The modulatory effect of triclosan on the reversion of the activated phenotype of LX-2 hepatic stellate cells

J Biochem Mol Toxicol. 2020 Jan;34(1):e22413. doi: 10.1002/jbt.22413. Epub 2019 Nov 12.

Abstract

Hepatic diseases leading to fibrosis affect millions of individuals worldwide and are a major public health challenge. Although, there have been many advances in understanding hepatic fibrogenesis, an effective therapy remains elusive. Studies focus primarily on activation of the hepatic stellate cells (HSCs), the principal fibrogenic cells in the liver; however, fewer numbers of studies have examined molecular mechanisms that deactivate HSC, controlling the profibrogenic phenotype. In the present study, we evaluated cellular and molecular actions of the chemical triclosan (TCS) in reverting activated HSCs to a quiesced phenotype. We demonstrated that the inhibition of the enzyme fatty acid synthase by TCS in activated HSCs promotes survival of the cells and triggers cellular and molecular changes that promote cellular phenotypic reversion, offering potentially new therapeutic directions.

Keywords: alternative therapy; cellular metabolism; drug toxicity; hepatic fibrosis.

MeSH terms

  • Cell Line
  • Cell Survival / drug effects
  • Fatty Acid Synthases / antagonists & inhibitors
  • Fatty Acid Synthesis Inhibitors / pharmacology*
  • Hepatic Stellate Cells / cytology
  • Hepatic Stellate Cells / drug effects*
  • Humans
  • Triclosan / pharmacology*

Substances

  • Fatty Acid Synthesis Inhibitors
  • Triclosan
  • Fatty Acid Synthases