Cisplatin Induce Urinary Space Obstruction and Tubular Necrosis in Rat Kidney

Introduction: Cisplatin is a platinum based antineoplastic drug, which is widely used for treatment of solid tumors. The present investigation was carried out to study the nephrotoxic effects of double dose injection of cisplatin in rats, as an experimental model. Methods: In this experimental study, 45 adult male Sprague Dawley rats with average weight of 200&plusmn;30 g were randomly divided into two experimental (n=30) and one control (n=15) groups. Rats of experimental groups received two repeated doses of cisplatin intraperitoneally (2.5 mg/kg, experimental group E1 & 5 mg/kg, experimental group E2) in the beginning of first and fifth week of the experiment. Eight weeks after injection, rats of all groups were given deep anesthesia and killed. Blood samples were collected directly from their hearts for biochemical evaluation. Tissue samples were removed and prepared sections were stained with H&E, PAS, Masson trichrome, and PNA methods. Prepared microscopic slides were utilized for both histopathological and morphometrical studies. Collected data were analyzed by ANOVA and Tukey post hoc test using SPSS. Results: Cisplatin administration induced a significant decrease in urinary space diameter of renal corpuscles in the experimental groups compared to the control group. This ultimately led to the urinary space obstruction in up to 95% of nephrons in experimental groups (P<0.001). There were significant difference between control and experimental groups (P<0.001) with regard to epithelial thickness of collecting duct, proximal and distal convoluted tubules. Moreover, there was a significant difference between control and experimental groups (P<0.001) with regard to the diameter of vasa recta. Acute tubular necrosis and urinary space obstruction were the main histological features of the experimental groups. There were also a significant elevation in serum level of BUN and creatinine in experimental group compared to those of control group. Conclusion: Cisplatin induces acute tubular necrosis and urinary space obstruction and some other morphological changes in rat kidney, in a dose dependent manner.