Nonprotective role of losartan in cisplatin‑induced nephrotoxicity in ovariectomized rat model treated with estradiol

Authors

  • Fereshteh Ghadirian

Keywords:

Cisplatin, estrogen, losartan, nephrotoxicity, ovariectomized rats

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.

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Published

2015-01-28

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How to Cite

Nonprotective role of losartan in cisplatin‑induced nephrotoxicity in ovariectomized rat model treated with estradiol. (2015). Journal of Pharmaceutical Negative Results, 6(1), 2-6. https://pnrjournal.com/index.php/home/article/view/83