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This review summarizes the existing information on the molecular pathways of AFB1\u2010induced hepatocellular damage and carcinogenesis through NF\u2010\u03baB\u2010mediated pathways, with an emphasis on the stepwise cascade from AFB1 bioactivation to chronic inflammation. When AFB1 is taken up by the hepatocellular membrane, it is metabolically bioactivated by cytochrome P450 (CYP450) enzymes to yield reactive intermediates (including AFB1\u20108,9\u2010epoxide) capable of directly covalently altering cellular macromolecules and producing reactive oxygen species (ROS). The accumulation of AFB1\u2010derived adducts and ROS leads to the activation of the inhibitor of \u03baB (I\u03baB) via IKK. This activation subsequently facilitates the phosphorylation and proteasomal degradation of I\u03baB, allowing NF\u2010\u03baB to translocate into the nucleus. Long\u2010term activation of NF\u2010\u03baB enhances the expression of pro\u2010inflammatory cytokines (IL\u20101\u03b2, TNF\u2010\u03b1), anti\u2010apoptotic factors, and proliferative stimuli, creating a chronic inflammatory microenvironment that permits hepatocarcinogenesis initiation. In addition, redox\u2010sensitive signaling cascades propagate NF\u2010\u03baB activation through AFB1\u2010induced oxidative stress. This review identifies some of the main contemporary issues, such as the definition of the upstream molecular sensors that mediate IKK\u2010IKB signaling under various conditions of exposure, mapping of downstream NF\u2010\u03baB effector programs, and the metabolic fate of AFB1 during prolonged pathway activation, which are still of primary concern in terms of translation. In addition, we thoroughly assessed emerging pharmacological interventions targeting the AFB1\u2010NF\u2010\u03baB axis, including natural polyphenols (curcumin and resveratrol), probiotics (Lactobacillus species), antioxidants (alpha\u2010lipoic acid), and novel candidates (phillygenin and copper\u2010albumin complexes). These interventions exert protective effects by inhibiting NF\u2010\u03baB, reducing oxidative stress, and controlling apoptosis. This review offers a mechanistic basis for explaining liver toxicity caused by AFB1 and prioritizes actionable therapeutic targets and future research directions to develop novel prevention and treatment options against aflatoxin\u2010induced hepatic pathologies.<\/jats:p>","DOI":"10.1002\/jbt.70889","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T06:36:08Z","timestamp":1778481368000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["NF\u2010\u03baB Signaling Pathway Activation in Aflatoxin B1\u2010Induced Hepatocellular Toxicity: Molecular Crosstalk With Oxidative Stress and I\u03baB Degradation"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8478-0140","authenticated-orcid":false,"given":"Salman","family":"Hosawi","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Sciences King Abdulaziz University Jeddah 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