Mechanisms of AFB1-induced neurotoxicity and protective effect of baicalin via inflammatory and antioxidant pathways in ducklings.

Aflatoxin B1 (AFB1) ranks among the most hazardous contaminants in the food chain. While its hepatotoxicity is well-documented, its potential threat to the nervous system and the underlying mechanisms remain a critical but understudied toxicological issue. This study was designed to systematically investigate the neurotoxic mechanisms of AFB1 and the protective intervention of baicalin, a natural flavonoid. Using an AFB1-intubated duckling model, we provided histological and TEM in vivo evidence that AFB1 can induce substantial damage in the cerebral cortex which demonstrated that AFB1 exposure caused severe histopathological and ultrastructural alterations. IHC quantification revealed AFB1 ∼5-40 fold activated the expression of NF-κB inflammatory, and led to the upregulation of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), and simultaneously compensatory elevation of Nrf2 expression, resulting in a sharp increase in oxidative stress. Importantly, pretreatment with baicalin dose-dependently ameliorated these injuries. It effectively inhibited NF-κB activation, attenuated neuroinflammation, and suppressed the Nrf2 signaling to combat oxidative damage. Our study provides novel evidence in an in vivo duckling model that baicalin exerts its neuroprotective effects in association with reciprocal alterations between the NF-κB and Nrf2 signaling axes. These findings not only fill a significant knowledge gap in AFB1-induced neurotoxicity but also provide a solid mechanistic foundation for developing baicalin as a natural-based detoxifying strategy to mitigate AFB1 contamination, thereby enhancing safety in animal husbandry and human food consumption.