Fucoxanthin mitigates aflatoxin B1-triggered hepatotoxicity in HepG2 cells via modulation of oxidative stress, inflammatory cytokines, and caspases cascade

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. • FX reduces AFB1-induced oxidative stress and inflammation in HepG2 cells. • FX mitigates AFB1 hepatotoxicity by modulating NRF2 and CYP450 pathways. • AFB1 triggers apoptosis; FX counters via Bax/Bcl2 and caspase regulation. • FX enhances antioxidant enzymes (CAT, SOD) and reduces lipid peroxidation. • Molecular docking confirms FX's protective binding to key mRNA/proteins.