Lipid metabolism disorders contribute to hepatotoxicity of triclosan in mice

J Hazard Mater. 2020 Feb 15:384:121310. doi: 10.1016/j.jhazmat.2019.121310. Epub 2019 Sep 24.

Abstract

Previous in vivo exposure studies focused mainly on nuclear receptors involved in hepatotoxicity of triclosan (TCS). As liver plays a vital role in metabolic processes, dysregulations in lipid metabolism have been identified as potential drivers of pathogenesis. Investigation of changes in lipid metabolism might widen our understanding of toxicological effects as well as the underlying mechanism occurring in the liver. In this study, we comprehensively assessed the effect of TCS exposure on hepatic lipid metabolism in mice. Our results showed that TCS induced significant changes in hepatic free fatty acid pool by upregulation of fatty acid uptake and de novo fatty acid synthesis. Besides, hepatic levels of lipids, including acyl carnitine (AcCa), ceramide (Cer), triacylglycerols (TG), phosphatidylcholine (PC), lysophosphatidylcholine (LPC), phosphatidylethanolamine (PE) were also increased, together with upreguation of genes associated to TG synthesis, fatty acid oxidation and inflammation in TCS exposure group. These changes in lipid homeostasis could contribute to membrane instability, lipid accumulation, oxidative stress and inflammation. Our results suggested that TCS exposure could induce hepatic lipid metabolism disorders in mice, which would further contribute to the liver damage effects of TCS.

Keywords: Free fatty acid; Hepatotoxicity; Lipid metabolism disorder; Lipidomics; Triclosan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Infective Agents, Local / toxicity*
  • Chemical and Drug Induced Liver Injury / metabolism*
  • Fatty Acids, Nonesterified / biosynthesis
  • Fatty Acids, Nonesterified / metabolism
  • Lipid Metabolism / drug effects
  • Lipid Metabolism Disorders / metabolism*
  • Lipid Metabolism Disorders / pathology
  • Lipidomics
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oxidation-Reduction
  • Oxidative Stress
  • Triclosan / toxicity*
  • Triglycerides / biosynthesis
  • Up-Regulation / drug effects

Substances

  • Anti-Infective Agents, Local
  • Fatty Acids, Nonesterified
  • Triglycerides
  • Triclosan