التفاصيل البيبلوغرافية
| العنوان: |
Mechanistic Understanding of Idiosyncratic Drug-Induced Hepatotoxicity Using Co-Cultures of Hepatocytes and Macrophages. |
| المؤلفون: |
Villanueva-Badenas, Estela, Donato, M. Teresa, Tolosa, Laia |
| المصدر: |
Antioxidants; Jul2023, Vol. 12 Issue 7, p1315, 17p |
| مصطلحات موضوعية: |
DRUG side effects, LIVER cells, CELL culture, HEPATOTOXICOLOGY, MACROPHAGES, DRUG development |
| مستخلص: |
Hepatotoxicity or drug-induced liver injury (DILI) is a major safety issue in drug development as a primary reason for drug failure in clinical trials and the main cause for post-marketing regulatory measures like drug withdrawal. Idiosyncratic DILI (iDILI) is a patient-specific, multifactorial, and multicellular process that cannot be recapitulated in current in vitro models; thus, our major goal is to develop and fully characterize a co-culture system and to evaluate its suitability for predicting iDILI. For this purpose, we used human hepatoma HepG2 cells and macrophages differentiated from a monocyte cell line (THP-1) and established the appropriate co-culture conditions for mimicking an inflammatory environment. Then, mono-cultures and co-cultures were treated with model iDILI compounds (trovafloxacin, troglitazone) and their parent non-iDILI compounds (levofloxacin, rosiglitazone), and the effects on viability and the mechanisms implicated (i.e., oxidative stress induction) were analyzed. Our results show that co-culture systems including hepatocytes (HepG2) and other cell types (THP-1-derived macrophages) help to enhance the mechanistic understanding of iDILI, providing better hepatotoxicity predictions. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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