Gentamicin-induced nephrotoxicity varies temporally, with a peak being observed when this antibiotic is administered during the resting period and a trough when given during the activity period of rats. These variations are modified by fasting and by restricted feeding schedules. In this study, food and water intakes of adult female Sprague-Dawley rats were measured during pre-treatment (days 1 to 5) and during treatment (days 6 to 10) with gentamicin (80 mg/kg/day, i.p.) injected at 1300 h or 0100 h. A significantly higher level of serum creatinine was observed when gentamicin was administered at 1300 h compared to 0100 h, and a significantly lower creatinine clearance was found in rats treated with gentamicin at 1300 h compared to those treated with saline at the same time. Gentamicin treatment at 1300 h or 0100 h resulted in a decrease in the 24 h food intake. In addition, in the gentamicin-treated group at 0100 h, the maximal food intake observed at late dark during the pre-treatment period decreased during treatment, and early dark rather than late dark maximal intake occurred. Our data demonstrate that gentamicin induces a nephrotoxicity that varies temporally, and that gentamicin treatment inhibits food intake and alters its nocturnal variations.

Macronutrient composition of food was shown to have a potent impact in modulating circadian rhythms of gentamicin toxicity. In the present study, adult female Sprague-Dawley rats fully adapted to isocaloric 20 casein-containing, 20% soy-containing (both semi-purified with 10% safflower oil and 58.55% carbohydrate) or a standard chow diet (non-purified with 18.1% mixed proteins, 4.5% fat and 57.3% carbohydrate) were chronically treated for 10 days with a nephrotoxic dose of gentamicin sulfate (40 mg/kg/day, i.p.) or a saline solution given in the middle of their resting period or in the middle of their activity period. Body weights, 24-h, 12-h light and 12-h dark food intakes were measured before (Days 1 to 5) and during treatment (Days 6 to 15). Gentamicin nephrotoxicity indices including serum creatinine, creatinine clearance, urinary proteins, urinary enzymes activities, corticocefular regeneration and cortical accumulation of gentamicin were measured at specific time points during the experiment. (Abstract shortened by UMI.)

All aminoglycosides have the potential to cause nephrotoxicity. Previous studies have shown that this toxicity was altered according to the macronutrient composition of dietary regimens offered to female rats. In a first study, adult female Sprague-Dawley rats adapted to a standard chow diet, the standard chow with 20% added casein or with 55% added casein were treated for 10 days with a nephrotoxic dose of gentamicin sulfate (40 mg/kg/day, i.p.) or a saline solution. Food ingestion patterns and gentamicin nephrotoxicity indices were measured. In a second study, rats were fed the same diets, however, the treatment given was a sham injection. Results suggest that chronic gentamicin treatment leads to a decrease in food intake and flattening of the rhythms of food ingestion. Also, chow feeding and chow added with 20% casein were found to be more protective against gentamicin-induced nephrotoxicity than chow added with 55% casein.

No description available.

No description available.

No description available.