Triclocarban-induced responses of endogenous and xenobiotic metabolism in human hepatic cells: Toxicity assessment based on nontargeted metabolomics approach

Hongna Zhang, Yao Lu, Yanshan Liang, Lilong Jiang, Zongwei CAI*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Humans are frequently exposed to the antimicrobial triclocarban (TCC) due to its widespread use in consumer and personal care products. However, there is a paucity of research on potential hepatotoxic risks of TCC exposure. In this study, nontargeted metabolomics approach was applied to simultaneously investigate TCC-induced perturbation of endogenous metabolites and generation of xenobiotic metabolites in human hepatic cells. In normal hepatocytes, TCC exposure induced cellular redox imbalance as evidenced by the decrease of glutathione metabolism and overproduction of reactive oxygen species (ROS), resulting in DNA damage and lipid peroxidation. Defective oxidative phosphorylation and increased purine metabolism were two potential sources of elevated ROS. However, in cancerous hepatocytes, TCC exposure enhanced glutathione metabolism, glycolysis, and glutaminolysis, which contributed to the cellular homeostasis of redox and energy status, as well as the progression of liver cancer. As a xenobiotic, metabolic activation of TCC through phase I hydroxylation was observed. The hepatic cytotoxicity follows the order of 6-OH-TCC > 2'-OH-TCC > 3'-OH-TCC > DHC, with EC50 values of 2.42, 3.38, 7.38, and 24.8 μM, respectively, in 48 h-treated normal cells. This study improves current understanding of TCC-triggered hepatotoxicity, and provides novel perspectives for evaluating the interaction of environmental pollutants with biological systems.

Original languageEnglish
Article number122475
JournalJournal of Hazardous Materials
Volume392
DOIs
Publication statusPublished - 15 Jun 2020

Scopus Subject Areas

  • Environmental Engineering
  • Environmental Chemistry
  • Waste Management and Disposal
  • Pollution
  • Health, Toxicology and Mutagenesis

User-Defined Keywords

  • endogenous metabolism
  • hepatotoxicity
  • metabolomics
  • triclocarban
  • xenobiotic metabolism

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