Metformin in Contrast to Berberine Reversed Arsenic-Induced Oxidative Stress in Mitochondria From Rat Pancreas Probably via Sirt3-dependent Pathway

J Biochem Mol Toxicol. 2019 Sep;33(9):e22368. doi: 10.1002/jbt.22368. Epub 2019 Jul 23.


Exposure to arsenic has been linked to the development of type 2 diabetes though its mechanism of toxicity remains unresolved. In this study berberine (BBR) effects on arsenic-induced sirtuin 3 (Sirt3) modifications in isolated mitochondria from rat pancreas were evaluated and compared with metformin (MET). With arsenic, mitochondrial reactive oxygen species (ROS), oxidative stress, and insulin resistance were obtained higher than control. From our results and in the presence of arsenic trioxide, insulin resistance and Sirt3 levels were found to be predominantly elevated that could be the result of compensating mechanisms. Apparently, BBR and MET recruit both direct (as an antioxidant) and indirect mechanisms (Sirt3 content) to deal with arsenic trioxide toxicity. Metformin compared with BBR exhibited a less significant effect on ROS levels and since its direct antioxidant property is minor, depressed the ROS level mainly through the Sirt3 modification.

Keywords: Sirt3; arsenic; berberine; diabetes; metformin.

MeSH terms

  • Animals
  • Arsenic / pharmacology*
  • Berberine / pharmacology*
  • Hypoglycemic Agents / pharmacology*
  • Metformin / pharmacology*
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Oxidative Stress / drug effects*
  • Pancreas / drug effects*
  • Pancreas / metabolism*
  • Rats
  • Sirtuins / metabolism*


  • Hypoglycemic Agents
  • SIRT-3 protein, rat
  • Berberine
  • Metformin
  • Sirtuins
  • Arsenic