Ontogenic aspects of cisplatin-induced nephrotoxicity in rats

A multi-age rat model was evaluated to identify a potential age-related difference in kidney injury following administration of cisplatin (CP). Different age groups of Wistar rats (aged 3, 7, 11 and 24 weeks) were given CP intraperitoneally (6 mg/kg) and sacrificed 6 days thereafter. CP-induced nephrotoxicity caused significant decreases in body weight, creatinine clearance, urine osmolality, plasma total anti-oxidant status, cortical glutathione (GSH) concentration and superoxide dismutase activity. It increased kidney weight and plasma concentrations of creatinine and urea. It increased urinary N-acetyl-beta-D-glucosaminidase activity and protein concentration. Most of the above actions were more marked as the animals advanced in age, except for the changes in GSH, which were similar in all age groups. CP produced necrosis in renal tubules and epithelial vacuolization, the extent of which was more evident as the rats grew older. Renal CP concentration was increased with the increased age of the animal, and the cortical CP concentration in 3 week-old rats was nearly half that of 24 week-old rats. This study showed that the vulnerability profile of each age group was different, suggesting that a multi-age pediatric/geriatric animal model is appropriate to assess, more completely, age-dependent changes in drug toxicity.