EFFECTS OF FASTING ON TEMPORAL VARIATIONS IN NEPHROTOXICITY OF GENTAMICIN IN RATS

Evidence for temporal variations in the nephrotoxicity of low doses of aminoglycosides were recently shown by using specific and sensitive p arameters of renal toxicity, The aim of the present study was to evalu ate the effect of a short period of fasting on the temporal variations in the renal toxicity of gentamicin, Twenty-eight normally fed (i.e., food and water were available ad libitum throughout the experiment) f emale Sprague-Dawley rats (weight, 175 to 220 g) and 28 fasted rats (i .e., only water was available during a 12-h fast before and a 24.h fas t after gentamicin injection) were used, The animals were synchronized on a 14-h light, 10-h dark cycle (lights on at 0600 h) for 1 week bef ore gentamicin administration, In July 1993, each group of animals was treated with a single intraperitoneal injection of saline (NaCl, 0.9% ) or gentamicin (150 mg/kg of body weight) at either the peak (1400 h) or the trough (0200 h) of the previously determined toxicity, On day 1, the 24-h urinary excretion of beta-galactosidase, N-acetyl-beta-D-g lucosaminidase, and gamma-glutamyltransferase was significantly higher in normally fed animals treated with gentamicin at 1400 h than in the ir time-matched controls and in normally fed animals treated at 0200 h (P < 0.01), which had normal levels of these enzymes, By contrast, th e urinary excretion of these enzymes was significantly higher in both groups of gentamicin-treated, fasted rats than in their time-matched c ontrol groups (P < 0.01), reaching levels similar to those measured in normally fed rats treated at 1400 h, The accumulation of gentamicin w as significantly lower in the renal cortex of normally fed rats treate d at 0200 h than in rats treated at 1400 h (P < 0.05), but this time-d ependent difference was not found in fasted rats treated at 0200 and 1 400 h, Immunogold labeling done on ultrathin sections and observed by electron microscopy showed a similar subcellular localization of genta micin in normally fed and fasted rats treated at either 1400 or 0200 h , These results suggest that the feeding period is of crucial importan ce in the temporal variations of the nephrotoxicity of gentamicin in r ats.