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Safoora Mazaheri , Mehdi Nematbakhsh , Mehrnoosh Bahadorani , Zahra Pezeshki , Ardeshir Talebi , Ali‑Reza Ghannadi , Farzaneh Ashrafi

Abstract

Background: Cisplatin (cis‑diamminedichloroplatinum II (CDDP)) is an effective drug in cancer therapy to treat solid tumors. However, the drug is accompanied by nephrotoxicity. Previous reports indicated that estrogen has no protective role against CDDP‑induced nephrotoxicity, but the role of phytoestrogen as an estrogenic agent in plants is not determined yet. The major composition of fennel essential oil (FEO) is trans‑anethole that has estrogenic activity; so, we used FEO as a phytoestrogen source against CDDP‑induced nephrotoxicity. Materials and Methods: Fifty‑four ovariectomized Wistar rats were divided into seven groups. Groups 1-3 received different doses of FEO (250, 500, and 1000 mg/kg/day, respectively) for 10 days. Group 4 received saline for 10 days plus single dose of CDDP (7 mg/kg, intraperitoneally (ip)) at day 3. Groups 5-7 received FEO similar to groups 1-3, respectively; plus a single dose of CDDP (7 mg/kg, ip) on day 3. On day 10, the animals were sacrificed for histopathological studies. Results: The serum levels of blood urea nitrogen (BUN) and creatinine (Cr), kidney tissue damage score (KTDS), and kidney weight (KW) and body weight changes in CDDP‑treated groups increased significantly (P < 0.05). FEO did not reduce the levels of BUN and Cr, KTDS, and KW and body weight changes. Also, the serum and tissue levels of nitrite were not altered significantly by FEO. Conclusion: FEO, as a source of phytoestrogen, did not induce kidney damage. In addition, FEO similar to estrogen was not a nephroprotectant agent against CDDP‑induced nephrotoxicity.

Keywords

Cisplatin, fennel essential oil, nephrotoxicity, ovariectomized rats

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Zahra Pezeshki , Mehdi Nematbakhsh , Hamid Nasri , Ardeshir Talebi , Ali‑Asghar Pilehvarian , Tahereh Safari , Fatemeh Eshraghi‑Jazi , Maryam Haghighi , Farzaneh Ashrafi

Abstract

Cisplatin (CP) is an effective drug in cancer therapy to treat the solid tumors, but it is accompanied with nephrotoxicity. The protective effect of estrogen in cardiovascular diseases is well‑documented; but its nephron‑protective effect against CP‑induced nephrotoxicity is not completely understood. Materials and Methods: Thirty ovarectomized Wistar rats were divided in to five groups. Groups 1‑3 received different doses of estradiol valerate (0.5, 2.5 and 10 mg/kg/week) in sesame oil for 4 weeks, and at the end of week 3, a single dose of CP (7 mg/kg, intraperitoneal [IP]) was administrated. Group 4 (positive control) received the same regimen as group 1-3 without estradiol without vehicle. The negative control group (Group 5) received sesame oil during the study. The animals were sacrificed 1 week after CP injection for histopathological studies. Results: The serum level of blood urea nitrogen and creatinine, kidney tissue damage score (KTDS), kidney weight and percentage of body weight change in CP‑treated groups significantly increased (P < 0.05), however, there were no significant differences detected between the estrogen‑treated groups (Groups 1‑3) and the positive control group (Group 4). Although, estradiol administration enhanced the serum level of nitrite, it was not affected by CP. Finally, significant correlation between KTDS and kidney weight was detected (r2 = 0.63, P < 0.01). Conclusion: Estrogen is not nephron‑protective against CP‑induced nephrotoxicity. Moreover, it seems that the mechanism may be related to estrogen‑induced oxidative stress in the kidney, which may promote the nephrotoxicity.

Keywords

Cisplatin, estrogen, nephrotoxicity, ovarectomized rat

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