Tetrabromobisphenol A induces cellular damages in pancreatic β-cells in vitro

J Environ Sci Health A Tox Hazard Subst Environ Eng. 2017 Jun 7;52(7):624-631. doi: 10.1080/10934529.2017.1294964. Epub 2017 Mar 16.

Abstract

Tetrabromobisphenol A (TBBPA) is a well-known organobrominated flame retardant. TBBPA has been detected in the environment. The roles played by environmental pollutants in increasing the prevalence of metabolic syndrome are attracting increasing concern. In the present work, we investigated the effects of TBBPA on rat pancreatic β-cells (the RIN-m5F cell line). RIN-m5F cells were incubated with different concentrations of TBBPA for 48 h, and cell viability and the extent of apoptosis were determined. We also measured the levels of inflammatory cytokines, reactive oxygen species (ROS), mitochondrial adenosine triphosphate (ATP), and cardiolipin, as well as the extent of cytochrome c release from mitochondria. TBBPA reduced the ATP level, induced cardiolipin peroxidation and cytochrome c release, and triggered apoptotic cell death. Moreover, TBBPA increased the levels of inflammatory cytokines (TNF-α and IL-1β), nitric oxide, intracellular ROS, and mitochondrial superoxide. Together, our results indicate that TBBPA damages pancreatic β-cells by triggering mitochondrial dysfunction and inducing apoptosis.

Keywords: Mitochondrial function; pancreatic β-cell-derived RIN-m5F cells; tetrabromobisphenol A.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Apoptosis / drug effects*
  • Cell Culture Techniques
  • Cell Line
  • Cell Survival / drug effects
  • Cytochromes c / metabolism
  • Cytokines / metabolism
  • Flame Retardants / toxicity*
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Nitric Oxide / metabolism
  • Polybrominated Biphenyls / toxicity*
  • Rats
  • Reactive Oxygen Species / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cytokines
  • Flame Retardants
  • Polybrominated Biphenyls
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Adenosine Triphosphate
  • Cytochromes c
  • tetrabromobisphenol A