Zhang Yu-Qian, Yao Xin, Zhu Hong-Mei, Lu Wei-Hong, Malhi Kanwar Kumar, Ullah Saleem Muhammad Asmat, Li Xue-Nan, Li Jin-Long
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P.R. China.
Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Northeast Agricultural University, Harbin 150030, P.R. China.
J Agric Food Chem. 2025 Jun 18;73(24):15113-15124. doi: 10.1021/acs.jafc.5c01732. Epub 2025 Jun 9.
Atrazine (ATZ), a widely used herbicide, induces neurotoxicity by disrupting microglial efferocytosis─a critical process for maintaining central nervous system homeostasis. Lycopene (LYC), a natural antioxidant, exhibits protective potential against pesticide-induced damage, yet its role in ATZ-impaired efferocytosis remains unexplored. Here, we demonstrate that LYC mitigates ATZ-induced hippocampal neuroinflammation and microglial dysfunction in mice. ATZ exposure triggered M1 polarization of microglia, apoptosis, and mitochondrial damage, accompanied by suppressed efferocytosis. However, LYC treatment significantly reduced pro-inflammatory cytokine levels (TNF-α, CD68), enhanced anti-inflammatory markers (IL-10, TGF-β), and restored mitochondrial integrity. Mechanistically, LYC upregulated MERTK expression (phagocytic receptor), facilitating microglial efferocytosis via enhanced IBA-1/MERTK colocalization. Molecular docking revealed a strong binding affinity between LYC and MERTK (-8.9 kcal/mol), suggesting direct interaction. These findings highlight MERTK as a novel target for LYC-mediated neuroprotection against ATZ toxicity, providing insights into potential dietary interventions for pesticide-associated neurological disorders.
莠去津（ATZ）是一种广泛使用的除草剂，它通过破坏小胶质细胞的吞噬作用来诱导神经毒性，而吞噬作用是维持中枢神经系统稳态的关键过程。番茄红素（LYC）是一种天然抗氧化剂，具有对抗农药诱导损伤的保护潜力，但其在ATZ损害的吞噬作用中的作用仍未得到探索。在此，我们证明LYC可减轻ATZ诱导的小鼠海马神经炎症和小胶质细胞功能障碍。暴露于ATZ会引发小胶质细胞的M1极化、凋亡和线粒体损伤，并伴有吞噬作用受到抑制。然而，LYC治疗显著降低了促炎细胞因子水平（TNF-α、CD68），增强了抗炎标志物（IL-10、TGF-β），并恢复了线粒体完整性。从机制上讲，LYC上调了MERTK表达（吞噬受体），通过增强IBA-1/MERTK共定位促进小胶质细胞的吞噬作用。分子对接显示LYC与MERTK之间具有很强的结合亲和力（-8.9千卡/摩尔），表明存在直接相互作用。这些发现突出了MERTK作为LYC介导的针对ATZ毒性的神经保护作用的新靶点，为农药相关神经疾病的潜在饮食干预提供了见解。
