Nonprotective Role of Losartan in Cisplatin-Induced Nephrotoxicity in Ovariectomized Rat Model Treated With Estradiol Publisher



Ghadirian F^{1, 2} ; Nematbakhsh M^{1, 3, 4} ; Roozbehani S² ; Mazaheri S¹ ; Talebi A⁵ ; Pezeshki Z¹ ; Ashrafi F⁶ Show Affiliations
Source: Journal of Pharmaceutical Negative Results Published:2015

Abstract

Objective: The aim was to study the role of losartan on cisplatin (CP).induced nephrotoxicity in an estradiol replacement rat model. Materials and Methods: Forty.seven female Wistar rats were ovariectomized and divided into seven groups. Groups 1 and 2 were treated with placebo (sesame oil) on a weekly basis for 4 weeks, and then they received saline or CP (2.5 mg/kg/day) for the next 7 days, respectively. Group 3 received estradiol (250 μg/kg/week) for 4 weeks, and then treated with losartan (10 mg/kg/day) for the next 10 days while from day 3; they also received CP for 7 days. Group 4 had treatment regimen the same as Group 3, except saline instead of losartan. Groups 5 and 6 were treated similar to Groups 3 and 4, respectively, but the dose of estradiol was doubled. Finally, Group 7 was treated as Group 3 except vehicle instead of estradiol. At the end of the experiment, blood samples were obtained to measure blood urea nitrogen (BUN), creatinine (Cr), nitric oxide metabolite (nitrite) and malondialdehyde (MDA). The kidney tissues were also subjected to pathology investigations. Results: Cisplatin significantly increased the serum level of BUN, Cr, and MDA (P < 0.05). CP also increased kidney weight (KW) and kidney tissue damage score (KTDS), and decreased bodyweight significantly (P < 0.05). There is a significant difference in KTDS, weight changes and serum level of MDA between positive control groups compared with the groups received combination of losartan and CP (P < 0.05). Conclusions: It seems that the estrogen could promote CP.induced nephrotoxicity. Losartan also did not intensify CP.induced nephrotoxicity. Accordingly, supplementation of losartan to attenuate CP.induced nephrotoxicity in ovariectomized model treated with estradiol is not suggested.