Three-dimensional (3D) HepaRG spheroid model with physiologically relevant xenobiotic metabolism competence and hepatocyte functionality for liver toxicity screening was written by Ramaiahgari, Sreenivasa C.;Waidyanatha, Suramya;Dixon, Darlene;De Vito, Michael J.;Paules, Richard S.;Ferguson, Stephen S.. And the article was included in Toxicological Sciences in 2017.Category: triazoles This article mentions the following:
Effective prediction of human responses to chem. and drug exposure is of critical importance in environmental toxicol. research and drug development. While significant progress has been made to address this challenge using in vitro liver models, these approaches often fail due to inadequate tissue model functionality. Herein, the authors describe the development, optimization, and characterization of a novel three-dimensional (3D) spheroid model using differentiated HepaRG cells that achieve and maintain physiol. relevant levels of xenobiotic metabolism (CYP1A2, CYP2B6, and CYP3A4/5). This in vitro model maintains a stable phenotype over multiple weeks in both 96- and 384-well formats, supports highly reproducible tissue-like architectures and models pharmacol.- and environmentally important hepatic receptor pathways (ie AhR, CAR, and PXR) analogous to primary human hepatocyte cultures. HepaRG spheroid cultures use 50-100× fewer cells than conventional two dimensional cultures, and enable the identification of metabolically activated toxicants. Spheroid size, time in culture and culture media composition were important factors affecting basal levels of xenobiotic metabolism and liver enzyme inducibility with activators of hepatic receptors AhR, CAR and PXR. Repeated exposure studies showed higher sensitivity than traditional 2D cultures in identifying compounds that cause liver injury and metabolism-dependent toxicity. This platform combines the well-documented impact of 3D culture configuration for improved tissue functionality and longevity with the requisite throughput and repeatability needed for year-over-year toxicol. screening. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Category: triazoles).
1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6) belongs to triazole derivatives. Many triazoles are versatile, biologically active compounds commonly used as fungicides and plant retardants. 1,2,3-Triazoles are usually prepared following (3+2) cycloaddition protocols. A common technique for unsubstituted triazoles is the Huisgen azide-alkyne 1,3-dipolar cycloaddition: a azide and an alkyne react at high temperature to form a ring. However, the Huisgen strategy produces a mixture of isomers (typically 1,4- and 1,5-disubstituted) when used to produce substituted triazoles.Category: triazoles
Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics