albumins; D007287:Inorganic Chemicals; D014494:Unithiol; D005723:gamma-Glutamyltransferase; D008628:Mercury; D005978:Glutathione; D003545:Cysteine