In vitrocell-based models of drug-induced hepatotoxicity screening: progress and limitation / Maryam Mirahmad, Reyhaneh Sabourian, Mohammad Mahdavi, Bagher Larijani, Maliheh Safavi

Abstract Drug-induced liver injury (DILI) is one of the major causes of post-approval withdrawal of therapeutics. As a result, there is an increasing need for accurate predictive in vitro assays that reliably detect hepatotoxic drug candidates while reducing drug discovery time, costs, and the number of animal experiments. In vitro hepatocyte-based research has led to an improved comprehension of the underlying mechanisms of chemical toxicity and can assist the prioritization of therapeutic choices with low hepatotoxicity risk. Therefore, several in vitro systems have been generated over the last few decades. This review aims to comprehensively present the development and validation of two-dimensional (2D) and three-dimensional (3D) culture approaches on hepatotoxicity screening of compounds and highlight the main factors affecting predictive power of experiments. To this end, we first summarize some of the recognized hepatotoxicity mechanisms and related assays used to appraise DILI mechanisms and then discuss the challenges and limitations of in vitro models.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:54

Enthalten in:

Drug metabolism reviews - 54(2022), 2, Seite 161-193

Sprache:

Englisch

Beteiligte Personen:

Mirahmad, Maryam [VerfasserIn]
Sabourian, Reyhaneh [VerfasserIn]
Mahdavi, Mohammad [VerfasserIn]
Larijani, Bagher [VerfasserIn]
Safavi, Maliheh [VerfasserIn]

Links:

FID Access [lizenzpflichtig]

Themen:

3D culture
Drug-induced liver injury
Hepatotoxicity
In vitroassay
Sensitivity analysis
Toxicity prediction

Umfang:

1 Online-Ressource (33 p)

doi:

10.1080/03602532.2022.2064487

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

KFL011123362