Elmorsy Ekramy M, Abdelkader Afaf, Ali Nagah E, Elgendy Farouk S, Elbaghdady Heba Allah M, Mohammed Lina A, Anwer Hala M, Abu-Almakarem Amal S, Mohamed Mohamed E, Hinda Ioana A, Batrina Stefan, Botos Lucian, Imbrea Ilinca, Ibrahim Samah F, Shaban Enas, Abdeen Ahmed
Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt; Center for Health Research, Northern Border University, Arar 91431, Saudi Arabia.
Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Benha University, Benha 13518, Egypt.
Ecotoxicol Environ Saf. 2025 Aug 1;303:118777. doi: 10.1016/j.ecoenv.2025.118777.
Aflatoxins (AFB1) are harmful secondary metabolites generated by filamentous fungi with a profound hepatotoxic effect. Fucoxanthin (FX) is a flavonoid with a well-known cytoprotective action. Here, we evaluated the ability of FX to mitigate AFB1-triggered hepatotoxicity using the HepG2 cell line. Data revealed that AFB1 was cytotoxic to the hepatic cells in a concentration-dependent manner. AFB1 was shown to alter cytochrome P450 activities and its coding gene expression. It also caused genotoxicity to the liver cells with increased comet tail DNA parameters. Furthermore, AFB1 increased NF-κB/p65 and the proinflammatory cytokines accompanied by inhibition of cellular antioxidants, including CAT, SOD, NRF2, and HO-1 gene expressions, which leads to increased ROS generation and LPO in AFB1-treated cells. Besides, AFB1 increased the release of cytochrome c into the cytoplasm and enhanced the activities of caspases-3, -8, and -9. This was accompanied by an increased Bax/Bcl2 ratio and the activation of apoptosis pathways. FX (2.5-5 µM) was shown to mitigate AFB1-induced cytotoxicity to variable degrees. Molecular docking indicated the toxic effect of AFB1 as well as the preventive action of FX. These data suggest the potential therapeutic anti-inflammatory, antioxidant, and anti-apoptotic benefits of FX in preventing and treating AFB1 hepatotoxicity.
黄曲霉毒素（AFB1）是丝状真菌产生的有害次生代谢产物，具有深远的肝毒性作用。岩藻黄质（FX）是一种具有著名细胞保护作用的类黄酮。在此，我们使用HepG2细胞系评估了FX减轻AFB1引发的肝毒性的能力。数据显示，AFB1对肝细胞具有浓度依赖性细胞毒性。AFB1被证明会改变细胞色素P450活性及其编码基因表达。它还对肝细胞造成遗传毒性，彗星尾DNA参数增加。此外，AFB1增加了NF-κB/p65和促炎细胞因子，同时抑制了包括CAT、SOD、NRF2和HO-1基因表达在内的细胞抗氧化剂，这导致AFB1处理的细胞中ROS生成和LPO增加。此外，AFB1增加了细胞色素c释放到细胞质中，并增强了caspases-3、-8和-9的活性。这伴随着Bax/Bcl2比值增加和凋亡途径的激活。FX（2.5-5μM）被证明能不同程度地减轻AFB1诱导的细胞毒性。分子对接表明了AFB1的毒性作用以及FX的预防作用。这些数据表明FX在预防和治疗AFB1肝毒性方面具有潜在的治疗性抗炎、抗氧化和抗凋亡益处。
