TEMPORAL VARIATION IN NEPHROTOXICITY OF LOW-DOSES OF ISEPAMICIN IN RATS

The temporal variation in the nephrotoxicity of low doses of isepamici n was studied in male Sprague-Dawley rats treated with a single daily intraperitoneal injection of saline (NaCl, 0.9%) or isepamicin (80 mg/ kg of body weight) at either 0800, 1400, 2000, or 0200 h for 4 and 10 days. On day 10, the cellular regeneration (incorporation of [H-3]thym idine into DNA of renal cortex) and cortical accumulation of isepamici n were significantly higher in animals treated at 1400 h than at 0200 h (P < 0.01). Immunogold labeling studies showed that isepamicin was e ssentially localized in the lysosomes of proximal tubular cells in all treated groups, but the density of the gold particles over the lysoso mes was higher in animals treated at 1400 than at 0200 h. The results of the present study show that the renal toxicity of isepamicin was ma ximal at 1400 h (midlight period) and minimal at 0200 h (middark perio d).