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Year : 2016  |  Volume : 26  |  Issue : 3  |  Page : 167-175

Nephroprotective effect of estrogen and progesterone combination on cisplatin-induced nephrotoxicity in ovariectomized female rats

1 Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
2 Water and Electrolytes Research Center; Department of Physiology, Isfahan University of Medical Sciences; Isfahan Institute of Basic and Applied Sciences Research, Isfahan, Iran
3 Department of Physiology, Hormozgan University of Medical Sciences, Isfahan, Iran
4 Department of Clinical Pathology, Isfahan University of Medical Sciences, Isfahan, Iran

Correspondence Address:
M Nematbakhsh
Department of Physiology, Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan
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Source of Support: This research was supported by Isfahan University of Medical Sciences, Conflict of Interest: None

DOI: 10.4103/0971-4065.160337

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Recently, we reported that estrogen (Es) has no beneficial effect on cisplatin (CP)-induced nephrotoxicity, but the role of progesterone (Pr) and the combination of Es and Pr are not yet well-defined. In this study, we investigated the protective role of Pr, and co-administration of Es/Pr on CP-induced nephrotoxicity. Eighty-six ovariectomized female Wistar rats were divided into 13 groups, and the experiments were performed in two phases. In Phase I, Groups 1–4 received 2, 5, 10, and 25 mg/kg, IM Pr dissolved in sesame oil every 5 days for four doses. Groups 5–8 had the same treatment regimen as Groups 1–4, but after the third injection the animals also received continuous dose of CP (2.5 mg/kg/day, i.p.) for 8 days. Group 9, as the positive control group, received sesame oil instead of Pr plus CP. Group 10, as the negative control group, received sesame oil instead of Pr. After the most effective dose of Pr was determined in Phase I, Groups 11–13 in Phase II received 10 mg/kg Pr plus either 0.25, 0.5, or 1 mg/kg, IM estradiol valerate every 5 days for four doses. After the third injection, they also received a continuous dose of CP for 8 days. The levels of blood urea nitrogen (BUN) and creatinine (Cr), kidney tissue damage score (KTDS), and kidney weight (KW) increased and body weight (BW) decreased in the positive control group (P < 0.05). Administration of Pr (10 mg/kg) plus CP decreased KTDS and BW loss and KW. Co-administration of ES/Pr at specific doses improved Cr, BUN, and KTDS; and resulted in reduced CP-induced nephrotoxicity. The results obtained suggest that the beneficial effect of Pr on CP-induced nephrotoxicity is dose-dependent. In addition, combination of Es/Pr with a specific dose decreased CP-induced nephrotoxicity.


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Indian Journal of Nephrology
Published by Wolters Kluwer - Medknow
Online since 20th Sept '07