Dietary composition alters gentamicin-induced nephrotoxicity in rats

Previous studies have shown temporal variations in gentamicin-induced renal toxicity characterized by a peak when administered during the resting period and a trough during the active period. This time-dependent toxicity was also altered according to the macronutrient composition of dietary regimens offered to female rats. In the present study, adult female Sprague-Dawley rats were adapted to semipurified isocaloric diets containing 20% casein or soy-protein (10% fat each) or to a standard chow diet (18.1% mixed proteins; 4.5% fat). The animals were then chronically treated for 10 days with a nephrotoxic dose of gentamicin sulfate (40 mg/kg/day ip) or a saline solution administered in the middle of their resting period (1200 h) or in the middle of their activity period (0000 h). Body weights of rats injected in the middle of their resting period decreased over the last 6 days of gentamicin treatment. Total 12-h light and 12-h dark food intakes were decreased in gentamicin-treated rats. Rats fed the standard chow diet had significantly lower corticocellular regeneration, serum creatinine and blood urea nitrogen compared to those fed the casein- and soy-containing diets. The present study demonstrates that chronic gentamicin-induced renal toxicity varies temporally according to the time of administration and that a mixed protein diet containing a lower fat level can protect against gentamicin-induced nephrotoxicity.