Effects of uninephrectomy and mercuric chloride on renal glutathione homeostasis

RK Zalups and LH Lash

Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, Georgia.

The effects of uninephrectomy and i.v. injections of inorganic Hg on renal glutathione(GSH) homeostasis were studied in rats. Compensatory renal growth occurred in all uninephrectomized (NPX) rats 12 days after surgery. The weights of, and the amounts of total protein in, the remnant left kidneys from the NPX rats were significantly greater than those of the corresponding left kidneys from sham-operated (SHAM) rats. The concentration of GSH in samples of whole kidney, cortex and outer stripe of the outer medulla increased after uninephrectomy, with the most striking changes occurring in the outer stripe of the outer medulla. The concentration of GSH in all samples from the SHAM and NPX rats was greater after the administration of a low, nontoxic dose of HgCl2 (0.5-mumol/kg). As with uninephrectomy alone, the increases due to inorganic Hg in both SHAM and NPX rats were greatest in the outer stripe of the outer medulla. The concentration of GSH increased further with a higher, toxic dose of HgCl2 (2.0-mumol/kg). Increasing the dose of HgCl2 to 3.0-mumol/kg resulted in more severe damage to the kidneys of all rats and in decreased concentration of renal GSH. The concentration of Hg under the same conditions as above was also measured, and closely paralleled that of GSH, with the greatest differences occurring in the outer stripe of the outer medulla. To explain these results, we hypothesize that both during compensatory renal growth and after administration of low, nontoxic to mildly toxic doses of Hg, GSH synthesis is induced. At higher, more toxic doses of Hg, GSH depletion becomes more prominent.

Volume 254, Issue 3, pp. 962-970, 09/01/1990
Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics

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