Experimental gentamicin nephrotoxicity

Effect of streptozotocin-induced diabetes

W. C. Elliott, Donald Houghton, D. N. Gilbert, J. Baines-Hunter, W. M. Bennett

Research output: Contribution to journalArticle

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Abstract

To determine the effect of diabetes mellitus on gentamicin nephrotoxicity we treated male F344 rats with streptozotocin 22 mg/kg (DM rats). DM rats were compared to controls (C) and nondiabetic rats ingesting the osmotic diuretic isosorbide administered to simulate glycosuric diuresis (C/I). Base-line C/I renal function and histology did not differ from C. However, in DM rats base-line inulin clearance (C(IN)) was 20% lower, and renal cortical slice uptake of p-aminohippurate was reduced compared to C and C/I. DM rats also had foci of renal tubular epithelial dysplasia not seen in C or C/I. Gentamicin was administered at 40 mg/kg-day to C and C/I and 32 mg/kg-day to DM rats to adjust for base-line C(IN). Acute tubular necrosis, associated with depression of C(IN) and renal cortical p-aminohippurate and N-methylnicotinamide uptake, developed in all three groups. There were no differences between C and C/I. However, the degree of acute tubular necrosis and dysfunction was less in DM rats than C and C/I. Renal cortical gentamicin accumulation was also slower in DM than either C ir C/I, and changes in renal cortical gentamicin over time followed a different pattern in DM rats. These results indicate that 1) attenuation of gentamicin injury in DM rats may be related to reduced accumulation of gentamicin by the renal cortex, 2) this reduced accumulation may be due to subtle base-line tubular injury mediated by streptozotocin or the diabetic state, and 3) osmotic diuresis does not account for attenuation of renal injury in DM.

Original languageEnglish (US)
Pages (from-to)264-270
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume233
Issue number1
StatePublished - 1985

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Experimental Diabetes Mellitus
Gentamicins
Kidney
p-Aminohippuric Acid
Diuresis
Streptozocin
Osmotic Diuretics
Wounds and Injuries
Necrosis
Isosorbide
Inulin
Inbred F344 Rats
Histology
Diabetes Mellitus

ASJC Scopus subject areas

  • Pharmacology

Cite this

Experimental gentamicin nephrotoxicity : Effect of streptozotocin-induced diabetes. / Elliott, W. C.; Houghton, Donald; Gilbert, D. N.; Baines-Hunter, J.; Bennett, W. M.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 233, No. 1, 1985, p. 264-270.

Research output: Contribution to journalArticle

Elliott, WC, Houghton, D, Gilbert, DN, Baines-Hunter, J & Bennett, WM 1985, 'Experimental gentamicin nephrotoxicity: Effect of streptozotocin-induced diabetes', Journal of Pharmacology and Experimental Therapeutics, vol. 233, no. 1, pp. 264-270.
Elliott, W. C. ; Houghton, Donald ; Gilbert, D. N. ; Baines-Hunter, J. ; Bennett, W. M. / Experimental gentamicin nephrotoxicity : Effect of streptozotocin-induced diabetes. In: Journal of Pharmacology and Experimental Therapeutics. 1985 ; Vol. 233, No. 1. pp. 264-270.
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