Perfluorooctanoic acid induces oxidative damage and mitochondrial dysfunction in pancreatic β-cells

Mol Med Rep. 2017 Jun;15(6):3871-3878. doi: 10.3892/mmr.2017.6452. Epub 2017 Apr 11.


Several environmental contaminants have been linked to the development of diabetes and increased diabetes‑associated mortality. Perfluorooctanoic acid (PFOA) is a widely used perfluoroalkane found in surfactants and lubricants, and in processing aids used in the production of polymers. Furthermore, PFOA has been detected in humans, wildlife and the environment. The present study investigated the toxic effects of PFOA on rat pancreatic β‑cell‑derived RIN‑m5F cells. Cell viability, apoptosis, reactive oxygen and nitrogen species, cytokine release and mitochondrial parameters, including membrane potential collapse, reduced adenosine triphosphate levels, cardiolipin peroxidation and cytochrome c release were assessed. PFOA significantly decreased RIN‑m5F cell viability and increased apoptosis. Exposure to PFOA increased the formation of reactive oxygen species, mitochondrial superoxide, nitric oxide and proinflammatory cytokines. Furthermore, PFOA induced mitochondrial membrane potential collapse and reduced adenosine triphosphate levels, cardiolipin peroxidation and cytochrome c release. These results indicate that PFOA is associated with the induction of apoptosis in RIN-m5F cells, and induces cytotoxicity via increased oxidative stress and mitochondrial dysfunction.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Apoptosis / drug effects
  • Caprylates / chemistry
  • Caprylates / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Cytochromes c / metabolism
  • Cytokines / metabolism
  • Fluorocarbons / chemistry
  • Fluorocarbons / pharmacology*
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism*
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / metabolism*
  • Nitric Oxide / metabolism
  • Oxidative Stress / drug effects*
  • Rats
  • Reactive Oxygen Species / metabolism


  • Caprylates
  • Cytokines
  • Fluorocarbons
  • Reactive Oxygen Species
  • Nitric Oxide
  • Adenosine Triphosphate
  • Cytochromes c
  • perfluorooctanoic acid