Effect of sodium intake on gentamicin nephrotoxicity in the rat

W. M. Bennett, M. N. Hartnett, D. Gilbert, Donald Houghton, G. A. Porter

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

To produce renal failure in rats takes many times the therapeutic dosage as used in man. It is known that acute renal failure in experimental animals may be enhanced by extracellular volume depletion. The present study provides histologic and electron microscopic evidence that sodium restriction by dietary means markedly potentiates renal failure. The mortality of 44% in sodium depleted animals correlates well with the severe pathologic changes observed. The mechanism of enhancement of the renal insult by volume depletion remains speculative; however, activation of the renal pressor system within the kidney is an attractive possibility that would be consistent with the present findings. The kidney has been assumed to excrete gentamicin almost entirely by glomerular filtration. Although the exact mechanism of nephrotoxicity is unknown, drug transported into the cell may damage organelles resulting in the appearance of organelle fragments within lysosomes and ultimately cell rupture, mainly in the proximal contorted tubular cells. Since concentrations of gentamicin in cortical tissue are increased by sodium depletion, it is tempting to speculate that the nephrotoxicity is related to enhanced intracellular concentration of gentamicin. To summarize, a low sodium diet markedly potentiates nephrotoxic effects of the drug as evidenced by animal mortality, renal failure, pathologic changes, and increased renal cortical concentration of the drug. High sodium intake reduces the cortical concentration of gentamicin but renal function and ultrastructure were similar to normally fed rats given the same dose.

Original languageEnglish (US)
Pages (from-to)736-738
Number of pages3
JournalProceedings of the Society for Experimental Biology and Medicine
Volume151
Issue number4
StatePublished - 1976

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Gentamicins
Rats
Sodium
Kidney
Animals
Renal Insufficiency
Organelles
Pharmaceutical Preparations
Dietary Sodium
Sodium-Restricted Diet
Nutrition
Mortality
Lysosomes
Acute Kidney Injury
Chemical activation
Rupture
Tissue
Electrons

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Effect of sodium intake on gentamicin nephrotoxicity in the rat. / Bennett, W. M.; Hartnett, M. N.; Gilbert, D.; Houghton, Donald; Porter, G. A.

In: Proceedings of the Society for Experimental Biology and Medicine, Vol. 151, No. 4, 1976, p. 736-738.

Research output: Contribution to journalArticle

Bennett, W. M. ; Hartnett, M. N. ; Gilbert, D. ; Houghton, Donald ; Porter, G. A. / Effect of sodium intake on gentamicin nephrotoxicity in the rat. In: Proceedings of the Society for Experimental Biology and Medicine. 1976 ; Vol. 151, No. 4. pp. 736-738.
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