Long-Term Co-Exposure to Nanopolystyrene and Heterocyclic Aromatic Amines Induces Neurotoxicity in Zebrafish via the MAPK Pathway

Nanoplastics (NPs) are common hydrophobic contaminants in food packaging, readily interacting with other pollutants to produce severe unknown toxicity. Heterocyclic amines (HAAs) are carcinogenic hydrophobic byproducts commonly generated during the thermal processing of meat products. With the widespread adoption of takeout food, coexposure risks to NPs and HAAs are inevitable, yet studies on their combined contamination remain scarce. This study comprehensively evaluated the chronic toxic effects of coexposure to polystyrene nanoplastics (PS-NPs) and 9<i>H</i>-pyridine[3,4-<i>b</i>]indole (Norharman) on zebrafish (<i>Danio rerio</i>) through behavioral, histopathological, and transcriptomic analyses. Findings reveal that both PS-NPs and Norharman induce behavioral abnormalities with significant synergistic effects. This interaction likely disrupts the blood-brain barrier (BBB) by downregulating <i>Occludin</i> gene expression, triggering oxidative stress and apoptosis in the brain, and activating neuroinflammatory responses mediated by the MAPK signaling pathway. This study reveals the synergistic neurotoxic mechanism of coexisting food contaminants, providing a theoretical basis for assessing combined exposure risks.