Effect of fasting on temporal variation in the nephrotoxicity of amphotericin B in rats

Evidence for temporal variation in the. nephrotoxicity of amphotericin B wa s recently reported in experimental animals. The role of food in these. var iations was determined by studying the effect of a short fasting period on the temporal variation in the renal toxicity of amphotericin B. Twenty-eigh t normally fed and 28 fasted female Sprague-Dawley rats were used. Food was available ad libitum to the fed rats, while the fasted animals were fasted 12 h before and 24 h after amphotericin B injection to minimize stress for the animals. Water was available? ad libitum to both groups of rats, which were maintained on a 14-h light, 10-h dark regimen (light on at 0600 h). R enal toxicity was determined by comparing the levels of excretion of renal enzyme and the serum creatinine and blood urea nitrogen (BUN) levels at the time of the maximal (0700 h) or the minimal (1900 h) nephrotoxicity after the intraperitoneal administration of a single dose of dextrose (5%; contro l group) or amphotericin B (50 mg/kg of body weight; treated group) to the rats. The nephrotoxicities obtained after amphotericin B administration at both times of day were compared to the nephrotoxicities observed fur time-m atched controls. In fed animals, the 24-h urinary excretion of N-acetyl-bet a-D-glucosaminidase and P-galactosidase was significantly: higher when amph otericin B was injected at 0700 and 1900 h, The excretion of these two enzy mes was reduced significantly (P < 0.05) in fasting rats, and this effect w as larger at 0700 h (P < 0.05) than at 1900 h. The serum creatinine level w as also significantly higher (P < 0.05) in fed animals treated at 0700 h th an in fed animals treated at 1900 h. Easting reduced significantly (P < 0.0 5) the increase in the serum creatinine level, and this effect was larger i n the animals treated at 0700 h. Similar data were obtained for BUN levels, Amphotericin B accumulation was significantly higher (P < 0.05) in the ren al cortexes of fed rats than in those of fasted animals, but there was no d ifference according to the time of injection. These results demonstrated th at fasting reduces the nephrotoxicity of amphotericin B and that food avail ability is of crucial importance in the temporal variation in the renal tox icity of amphotericin B in rats.