Aflatoxin B1 Induces Neurotoxicity through Reactive Oxygen Species Generation, DNA Damage, Apoptosis, and S-Phase Cell Cycle Arrest.

Aflatoxin B1 (AFB) is a mycotoxin widely distributed in a variety of food commodities and exhibits strong toxicity toward multiple tissues and organs. However, little is known about its neurotoxicity and the associated mechanism. In this study, we observed that brain integrity was markedly damaged in mice after intragastric administration of AFB (300 μg/kg/day for 30 days). The toxicity of AFB on neuronal cells and the underlying mechanisms were then investigated in the neuroblastoma cell line IMR-32. A cell viability assay showed that the IC50 values of AFB on IMR-32 cells were 6.18 μg/mL and 5.87 μg/mL after treatment for 24 h and 48 h, respectively. ROS levels in IMR-32 cells increased significantly in a time- and AFB concentration-dependent manner, which was associated with the upregulation of , and downregulation of , , and . Substantial DNA damage associated with the downregulation of , , and was also observed. Furthermore, AFB significantly induced S-phase arrest, which is associated with the upregulation of , , and . Finally, AFB induced apoptosis involving and . Taken together, AFB manifests a wide range of cytotoxicity on neuronal cells including ROS accumulation, DNA damage, S-phase arrest, and apoptosis-all of which are key factors for understanding the neurotoxicology of AFB.