Apocynin exerts neuroprotective effects in fumonisin b1–induced neurotoxicity via attenuation of oxidative stress and apoptosis in an animal model.

The Fusarium verticillioides produces a mycotoxin, that is, fumonisin b1 (Fb1),
which commonly infects corn and agricultural commodities. The Fb1 showed
hepatotoxicity, neurotoxicity, and carcinogenicity in animals. Hence, the present
investigation aimed to evaluate the effect of apocynin (AP) on Fb1-induced neurotoxic
effects and its mechanism in the mice model and cell line. The male
Balb/c mice, with the 6.75 mg/kg bwt of Fb1 were injected subcutaneously for
5 days to induce neurotoxicity. A significant elevation of serotonin (5-HT) was
observed in mice treated with Fb1 in the whole brain showing biogenic amines
may reflect Fb1 neurotoxicity, but the negatively regulated mechanisms were
attenuated by the pretreatment of AP. In addition, AP pretreatment normalized
apoptotic changes in histology and immunohistochemistry studies. In Western
blotting studies, apoptotic genes were upregulated and oxidative stress genes
were downregulated due to Fb1 treatment; while treating with AP, these gene
expressions were rectified. Further cell cytotoxicity was investigated by MTT and
lactate dehydrogenase (LDH) assays in SH-SY5Y cell line. MTT and LDH assays
indicated the IC50 value to be 150 μMof Fb1,whichwas protected by 100 μg of AP.
The electron microscopy evaluated the Fb1-induced apoptotic conditions and its
cellmorphology recovery by AP. These results suggest that nicotinamide adenine
dinucleotide phosphate hydrogen oxidase–mediated reactive oxygen species is
the primary upstream signal leading to increased Fb1-mediated neurotoxicity in
mice. The use of the antioxidant AP reversed the toxin-induced oxidative stress
and apoptosis by its antioxidant potency.