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水飞蓟宾对 5-氟尿嘧啶诱导的大鼠卵巢毒性的治疗作用。

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

机构信息

Department of Chemistry and Chemical Processing Technologies, Macka Vocational School, Karadeniz Technical University, Trabzon, Turkiye.

Department of Medical Biochemistry, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkiye.

出版信息

J Biochem Mol Toxicol. 2023 Sep;37(9):e23408. doi: 10.1002/jbt.23408. Epub 2023 Jun 19.

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.

摘要

5-氟尿嘧啶(5-FU)是一种具有抗代谢物特性的氟嘧啶类抗肿瘤药物,其卵巢毒性是最重要的副作用之一。水飞蓟素(SLB)是一种在全球范围内使用的天然化合物,其抗氧化和抗炎特性尤为突出。本研究旨在通过生化和组织学分析评估 SLB 对 5-FU 诱导的卵巢毒性的治疗作用。这项研究在五个主要组进行,每组包含六只大鼠:对照组、SLB(5mg/kg)组、5-FU(100mg/kg)组、5-FU+SLB(2.5mg/kg)组和 5-FU+SLB(5mg/kg)组。采用分光光度法测定卵巢丙二醛(MDA)、总氧化态(TOS)、总抗氧化态(TAS)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、8-羟基-2'-脱氧鸟苷(8-OHdG)、肿瘤坏死因子-α(TNF-α)、髓过氧化物酶(MPO)和半胱天冬酶-3 的水平。采用苏木精和伊红染色法进行组织病理学检查。与对照组相比,5-FU 组 MDA、TOS、8-OHdG、TNF-α、MPO 和 caspase-3 水平显著升高,而 TAS、SOD 和 CAT 水平降低(p<0.05)。SLB 治疗以剂量依赖的方式显著恢复了这种损伤(p<0.05)。虽然与对照组相比,5-FU 组血管充血、水肿、出血、卵泡变性和白细胞浸润显著增加,但 SLB 治疗也显著恢复了这些损伤(p<0.05)。总之,SLB 通过降低氧化应激、炎症和细胞凋亡水平对 5-FU 诱导的卵巢损伤具有治疗作用。考虑到 SLB 作为一种辅助治疗药物来对抗化疗副作用的有用性可能是有帮助的。

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