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

Environ Toxicol Pharmacol. 2020 Feb:74:103302. doi: 10.1016/j.etap.2019.103302. Epub 2019 Nov 21.

Abstract

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.

Keywords: Apoptosis; Arsenic; Autophagy; Cytotoxicity; D-pinitol; Glutathione reductase.

MeSH terms

  • Animals
  • Arsenic / toxicity*
  • Autophagy
  • Cell Survival
  • Glutathione
  • Humans
  • Inositol / analogs & derivatives*
  • Inositol / pharmacology
  • PC12 Cells
  • Protective Agents / pharmacology*
  • Rats

Substances

  • Protective Agents
  • pinitol
  • Inositol
  • Glutathione
  • Arsenic