Alterations in organic ion transport induced by gentamicin nephrotoxicity in the rat

William M. Bennett, Charles E. Plamp, Richard A. Parker, David N. Gilbert, Donald C. Houghton, George A. Porter

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Abstract

The effect of gentamicin, an aminoglycoside antibiotic, on the transport of PAH and NMN was measured in renal cortical slices of male Fischer rats pretreated with 40 mg/kg/day. Experimental animals or saline controls were sacrificed at intervals following 1 to 14 days of injections. Gentamicin-treated rats developed polyuria and azotemia after 3 to 7 days, respectively, whereas control animals remained normal. PAH transport was enhanced prior to the onset of azotemia in slices from rats given gentamicin as compared to controls. The early stimulation of PAH transport in gentamicin-treated rats was followed by a decrease in transport on days 10 and 14. The mechanism of the enhanced PAH transport is unclear, although gentamicin did impair run-out of PAH from cortical slices. Enhanced PAH transport was blocked by iodoacetate, a metabolic inhibitor, suggesting that this phenomenon is an energy-requiring process. Effects of acetate and gentamicin on PAH uptake are additive, suggesting that the aminoglycosides stimulate organic acid transport by a mechanism different from that seen with acetate alone. NMN transport showed progressive impairment with time in treatment animals. The organic ion transport pattern, consisting of early stimulation and late suppression of PAH transport, appears to be characteristic of gentamicin doses which are nephrotoxic to the rat. Impaired NMN transport is an early abnormality which appears prior to overt gentamicin-induced renal failure. This may represent the most subtle tubular injury in the rat model of gentamicin nephrotoxicity.

Original languageEnglish (US)
Pages (from-to)32-39
Number of pages8
JournalThe Journal of Laboratory and Clinical Medicine
Volume95
Issue number1
StatePublished - Jan 1980

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Bennett, W. M., Plamp, C. E., Parker, R. A., Gilbert, D. N., Houghton, D. C., & Porter, G. A. (1980). Alterations in organic ion transport induced by gentamicin nephrotoxicity in the rat. The Journal of Laboratory and Clinical Medicine, 95(1), 32-39.