BACKGROUND: Cisplatin (cis-diamminedichloroplatinum II; CDDP) is used widely as an antitumor drug in clinics, but is accompanied with renal toxicity. The present study was designed to compare the effect of losartan and vitamin E as prophylaxes against CDDP-induced nephrotoxicity. METHODS: Thirty-two Wistar rats were divided into 5 groups: group 1 receiving losartan 10 mg/kg; group 2, vitamin E in almond oil 1 g/kg; group 3, combination of group 1 and 2 regimens; group 4, almond oil; and group 5, negative control group. All groups were treated for a 4-day period, but at day 3, groups 1-4 received a single dose (6 mg/kg) of CDDP. The animals were sacrificed 1 week after CDDP administration. RESULTS: Animals' weight did not change significantly, but increasing blood urea nitrogen and malondialdehyde levels were observed statistically in all CDDP-treated animals. No detectable change was observed in nitrite level, but serum osmolality in groups 1, 2 and 4 was different from that for group 5 (p<0.05). Kidney damage scoring showed no significant difference between group 2 and the negative control group (group 2: 1.0 ± 0.24; group 5: 0.40 ± 0.10; p>0.05) but a statistically significant difference from the positive control group (p<0.05). The tubular damage score of group 1 also was not statistically significantly different from that of the negative control group. CONCLUSIONS: Although vitamin E or losartan as prophylaxes demonstrated some protective effects, the combination of losartan and vitamin E did not protect against CDDP-induced nephrotoxicity, for unknown reasons which may relate to pharmacokinetic or pharmacodynamic drug interactions.
BACKGROUND:Cisplatin (cis-diamminedichloroplatinum II; CDDP) is used widely as an antitumor drug in clinics, but is accompanied with renal toxicity. The present study was designed to compare the effect of losartan and vitamin E as prophylaxes against CDDP-induced nephrotoxicity. METHODS: Thirty-two Wistar rats were divided into 5 groups: group 1 receiving losartan 10 mg/kg; group 2, vitamin E in almond oil 1 g/kg; group 3, combination of group 1 and 2 regimens; group 4, almond oil; and group 5, negative control group. All groups were treated for a 4-day period, but at day 3, groups 1-4 received a single dose (6 mg/kg) of CDDP. The animals were sacrificed 1 week after CDDP administration. RESULTS: Animals' weight did not change significantly, but increasing blood ureanitrogen and malondialdehyde levels were observed statistically in all CDDP-treated animals. No detectable change was observed in nitrite level, but serum osmolality in groups 1, 2 and 4 was different from that for group 5 (p<0.05). Kidney damage scoring showed no significant difference between group 2 and the negative control group (group 2: 1.0 ± 0.24; group 5: 0.40 ± 0.10; p>0.05) but a statistically significant difference from the positive control group (p<0.05). The tubular damage score of group 1 also was not statistically significantly different from that of the negative control group. CONCLUSIONS: Although vitamin E or losartan as prophylaxes demonstrated some protective effects, the combination of losartan and vitamin E did not protect against CDDP-induced nephrotoxicity, for unknown reasons which may relate to pharmacokinetic or pharmacodynamic drug interactions.