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

07:00 EST 5th March 2020 | BioPortfolio

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

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 EC 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.

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This article was published in the following journal.

Name: Journal of hazardous materials
ISSN: 1873-3336
Pages: 122475

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