Long-term exposure to bisphenol A or S promotes glucose intolerance and changes hepatic mitochondrial metabolism in male Wistar rats

Food Chem Toxicol. 2019 Oct;132:110694. doi: 10.1016/j.fct.2019.110694. Epub 2019 Jul 22.

Abstract

The present study evaluates the effects of low-level long-term exposure to bisphenol A (BPA) and bisphenol S (BPS) on serum biochemical markers, glucose homeostasis, mitochondrial energy metabolism, biogenesis and dynamics, and redox status in livers of Wistar rats. While only the exposure to BPS induces a significant body mass gain after 21 weeks, both compounds alter serum lipid levels and lead to the development of glucose intolerance. Regarding mitochondrial metabolism, both bisphenols augment the electron entry by complex II relative to complex I in the mitochondrial respiratory chain (MRC), and reduce mitochondrial content; BPA reduces OXPHOS capacity and uncouples respiration (relative to maximal capacity of MRC) but promotes a significant increase in fatty acid oxidation. Either exposure to BPA or BPS leads to an increase in mitochondrial-derived reactive oxygen species, mainly at complex I. Additionally, BPA and BPS significantly upregulate the expression levels of dynamin-related protein 1 related to mitochondrial fission, while BPA downregulates the expression of proliferator-activated receptor gamma coactivator 1 alpha, a master regulator of mitochondrial biogenesis. In summary, our data shows that exposure to both compounds alters metabolic homeostasis and mitochondrial energy metabolism, providing new mechanisms by which BPA and BPS impair the mitochondrial metabolism.

Keywords: Bisphenol A; Bisphenol S; Mitochondria; Mitochondrial dysfunction; Reactive oxygen species; Toxicity.

MeSH terms

  • Animals
  • Benzhydryl Compounds / pharmacology*
  • Body Weight / drug effects
  • Energy Metabolism / drug effects
  • Glucose Tolerance Test*
  • Lipids / blood
  • Male
  • Mitochondria, Liver / drug effects*
  • Mitochondria, Liver / metabolism
  • Mitochondrial Dynamics / drug effects
  • Organ Size / drug effects
  • Oxidation-Reduction
  • Oxidative Phosphorylation / drug effects
  • Phenols / pharmacology*
  • Rats
  • Reactive Oxygen Species / metabolism
  • Sulfones / pharmacology*

Substances

  • Benzhydryl Compounds
  • Lipids
  • Phenols
  • Reactive Oxygen Species
  • Sulfones
  • bis(4-hydroxyphenyl)sulfone
  • bisphenol A