Abstract
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 γ-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+.
Footnotes
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Send reprint requests to: Dr. Lawrence H. Lash, Department of Pharmacology, Wayne State University, School of Medicine, 540 East Canfield Ave., Detroit, MI 48201-1928. E-mail:l.h.lash{at}wayne.edu
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↵1 This work was supported by National Institute of Environmental Health Sciences Grant ES05157.
- Abbreviations:
- Hg2+
- inorganic mercury
- PT
- proximal tubular
- acivicin
- l-(αS,5S)-α-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid
- Cys
- l-cysteine
- DMPS
- 2,3-dimercapto-1-propanesulfonic acid
- DT
- distal tubular
- GGT
- γ-glutamyltransferase
- GSH
- glutathione
- LDH
- lactate dehydrogenase
- NPX
- uninephrectomized
- PAH
- p-aminohippurate
- Received April 8, 1999.
- Accepted June 30, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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Influence of Exogenous Thiols on Inorganic Mercury-Induced Injury in Renal Proximal and Distal Tubular Cells from Normal and Uninephrectomized Rats
