Role of NK1 receptors on cisplatin-induced nephrotoxicity in the rat

The role of NK1 receptors on the nephrotoxicity associated with cisplatin t reatment was evaluated. Adult Sprague-Dawley male rats (300-400 g) were tre ated with saline (0.1 ml/100 g, i.p., every 8 h for 72 h) or the selective NK1 receptor antagonist (GR205171; 2 mg/kg, i.p., every 8 h for 72 h). Trea tments were started 5 min before cisplatin (7.5 mg/kg, i.p., single dose). All evaluations were made from 72 h to 96 h after cisplatin. An oral load o f 10 ml/kg of water was given at lime 0 (72 h after cisplatin). Cisplatin reduced the urinary volume (-45%), creatinine clearance (>90%), l ithium clearance (-76%) and urinary potassium excretion (-54%). Protein and sodium excretion was not affected by cisplatin. GR205171 prevented the red uction in urine volume induced by cisplatin. Ln addition, the decreases in creatinine and lithium clearances induced by cisplatin were also attenuated by the NK1 receptor antagonist. The clearance of creatinine averaged 0.57/-0.2 ml/min in controls, 0.004+/-0.01 ml/min after cisplatin, and 0.09+/-0 .02 ml/min after cisplatin + GR205171. The lithium clearance was 0.09+/-0.0 4 ml/min in controls, 0.02+/-0.01 ml/min after cisplatin and 0.06+/-0.01 ml /min after cisplatin + GR205171. Cisplatin induced marked necrosis, vacuola tion and edema of proximal renal tubules; these changes were considerably r educed in GR205171-treated animals. These results indicate that treatment with a selective NK1 receptor antagon ist ameliorated cisplatin-induced renal toxicity in rats, as evidenced by i mprovements in renal function and histology.