Neurotoxic effects of aflatoxin B1 on human astrocytes in vitro and on glial cell development in zebrafish in vivo
2020
Park, Sunwoo | Lee, Jin-Young | You, Seungkwon | Song, Gwonhwa | Lim, Whasun
Aflatoxin B1 is one of the well-known mycotoxins and mainly found in contaminated animal feed and various agricultural products inducing acute and chronic toxicology, tumor, and abnormal neural development. However, the effects of aflatoxin B1 on the human brain, especially on astrocytes, have not been studied in depth. In the present study, we studied the neurotoxic effects of aflatoxin B1, in vitro and in vivo. Aflatoxin B1 decreased the proliferation and stopped cell cycle progression at the sub G0/G1 stage with an increase in BAX, BAK, and cytochrome c proteins in human astrocytes. In addition, it increased the mitochondrial depolarization, oxidative stress, and calcium influx in both the cytosol and mitochondria. Surprisingly, inhibition of calcium overload in the cytosol and mitochondria, using calcium chelators and an inhibitor, partially rescued the proliferation of aflatoxin B1-treated astrocytes. Based on the toxicity assays using zebrafish models, aflatoxin B1 decreased the embryo survival rate with physiological changes and an increase in the caspase and tp53 genes. It also decreased the expression of gfap, mbp, and olig2 in the transgenic zebrafish embryo’s brain and axon. Our results revealed the specific mechanism of the neurotoxic effects of aflatoxin B1 on human astrocytes and zebrafish glial cells.
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