Abstract

Malathion is a highly neurotoxic organophosphate (OP) pesticide which is in wide use. It is known for its high toxicity to insects, which is caused by inhibition of acetylcholinesterase activity, and for being neurotoxic to humans and other mammals. The present study mainly focused on potential effect of 2,3’,5’,6-tetrahydroxy-trans-stilbene (gnetol) on malathion-induced neuronal cell death in N2a mouse neuroblastoma cells. Malathion activated lysosomal cathepsin B release, resulting in defective autophagy and induction of apoptotic cell death. Interestingly, gnetol (5, 10, and 20 μM) protected cells from apoptosis by regulating heart fatty acid binding protein 3 (hFABP3) and vascular endothelial growth factor (VEGF) expression, leading to improvements in the cellular and nuclear morphological changes induced by malathion. Gnetol induced autophagy by reducing lysosomal cathepsin B release as assessed by immunofluorescence staining, which ameliorated apoptotic cell death in N2a cells. Furthermore, the neurite outgrowth and the NGF level were upregulated by gnetol treatment. Taken together, gnetol, a resveratrol derivative, may protect neuronal cells against malathion-mediated apoptosis and potentiate neuritogenesis.

Graphical Abstract

Schematic representation of the proposed role of gnetol on lysosomal destabilization in malathion-induced apoptosis in N2a neuroblastoma cells

Keywords: Malathion; Autophagy; Gnetol; Phytochemicals; Neurodegenerative disease; Lysosomal destabilization