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

• Published in: Naunyn-Schmiedeberg's archives of pharmacology Vol. 392; no. 10; pp. 1225 - 1238
• Main Authors: Said, Riham S., Mantawy, Eman M., El-Demerdash, Ebtehal
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2019; Springer Nature B.V
• Subjects: Adenosine diphosphate; Apoptosis; Biomedical and Life Sciences; Biomedicine; Cancer therapies; Caspase; Caspase-3; Chemotherapy; Cisplatin; Cytochrome c; Females; Granulosa cells; Infertility; Inflammation; Inflammatory response; Laboratory animals; Neurosciences; Original Article; Ovaries; Pharmacology/Toxicology; Pharmacy; Platinum; Poly(ADP-ribose); Poly(ADP-ribose) polymerase; Radiation; Reproductive status; Resveratrol; Ribose; Toxicity; Tumor necrosis factor-TNF; Inflammation; Ovarian failure; Cisplatin; Resveratrol; Apoptosis
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/s00210-019-01662-x

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.