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The therapeutic effect of silibinin against 5-fluorouracil-induced ovarian toxicity in rats
Authors:Elif Ayazoglu Demir  Ahmet Mentese  Hatice Kucuk  Nihal Turkmen Alemdar  Selim Demir
Affiliation:1. Department of Chemistry and Chemical Processing Technologies, Macka Vocational School, Karadeniz Technical University, Trabzon, Turkiye;2. Department of Medical Biochemistry, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkiye;3. Department of Pathology, Kanuni Training and Research Hospital, University of Health Sciences, Trabzon, Turkiye;4. Department of Medical Biochemistry, Graduate School of Health Sciences, Karadeniz Technical University, Trabzon, Turkiye;5. Department of Nutrition and Dietetics, Faculty of Health Sciences, Karadeniz Technical University, Trabzon, Turkiye
Abstract:5-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.
Keywords:5-fluorouracil  apoptosis  inflammation  ovary  oxidative stress  silibinin
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