Apocynin exerts neuroprotective effects in fumonisin b1 induced neurotoxicity via attenuation of oxidative stress and apoptosis

The mycotoxin fumonisin b1 (Fb1) is produced by fusarium verticillioides , which commonly infects corn and other agricultural products. Fb1 found to be a source of vast range of toxic effects like hepatotoxicity, neurotoxicity and carcinogenicity in a number of animal species. However, the information available currently regarding neurotoxic effects exerted by Fb1 is scanty. Hence, the present study was aimed to evaluate the neurotoxic effects of Fb1 and the possible mechanisms of toxicity in mice and as well as the role of cytotoxic, oxidative stress and apoptosis in neuroblastoma (SH-SY5Y) cell line. In this context, the toxicity of Fb1 was examined in male albino mice. Apocynin with 25,50,100mg/kg b/wt was pretreated for 7 days oral administration. Fb1 6.75 mg/kg b/wt was injected subcutaneously for 5 days. A significant elevation of 5-HT was observed in mice treated with Fb1 in whole brain showed biogenic amines may reflect Fb1 neurotoxicity which was attenuated by pretreatment of apocynin. Fb1 treatment increased oxidative damage in the brain, as evidenced by a decrease in GSH level along with significant increases in ROS, lipid peroxidation, protein carbonyl. Apocynin supplementation significantly ameliorated these biological parameter changes. In addition, apocynin pretreatment normalized the degenerative changes in histology studies. The cytotoxicity of Fb1 was evaluated by MTT and LDH assay showed that, Fb1 induced dose-dependent cell death in SH-SY5Y cells and IC 50 value was determined as 150µM. Fb1 showed elevated reactive oxygen species, depolarized mitochondrial membrane potential and TEM observation showed vacuolation in SH-SY5Y cells. Further, apoptotic changes revealed in DAPI staining and DNA damage in comet assay. To overcome these toxicological effects, apocynin was pretreated followed by Fb1 exposure for 24 h. Pretreatment with apocynin resulted in significant increase in cell viability, restored membrane integrity, reactive oxygen species level was maintained and neutralized apoptotic changes. The protein expression CAT, GPx downregulated with Fb1 treatment and apoptotic markers caspase-3 and caspase-8 was upregulated. Pretretment with apocynin restored the antioxidant enzymes and overexpressed apocynin markers also altered. Collectively, these results suggest that ROS is the main upstream signal leading to increased Fb1 mediated neurotoxicity in mice and SH-SY5Y cells. Use of an antioxidant apocynin reversed the toxin-induced oxidative stress and apoptosis by its antioxidant potency.