Temporal modulation of nephrotoxicity, feeding, and drinking in gentamicin-treated rats

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 nychthemeral 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 pretreatment (Days 1 to 5) and during treatment (Days 6 to 10) with gentamicin (80 mg/kg/day, i.p.) injected at 1300 or 0100h. 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 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 pretreatment 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.