Hyperoside Attenuates the Toxic Effect of Cisplatin on the Human Ovarian Granulosa Cells: Invitro Model Study

Cisplatin (cis-diamminedichloroplatinum II) (CDDP) is an FDA approved anticancer therapy that is commonly used in women’s cancer treatment protocols, such as breast, cervical, endometrial, and gestational trophoblastic cancers. Premature ovarian insufficiency/failure is a well-known long-term risk of chemotherapy including CDDP in women. Granulosa cells (GCs) are an essen-tial ovarian cell type that promotes oocyte growth and is crucial for ovarian reproductive function. Many types of chemotherapeutic agents, such as CDDP, could induce GCs apoptosis, which could result in ovarian failure. Hyperoside (HYP) is a flavonoid known for its beneficial phar-macological properties, including anti-inflammatory and antiapoptotic effects. Hence the current work aimed to evaluate the potential cytoprotective impact of HYP on CDDP-induced cytotoxicity in a human ovarian GCs cell line model. Forty-eight-hour exposure to 5-10µM CPPD resulted in reduction of GCs viability in a dose-dependent manner. HYP (40µM) was found to ameliorate this CPPD-induced effect on GCs viability. CPPD in a concentration-dependent way, dramatically reduced cellular ATP, mitochondrial activities, cellular progesterone, and estradiol secretion. It also increased oxidative stress markers, Akt kinase activity, cytochrome c levels, caspase -3.-8.-9, and Bax/Bcl2 ratio. These cytotoxic effects of CDDP on the treated GCs, were mitigated to varying degrees by HYP (40 µM). In conclusion, CDDP-induced cytotoxic effects on GCs seem to be the possible underlying cellular and molecular mechanisms of CDDP-induced ovarian insufficien-cy/failure. The study also demonstrated the therapeutic potential of HYP in mitigating CDDP-induced ovarian injury. Further studies are warranted to investigate the potential benefit of HYP as an adjuvant to CDDP treatment protocols to avoid adverse ovarian effects.