Administration of Vitamin E and Losartan As Prophylaxes in Cisplatin-Induced Nephrotoxicity Model in Rats Publisher Pubmed



Nematbakhsh M^{1, 2, 3} ; Ashrafi F^{1, 4} ; Safari T^{1, 3} ; Talebi A^{1, 5} ; Nasri H^{1, 2, 6} ; Mortazavi M^{2, 6} ; Khazaei M³ ; Baradaranmahdavi MM³ Show Affiliations
Source: Journal of Nephrology Published:2012

Abstract

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 CDDPtreated 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. © 2012 Societa Italiana di Nefrologia.