Laboratory Investigation
Kidney International (1983) 24, 178–184; doi:10.1038/ki.1983.142
Selective glutathione depletion on function and structure of the isolated perfused rat kidney
Mayer Brezis1, Seymour Rosen1, Patricio Silva1 and Franklin H Epstein1
1Charles A. Dana Research Institute, the Harvard-Thorndike Laboratory of Beth Israel Hospital, Departments of Medicine and Pathology, Beth
Israel Hospital, and Harvard Medical School, Boston, Massachusetts
Correspondence: Dr F H Epstein, Renal Division, Beth Israel Hospital, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
Received 5 August 1982; Revised 16 November 1982.
Top of pageAbstract
Selective glutathione depletion on function and structure of the isolated perfused rat kidney. The role of glutathione (GSH) in the preservation of
renal function and the pathogenesis of renal injury has been investigated using the isolated perfused rat kidney as a model. In kidneys perfused
for 80 min with 5 mM glucose as the only exogenous substrate, tissue GSH becomes depleted, renal function deteriorates, and a degenerative
change appears, restricted to the medullary thick ascending limb. These abnormalities can be ameliorated by providing amino acid supplements
or by adding GSH itself to the perfusion. To distinguish between the effects of amino acid supplementation and GSH depletion per se, selective
depletion of GSH was accomplished in several different ways. Synthesis of GSH was inhibited by the addition of dl-buthionine-SR-sulfoximine, a
specific inhibitor of gamma-glutamyl cysteine synthetase. GSH depletion was also produced by 2-cyclohexene-1-one and diethylmaleate, both
known to diminish the concentration of GSH selectively without affecting protein thiols. Perfused kidneys selectively depleted of GSH showed
significant impairment of concentrating ability, and less marked decreases in tubular reabsorption of sodium. The degenerative changes in the
medullary thick ascending limb, on the other hand, were unaltered. While GSH depletion seriously impairs certain renal transport functions, it is
probably not responsible for the anatomical disruption of the thick ascending limb that characterizes the isolated perfused rat kidney.
Kidney International (1983) 24, 178–184; doi:10.1038/ki.1983.142
Selective glutathione depletion on function and structure of the isolated perfused rat kidney
Mayer Brezis1, Seymour Rosen1, Patricio Silva1 and Franklin H Epstein1
1Charles A. Dana Research Institute, the Harvard-Thorndike Laboratory of Beth Israel Hospital, Departments of Medicine and Pathology, Beth
Israel Hospital, and Harvard Medical School, Boston, Massachusetts
Correspondence: Dr F H Epstein, Renal Division, Beth Israel Hospital, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
Received 5 August 1982; Revised 16 November 1982.
Top of pageAbstract
Selective glutathione depletion on function and structure of the isolated perfused rat kidney. The role of glutathione (GSH) in the preservation of
renal function and the pathogenesis of renal injury has been investigated using the isolated perfused rat kidney as a model. In kidneys perfused
for 80 min with 5 mM glucose as the only exogenous substrate, tissue GSH becomes depleted, renal function deteriorates, and a degenerative
change appears, restricted to the medullary thick ascending limb. These abnormalities can be ameliorated by providing amino acid supplements
or by adding GSH itself to the perfusion. To distinguish between the effects of amino acid supplementation and GSH depletion per se, selective
depletion of GSH was accomplished in several different ways. Synthesis of GSH was inhibited by the addition of dl-buthionine-SR-sulfoximine, a
specific inhibitor of gamma-glutamyl cysteine synthetase. GSH depletion was also produced by 2-cyclohexene-1-one and diethylmaleate, both
known to diminish the concentration of GSH selectively without affecting protein thiols. Perfused kidneys selectively depleted of GSH showed
significant impairment of concentrating ability, and less marked decreases in tubular reabsorption of sodium. The degenerative changes in the
medullary thick ascending limb, on the other hand, were unaltered. While GSH depletion seriously impairs certain renal transport functions, it is
probably not responsible for the anatomical disruption of the thick ascending limb that characterizes the isolated perfused rat kidney.