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.
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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.
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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).
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Said, R.S., Mantawy, E.M. & El-Demerdash, E. Mechanistic perspective of protective effects of resveratrol against cisplatin-induced ovarian injury in rats: emphasis on anti-inflammatory and anti-apoptotic effects. Naunyn-Schmiedeberg's Arch Pharmacol 392, 1225–1238 (2019). https://doi.org/10.1007/s00210-019-01662-x
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DOI: https://doi.org/10.1007/s00210-019-01662-x