Mercuric chloride cytotoxicity in isolated proximal tubular cells from uninephrectomized and sham-operated rats
- Mercer Univ., Macon, GA (United States) Wayne State Univ., Detroit, MI (United States)
The remaining renal tissue, in rats that have undergone uninephrectomy and compensatory renal growth (NPX) alone, or have also been treated with a low dose of mercuric chloride, contains more glutathione (GSH) per gram tissue than the renal tissue in sham-operated (SO) rats treated identically. In addition, NPX rats are more susceptible to the nephrotoxic effects of low toxic doses of mercuric chloride than are SO rats. To study the mechanisms for these differences, mercuric chloride-induced cytotoxicity was examined in freshly isolated proximal tubular cells from both NPX and SO rats. Cytotoxicity, as assessed by release of lactate dehydrogenase (LDH), exhibited a steep concentration dependence. During three hours, no cytotoxicity was observed at concentration of mercuric chloride below 0.15 mM. However, at concentrations of 0.25 mM and above, mercuric chloride induced cellular necrosis in almost all the cells as evidenced by loses of 80 to 90% of the total content of LDH. In the absence of bovine serum albumin in the incubating medium, the threshold for cytotoxicity was an order of magnitude lower. Cells from NPX and SO rats exhibited no differences in the pattern of injury. Preincubation of proximal tubular cells with 0.25 mM or higher of the thiol containing compounds GSH, cysteine, or dithiothreitol, or the chelating agent 2,3-dimercapto-1-propanesulfonate, completely protected the cells from the cytotoxic effects of 0.25 mM mercuric chloride. Protection was not afforded to proximal tubular cells when they were preincubated with the sulfhydryl alkylating agent N-ethylmaleimide. The authors findings indicate that the increased susceptibility of NPX rats to the nephropathy induced by mercuric chloride may be due to extrarenal factors. Their findings also show that low molecular weight thiol containing compounds protect proximal tubular cells from the nephrocytotoxic effects of mercuric chloride in vitro.
- OSTI ID:
- 5904984
- Report Number(s):
- CONF-9104107-; CODEN: FAJOE
- Journal Information:
- FASEB Journal (Federation of American Societies for Experimental Biology); (United States), Vol. 5:4; Conference: 75. annual meeting of the Federation of American Societies for Experimental Biology (FASEB), Atlanta, GA (United States), 21-25 Apr 1991; ISSN 0892-6638
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ANIMAL CELLS
NECROSIS
LACTATE DEHYDROGENASE
SECRETION
MERCURY
TOXICITY
CHELATING AGENTS
CYSTEINE
GLUTATHIONE
RATS
THIOLS
TUBULES
AMINO ACIDS
ANIMALS
BODY
CARBOXYLIC ACIDS
DRUGS
ELEMENTS
ENZYMES
HEMIACETAL DEHYDROGENASES
KIDNEYS
MAMMALS
METALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
OXIDOREDUCTASES
PATHOLOGICAL CHANGES
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RODENTS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology