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L减轻双酚A诱导的Wistar大鼠卵巢功能障碍和炎症:生化、组织病理学、药代动力学及计算机模拟研究

L mitigates bisphenol A-induced ovarian dysfunction and inflammation in Wistar rats: biochemical, histopathological, pharmacokinetic, and in silico studies.

作者信息

Allagui Ikram, Sdayria Jazia, Athmouni Khaled, Zammel Nourhene, Guesmi Fatma, Saoudi Mongi, Giuffrè Angelo Maria, Allagui Mohamed Salah, Nahdi Saber, Harrath Abdel Halim

机构信息

Laboratory of Animal Ecophysiology, Faculty of Science, University of Sfax Tunisia, P.O. Box 95, CP 3000 Sfax, Tunisia.

Laboratory of Biotechnology and Biomonitoring of the Environment and Oasis Ecosystems, Faculty of Sciences of Gafsa, University Campus Sidi Ahmed Zarroug, University of Gafsa, 2112 Gafsa, Tunisia.

出版信息

3 Biotech. 2025 Jan;15(1):21. doi: 10.1007/s13205-024-04169-2. Epub 2024 Dec 23.

DOI:10.1007/s13205-024-04169-2
PMID:39720094
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11663833/
Abstract

The present study evaluated the antioxidant and anti-inflammatory properties of (CA) fruit extract against bisphenol A (BPA)-induced ovarian injury in female Wistar rats. The antioxidant activity was estimated by the total antioxidant capacity (TAC) and superoxide radical (NBT) content. For the in vivo analyses, 24 animals were divided into the following 4 groups: the control group; the BPA group (50 mg/kg BW BPA for 30 days); the BPA  + CA group (50 mg/kg BW BPA and 50 mg/kg BW CA); and the CA group (50 mg/kg BW CA). The in vitro results demonstrated that CA exhibited strong antioxidant activity and scavenged O•- radicals. . Pharmacokinetic properties were also explored, reflecting the physiological dynamics of the five active molecules (quercetin, catechin, kaempferol, rosmarinic acid, and naringenin). The in vivo findings revealed a significant increase in body weight associated with a significant increase in plasma C-reactive protein (CRP), proinflammatory cytokines (IL-1, IL-6, and TNF-α), and testosterone levels ( < 0.01). In addition, ovarian histological disruption was observed. However, co-administration of CA extract significantly improved ovarian histological integrity and attenuated inflammatory and androgenic disturbances. Moreover, in silico investigations showed that CA compounds interacted more strongly with the active sites of IL-1β, IL-6, or TNF-α. The best binding energy was observed between catechin (five H-bonds) and IL-1β and IL-6, at -6.0 and -6.1 kcal/mol, respectively, and between rosmarinic acid (four H-bonds) and TNF-α, at -6.4 kcal/mol. The present study supports the use of in the treatment of infertility for female polycystic ovary syndrome (PCOS) patients.

摘要

本研究评估了(CA)果实提取物对双酚A(BPA)诱导的雌性Wistar大鼠卵巢损伤的抗氧化和抗炎特性。通过总抗氧化能力(TAC)和超氧自由基(NBT)含量评估抗氧化活性。对于体内分析,将24只动物分为以下4组:对照组;BPA组(50 mg/kg体重BPA,持续30天);BPA + CA组(50 mg/kg体重BPA和50 mg/kg体重CA);以及CA组(50 mg/kg体重CA)。体外结果表明,CA表现出强大的抗氧化活性并清除O•-自由基。还探索了药代动力学特性,反映了五种活性分子(槲皮素、儿茶素、山奈酚、迷迭香酸和柚皮苷)的生理动态。体内研究结果显示体重显著增加,同时血浆C反应蛋白(CRP)、促炎细胞因子(IL-1、IL-6和TNF-α)以及睾酮水平显著升高(P < 0.01)。此外,观察到卵巢组织学破坏。然而,联合给予CA提取物显著改善了卵巢组织学完整性,并减轻了炎症和雄激素紊乱。此外,计算机模拟研究表明,CA化合物与IL-1β、IL-6或TNF-α的活性位点相互作用更强。儿茶素(五个氢键)与IL-1β和IL-6之间的最佳结合能分别为-6.0和-6.1 kcal/mol,迷迭香酸(四个氢键)与TNF-α之间的最佳结合能为-6.4 kcal/mol。本研究支持将其用于治疗女性多囊卵巢综合征(PCOS)患者的不孕症。

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