Insulin reverses the protection given by diabetes against gentamicin nephrotoxicity in the rat

W. Gouvea, David Roth, H. Alpert, J. Kelley, V. Pardo, C. A. Vaamonde

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Abstract

Rats with untreated diabetes mellitus are protected from gentamicin- induced nephrotoxicity. In order to evaluate the role of hyperglycemia, glycosuria, and polyuria in this phenomenon, miniosmotic pumps filled with insulin were implanted for 15 days in seven female Sprague-Dawley rats with streptozotocin-induced diabetes mellitus. Plasma glucose levels were successfully maintained under 126 mg/dl. To serve as the control group, eight age-matched diabetic (plasma glucose >400 mg/dl) rats had miniosmotic pumps placed delivering only Ringer's solution. Six days after placement of the pumps, gentamicin (40 mg/Kg/day) was administered to all animals for 9 days. The insulin-treated diabetic rats exhibited clear signs of nephrotoxicity by Day 6 of gentamicin, whereas the diabetic control group remained free from any functional or morphological evidence of proximal tubular damage throughout the 9 days of the aminoglycoside administration. At the end of the experiment, the creatinine clearance in the insulin-treated diabetic group was 45% lower than in the untreated diabetic group (P < 0.005). In addition, there was a rise in plasma creatinine (P < 0.02), muramidase appeared in the urine, and mild patchy acute tubular necrosis of the renal cortex was observed by light microscopic examination. The insulin-treated group also accumulated more gentamicin in the renal cortex than the untreated animals (P < 0.005). It is concluded that protection against the nephrotoxic effects of gentamicin is a feature of untreated experimental diabetes mellitus in the rat and that correction of the hyperglycemic state with insulin reverses this resistance.

Original languageEnglish
Pages (from-to)445-453
Number of pages9
JournalProceedings of the Society for Experimental Biology and Medicine
Volume206
Issue number4
StatePublished - Jan 1 1994

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Medical problems
Gentamicins
Rats
Insulin
Experimental Diabetes Mellitus
Pumps
Plasmas
Creatinine
Diabetes Mellitus
Animals
Glycosuria
Kidney
Glucose
Polyuria
Control Groups
Aminoglycosides
Muramidase
Streptozocin
Hyperglycemia
Sprague Dawley Rats

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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Insulin reverses the protection given by diabetes against gentamicin nephrotoxicity in the rat. / Gouvea, W.; Roth, David; Alpert, H.; Kelley, J.; Pardo, V.; Vaamonde, C. A.

In: Proceedings of the Society for Experimental Biology and Medicine, Vol. 206, No. 4, 01.01.1994, p. 445-453.

Research output: Contribution to journalArticle

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