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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 392, Issue 10, pp 1225–1238 | Cite as

Mechanistic perspective of protective effects of resveratrol against cisplatin-induced ovarian injury in rats: emphasis on anti-inflammatory and anti-apoptotic effects

  • Riham S. Said
  • Eman M. Mantawy
  • Ebtehal El-DemerdashEmail author
Original Article
  • 136 Downloads

Abstract

Chemotherapeutic platinum-containing drugs are widely used to treat a variety of cancer types; however, they cause ovarian failure and infertility. The aim of this study is to investigate the molecular mechanism underlying the potential protective effect of resveratrol against cisplatin-induced ovarian damage in a rat model. Female rats were given either cisplatin (6 mg/kg, i.p., once per week for two consecutive weeks) and/or resveratrol (10 mg/kg, orally for 17 days). Follicular development, ovarian function markers, as well as apoptotic and inflammatory markers were assessed 24 h after the last resveratrol dose. Resveratrol ameliorated the marked follicular loss and the significant reduction in anti-Müllerian hormone (AMH) level triggered by cisplatin. Mechanistically, cisplatin elicited a potent inflammatory response in ovarian tissue as evidenced by the elevated expression of tumor necrosis factor, nuclear factor kappa-B, and proinflammatory enzymes. Co-treatment with resveratrol inhibited the elevation in inflammatory mediators induced by cisplatin. Further, cisplatin switched on the apoptotic machinery in ovarian tissues via increasing the expression of both cytochrome c and caspase-3 which was reversed upon resveratrol co-treatment. Resveratrol also counteracts the upregulating poly(ADP-ribose) polymerase expression which could attribute to the inflammatory and apoptotic effects of cisplatin. Resveratrol protects the ovary from cisplatin-induced toxicity through preventing the loss of the AMH-secreting granulosa cells, diminishing PARP-1 expression, and downregulating the inflammatory and apoptotic events implicated in cisplatin toxicity.

Keywords

Cisplatin Ovarian failure Resveratrol Inflammation Apoptosis 

Notes

Author contributions

RS, EM, and EE conceived and designed the experiments. RS and EM performed the experiments. RS and EM analyzed the data. RS and EM contributed to the reagents/materials/analysis tools. RS, EM, and EE wrote the manuscript.

Compliance with ethical standards

All animals’ procedures in this study were conducted according to the Animal Ethics Committee, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt (Project no. 38).

Conflict of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Supplementary material

210_2019_1662_MOESM1_ESM.docx (15 kb)
ESM 1 (DOCX 14 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Drug Radiation Research, National Center for Radiation Research and TechnologyAtomic Energy AuthorityCairoEgypt
  2. 2.Department of Pharmacology and Toxicology, Faculty of PharmacyAin Shams UniversityAbasiaEgypt

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