Investigating the protective actions of D-pinitol against arsenic-induced toxicity in PC12 cells and the underlying mechanism

[Display omitted] •Arsenic induced cell death in PC12 cells via autophagy and apoptosis process.•D-pinitol rescued PC12 cells from arsenic-induced autophagy and apoptosis.•D-pinitol suppressed arsenic-induced inhibition of survival proteins in PC12 cells.•Arsenic upregulated p53, Bax, cytochrome c and LC3 expression which is repressed by D-pinitol co-exposure.•D-pinitol repressed the cellular arsenic intake into the PC12 cells. Arsenic is awfully toxic metalloid responsible for many human diseases all over the world. Contrastingly, D-pinitol is a naturally occurring bioactive dietary compound has antioxidant properties. The objective of this study is to elucidate the protective actions of D-pinitol on arsenic-induced cytotoxicity and explore its controlling role in biomolecular mechanisms in PC12 cells. Obtained results demonstrated that co-exposure of D-pinitol with arsenic increases cell viability, decreases DNA damage and protects PC12 cells from arsenic-induced cytotoxicity by increasing glutathione (GSH) level and glutathione reductase (GR). Protein expression of western blot analysis showed that co-exposure of D-pinitol and arsenic significantly inhibited arsenic-induced autophagy which further suppressed apoptosis through up-regulation of survival factors; mTOR, p-mTOR, Akt, p-Akt, NF-кB, Nrf2, ERK1, GR, Bcl-x and down-regulation of death factors; p53, Bax, cytochrome c, LC3, although arsenic regulated those factors negatively. These results of this study suggested that D-pinitol protects PC12 cells from arsenic-induced cytotoxicity.