Fertility protective effect of taxifolin in cisplatin-induced ovarian damage
Ozyurt, R., Celik, N., Suleyman, Z., Cagiran, F., Kali, Z., Gurkan, N., Altindag, F., Bulut, S., Sarigul, C., Dinc, K., Suleyman, H.
- OBJECTIVE: The aim of our study was to investigate the protective effect of taxifo-lin on ovarian damage and reproductive dysfunc-tion created by cisplatin administration.MATERIALS AND METHODS: A total of 36 al-bino Wistar female adult rats were equally divided into 3 groups as cisplatin administered only (CIS), taxifolin+cisplatin (T+C) and healthy control group (HG). Taxifolin 50 mg/kg was administered orally by gavage in the T+C (n=12) group. In the HG (n=12) and CIS (n=12) groups, the same volume of distilled water as a solvent was orally administered. One hour after administration of taxifolin or distilled water, animals in the T+C and CIS groups were injected with cisplatin at a dose of 2.5 mg/kg in-traperitoneally. This procedure was repeated once a day for 14 days. Six animals from each group were sacrificed on day 15, and their ovaries were removed for histopathological and biochemical analysis. Ovarian tissue malondialdehyde (MDA), total Glutathione (tGSH), Nuclear Factor-Kappa B (NF-kB), Tumor Necrosis Factor-alpha (TNF-alpha), Inter-leukin 1 beta (IL-10), and Interleukin-6 (IL-6) levels were measured. The remaining animals (n=6 in each group) were kept in the laboratory with mature male rats for two months to breed.RESULTS: CIS administration led to an in-crease in inflammatory molecules and membrane lipid peroxidation products, and decreased the synthesis of antioxidant molecules. Compared to the CIS group, the ovarian tissue MDA, NF-kB, TNF-alpha, IL-10 and IL-6 levels were found to be sig-nificantly decreased in the T+C group (p<0.001 for all comparisons). On the other hand, the tGSH levels of the T+C group were significantly higher than the CIS group (p<0.001). Milder ovarian necrosis, fibrosis and follicle damage were detected in animals which were given taxifolin. Four out of the six rats (67%) treated with taxifolin gave birth within 27 days.CONCLUSIONS: We demonstrated, for the first time, that taxifolin ameliorates cisplatin-induced ovarian injury by decreasing MDA and proinflam-matory cytokines and increasing the antioxidant enzyme. The fact that more than half of the an-imals receiving taxifolin became pregnant sug-gests that the cytoprotective effect of taxifolin is strong enough to preserve fertility.
- Journal
- EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES
- Year
- 2022
- Volume
- 26
- Issue
- 19
- Pages
- 7195-7203
- ISSN
- 1128-3602
- WoS UID
- WOS:000877188200039