Current hPSC-derived liver organoids for toxicity testing: Cytochrome P450 enzymes and drug metabolism

Toxicological Research, Journal Year: 2025, Volume and Issue: 41(2), P. 105 - 121

Published: Jan. 3, 2025

Language: Английский

NAM-based analysis of contaminant short-term organ toxicity in HepaRG and RPTEC/TERT1 cells

Toxicology, Journal Year: 2025, Volume and Issue: unknown, P. 154104 - 154104

Published: March 1, 2025

New Approach Methodologies (NAMs), including cell culture and multi-level omics analyses, are promising alternatives to animal testing. To become useable for risk assessment purposes they have be applicable different substance groups. One important group of substances is food contaminants, synthetic chemicals, such as perfluorooctanesulfonic acid (PFOS) perfluorooctanoic (PFOA), natural compounds, mycotoxins pyrrolizidine alkaloids. We tested five known contaminants affecting the liver and/or kidney - PFOS, PFOA, Aflatoxin B1 (AB1), lasiocarpine (Las), cadmium chloride using HepaRG RPTEC/TERT1 cells at non-cytotoxic concentrations 36 72h. Our NAM-based testing protocol included marker protein analysis cellular functions targeted transcriptomics followed by bioinformatics pathway analysis. The effects observed were compared with established in vivo results. Protein indicated various affected pathways cells, generally fewer cells. strongest transcriptional impact was noted Las This study demonstrated test protocol's applicability across substances, revealing significant differences between lines. while expressing renal-specific CYP enzymes, less suitable detecting requiring hepatic metabolic activation, like AB1. data supports concept specific toxicity, enabling prediction based on mechanism rather than target organ. Employing multiple techniques provided comprehensive insights into compound effects, steatosis, reactive oxygen species production DNA damage, highlighting potential an extended approach advancing toxicological assessments.

Language: Английский

The connection between Bayesian networks and adverse outcome pathway (AOP) networks and how to use it for predicting drug toxicity

Drug Discovery Today, Journal Year: 2025, Volume and Issue: unknown, P. 104350 - 104350

Published: April 1, 2025

Language: Английский