Renal glutathione and mercury uptake by kidney.
The kidney is well documented as the target organ for mercuric ion. Mechanisms by which this ion accumulates in renal tissue, however, are less well understood. Sulfhydryl groups in renal tissue might well bind this metal and serve as a sink for its accumulation. Various studies have indicated that both methyl mercury as well as mercuric ion are accumulated less by renal tissue after depletion of nonprotein sulfhydryl groups. A similar reduction in hepatic accumulation of mercuric ion or methyl mercury does not occur after nonprotein sulfhydryl depletion. This observation may relate to the higher tissue content of nonprotein sulfhydryls in liver than kidney or to a fundamentally different mechanism of metal uptake. Mercuric ion accumulation by renal tissue also can be reduced by ureteral occlusion, a reduction that is less than that for inulin in comparable experiments. These data are complex and do not clearly establish a role for filtration in the delivery of mercury to the kidney. Inhibition of the renal enzyme gamma-glutamyl transpeptidase (gamma-GT) results in a marked increase in the excretion of both glutathione and mercury in the urine. Although there is a tendency for kidneys of the gamma-GT-inhibited animals to contain less mercury than controls, the change in renal content was not significant. These observations suggest that gamma-GT may have a role in the reabsorption of mercury from the tubular lumen. Interestingly, both mercuric chloride-induced mortality and effects on renal slice accumulation of organic ions were enhanced in the presence of nonprotein sulfhydryl depletion caused both by immediate depletion of the glutathione pool and by inhibition of its synthesis.
D000818:Animals; D004229:Dithiothreitol / Q000494:pharmacology; D005919:Glomerular Filtration Rate; D005978:Glutathione / Q000378:metabolism*; D007444:Inulin; D007668:Kidney / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008628:Mercury / Q000378:metabolism*; D008630:Mercury Poisoning / Q000378:metabolism; D008871:Microvilli / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D013438:Sulfhydryl Compounds / Q000378:metabolism
D013438:Sulfhydryl Compounds; D007444:Inulin; D008628:Mercury; D005978:Glutathione; D004229:Dithiothreitol