The therapeutic effect of silibinin against 5‐fluorouracil‐induced ovarian toxicity in rats

Abstract

Abstract5‐Fluorouracil (5‐FU) is a fluoropyrimidine group antineoplastic drug with antimetabolite properties and ovotoxicity is one of the most important side effects. Silibinin (SLB) is a natural compound that is used worldwide and stands out with its antioxidant and anti‐inflammatory properties. The aim of this study was to evaluate the therapeutic effect of SLB in 5‐FU‐induced ovototoxicity using biochemical and histological analysis. This study was carried out in five main groups containing six rats in each group: control, SLB (5 mg/kg), 5‐FU (100 mg/kg), 5‐FU + SLB (2.5 mg/kg), and 5‐FU + SLB (5 mg/kg). The levels of ovarian malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), superoxide dismutase (SOD), catalase (CAT), 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG), tumor necrosis factor‐alpha (TNF‐α), myeloperoxidase (MPO), and caspase‐3 were determined using spectrophotometric methods. Hematoxylin and eosin staining method was employed for histopathological examination. MDA, TOS, 8‐OHdG, TNF‐α, MPO, and caspase‐3 levels in 5‐FU group were significantly increased compared with the control group, while the levels of TAS, SOD, and CAT were decreased (p < 0.05). SLB treatments statistically significantly restored this damage in a dose‐dependent manner (p < 0.05). Although vascular congestion, edema, hemorrhage, follicular degeneration, and leukocyte infiltration were significantly higher in the 5‐FU group compared with the control group, SLB treatments also statistically significantly restored these damages (p < 0.05). In conclusion, SLB has a therapeutic effect on the ovarian damage induced by 5‐FU via decreasing the levels of oxidative stress, inflammation, and apoptosis. It may be helpful to consider the usefulness of SLB as an adjuvant therapy to counteract the side effects of chemotherapy.

Gynotoxic Effects of Chemotherapy and Potential Protective Mechanisms

“…Moreover, the genes involved in apoptosis and the Wnt signaling pathway were expressed when the ovaries of young mice were cultured in vitro with 5-fluorouracil [ 53 ]. In a study of rats treated with 5-fluorouracil at a dose of 100 mg/kg, significantly higher vascular congestion, edema, follicular degeneration, and leukocyte infiltration were observed compared to those in the control group [ 135 ]. In another study on rats treated with 5-fluorouracil, increased levels of malondialdehyde (MDA), total oxidant status (TOS), and the oxidative stress index (OSI) were observed in the ovaries compared to the control group ( p = 0.011, p = 0.003, and p = 0.001, respectively) [ 136 ].…”