葡萄种子提取物通过调节第一阶段解毒路径,防止了pyrifos诱导的老鼠肝中的毒性
Slim Ghrir1, Wassim Ben Abbes2, Adam Chourabi2
1Laboratory of Bioactive Substances, Center of Biotechnology of Borj-Cedria, BP 901, 2050, Hammam-Lif, Tunisia. slim_ghrir@hotmail.com.
葡萄种子提取物 (GSE) 在保护肝脏免受pyrifos (CPF) 中毒方面表现有前途. 通过调节基因表达和支持排毒途径,GSE治疗抵消了CPF诱导的肝损伤.
科学领域:
- 毒理学 毒理学 毒理学
- 肝病学 肝病学是一种肝病学.
- 药理学 药理学是指药理学的学科.
背景情况:
- pyrifos (CPF) 中毒是严重的公共卫生问题,没有有效的预防治疗.
- 由CPF诱导的肝毒性具有相当大的风险,需要探索保护策略.
研究的目的:
- 在大鼠模型中研究葡萄种子提取物 (GSE) 对pyrifos诱导的肝损伤的潜在保护作用.
- 阐明GSE对CPF毒性的肝保护作用背后的分子机制.
主要方法:
- 鼠每天服用单独的pyrifos (CPF) 或与葡萄种子提取物 (GSE) 结合,持续一周.
- 使用生物化学,分子和本病理学技术分析了肝脏组织.
- 用分子对接来研究GSE多与特定酶的相互作用.
主要成果:
- 暴露于CPF会导致严重的肝功能障碍,线粒体功能障碍,氧化应激和组织病理损伤.
- GSE治疗有效地预防了CPF诱导的肝毒性,恢复了代谢平衡和线粒体功能.
- GSE调节了细胞染色体P450 (CYP450) 基因表达,并通过抑制DNMT1作为表观遗传调节器,促进CYP2C6解毒路径.
结论:
- 葡萄种子提取物 (GSE) 在老鼠中显示出显著的肝脏保护作用,防止pyrifos (CPF) 毒性.
- GSE的机制涉及通过DNMT1抑制调节CYP450基因表达和表观遗传调节.
- GSE代表了一种有前途的治疗策略,用于减轻CPF中毒引起的肝损伤.
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