Humans are exposed to heterocyclic amines (HCAs) from a wide range of sources, such as protein-rich thermally processed foods, cigarette smoke, contaminated river water, the atmosphere, soil, and forest fire ash. Although the carcinogenic and mutagenic hazards of HCAs have been widely studied, the potential neurotoxicity of these compounds still needs to be further elucidated. Here, we studied the neurotoxicity of the HCA 2-amino-3-methylimidazole[4,5-f]quinoline (IQ) in vivo by utilizing a zebrafish model. After 35 days of exposure at 8, 80, and 800 ng/mL, zebrafish exploratory behavior and locomotor activity were significantly inhibited, and light/dark preference behaviors were also disturbed. Moreover, the expression of Parkinson’s disease (PD)-related genes and proteins, dopamine-related genes, neuroplasticity-related genes, antioxidant enzyme genes and inflammatory cytokine genes in the zebrafish brain was significantly affected. The numbers of NeuN neurons in the midbrain were decreased in exposed zebrafish, while the numbers of apoptotic cells were increased. In summary, our research suggests that IQ is neurotoxic and significantly associated with PD and that long-term exposure to IQ may contribute to PD risk. This risk may be related to IQ-mediated effects on mitochondrial homeostasis and induction of oxidative stress and inflammation.

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