[Preventive effect of urinastatin on cisplatin induced nephrotoxicity in rabbits]

The effect of urinastatin (US) on the prevention of cis-diamminedichloroplatinum (CDDP) induced nephrotoxicity was examined in experiments on rabbits. They were divided into seven groups and treated intravenously as follows: Group 1; intravenous injection of CDDP 3mg/kg only, Group 2; 3% sodium chloride (15ml/kg/h, 1h) + CDDP, Group 3; 3% sodium chloride + CDDP + US (10,000U/kg), Group 4; Hydration A (350ml/body) + 3% sodium chloride + CDDP, Group 5; Hydration A + 3% sodium chloride + CDDP + US, Group 6; Hydration B (200ml/body) + 3% sodium chloride + CDDP, Group 7; Hydration B + 3% sodium chloride + CDDP + US. Creatinine clearance (Ccr) value, arylamidase (AA) activity in urine and gamma-glutamyltranspeptidase (gamma-GTP) activity in urine were consecutively measured as indices of nephrotoxicity. Ccr values in groups 1-3 significantly decreased markedly whereas those in groups 4-7 did not. The change in AA activity and gamma-GTP activity in urine suggests that no nephrotoxicity occurred in groups 5 and 7. Consequently, this experiment indicated that nephrotoxicity was prevented when CDDP was administered in 200mg/body hydration with both 3% sodium chloride and US. The recommended dose of US seems to be a 2,000U/kg intravenous injection before CDDP administration, followed by 8,000U/kg intravenous drip infusion for 2 hours after CDDP administration.