Key Laboratory for Deep Processing of Major Grain and Oil (The Chinese Ministry of Education), College of Food Science and Engineering, Wuhan Polytechnic University, Wuhan 430023, Hubei, China.
Key Laboratory of Animal Biological Products & Genetic Engineering, Ministry of Agriculture and Rural, Sinopharm Animal Health Corporation Ltd., Wuhan 430023, Hubei, China; State Key Laboratory of Novel Vaccines for Emerging Infectious Diseases, China National Biotec Group Company Limited, Beijing 100024, China.
Environ Int. 2024 Sep;191:108969. doi: 10.1016/j.envint.2024.108969. Epub 2024 Aug 22.
Emerging mycotoxins enniatins (ENNs) and beauvericin (BEA) pose potential health risks to humans through dietary exposure. However, research into their mechanisms of toxicity is limited, with a lack of comprehensive toxicological data. This study investigates from a hepatic lipid metabolism perspective, establishing a more precise and reliable 3D HepaRG hepatocyte spheroid model as an alternative for toxicity assessment. Utilizing physiological indices, histopathological analyses, lipidomics, and molecular docking techniques, it comprehensively elucidates the effects of ENNs and BEA on hepatic lipid homeostasis and their molecular toxicological mechanisms. Our findings indicate that ENNs and BEA impact cellular viability and biochemical functions, significantly altering lipid metabolism pathways, particularly those involving glycerophospholipids and sphingolipids. Molecular docking has demonstrated strong binding affinity of ENNs and BEA with key enzymes in lipid metabolism such as Peroxisome Proliferator-Activated Receptor α (PPARα) and Cytosolic Phospholipase A2 (cPLA2), revealing the mechanistic basis for their hepatotoxic effects and potential to impair liver function and human health. These insights enhance our understanding of the potential hepatotoxicity of such fungal toxins and lay a foundation for the assessment of their health risks.
新兴霉菌毒素恩镰菌素（ENNs）和 beauvericin（BEA）通过饮食暴露对人类健康构成潜在风险。然而，对其毒性机制的研究有限，缺乏全面的毒理学数据。本研究从肝脂质代谢的角度进行探讨，建立了更为精确和可靠的 3D HepaRG 肝细胞球体模型，作为毒性评估的替代方法。利用生理指标、组织病理学分析、脂质组学和分子对接技术，全面阐明了 ENNs 和 BEA 对肝脂质稳态的影响及其分子毒理学机制。我们的研究结果表明，ENNs 和 BEA 影响细胞活力和生化功能，显著改变脂质代谢途径，特别是涉及甘油磷脂和鞘脂的途径。分子对接表明，ENNs 和 BEA 与脂质代谢中的关键酶如过氧化物酶体增殖物激活受体α（PPARα）和胞质型磷脂酶 A2（cPLA2）具有较强的结合亲和力，揭示了它们肝毒性作用的机制基础以及对肝脏功能和人类健康造成损害的潜力。这些研究结果增进了我们对这些真菌毒素潜在肝毒性的理解，并为评估其健康风险奠定了基础。
