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 IC 50 value to be 150 µM of Fb1, which was protected by 100 µg of AP. The electron microscopy evaluated the Fb1-induced apoptotic conditions and its cell morphology 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.