Testing in vitro tools for the prediction of cholestatic liver injury induced by non-pharmaceutical chemicals.

Abstract

Bile acid accumulation and subsequent liver damage is a frequent adverse effect induced by drugs. Considerable efforts have therefore been focused on the introduction and characterization of tools that allow reliable prediction of this type of drug-induced liver injury. Among those are the cholestatic index and transcriptomic profiling, which are typically assessed in in vitro settings. The present study was set up to test the applicability of both tools to non-pharmaceutical compounds with cholestatic potential, including the industrial compound bis(2-ethylhexyl)phthalate, the cosmetic ingredients triclosan and octynoic acid, the herbicides paraquat and quizalofop-para-ethyl, and the food additives sunset yellow and tartrazine, in a human hepatoma cell culture model of cholestatic liver injury. The cholestatic index method showed cholestatic liability of sunset yellow, tartrazine and triclosan. Of those, tartrazine induced transcriptional changes reminiscent of the transcriptional profile of cholestatic drugs. Furthermore, a number of genes were found to be uniquely modulated by tartrazine, in accordance with the cholestatic drugs atazanavir, cyclosporin A and nefazodone, which may have potential as novel transcriptomic biomarkers of chemical-induced cholestatic liver injury. In conclusion, unambiguous identification of the non-pharmaceutical compounds tested in this study as inducers of cholestasis could not be achieved.

• Authors: Eva Gijbels, Lindsey Devisscher, Mathieu Vinken
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 152 Pg. 112165 (Jun 2021) ISSN: 1873-6351 [Electronic] England
• PMID: 33819548 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.

Chemical References

• Azo Compounds
• Triclosan
• 6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt
• Tartrazine

Topics

• Azo Compounds (toxicity)
• Cell Line, Tumor
• Chemical and Drug Induced Liver Injury (etiology, metabolism)
• Cholestasis (chemically induced, complications)
• Gene Expression (drug effects)
• Humans
• Tartrazine (toxicity)
• Transcriptome (drug effects)
• Triclosan (toxicity)