Differential Effects of CBZ-Induced Catalysis and Cytochrome Gene Expression in Three Dimensional Zebrafish Liver Cell Culture

Abstract

Two dimensional (2D) cell cultures have been the standard in vitro model for environmental safety research. However, it does not properly mimic in vivo system which hampered cellular proliferation and differentiation over an extended culture time and quickly lost its function. In this study, we constructed a new three dimensional (3D) zebrafish liver cell model that more closely mimics the in vivo micro-environment for pharmaceuticals metabolism studies. The magnetic levitation method was used to maintain the controlled and uniform 3D spheroids. These spheroids were then tested with carbamazepine (CBZ) treatment to determine the applicability of this assay in metabolism study. The results demonstrated that the 3D cell model is more resistant to CBZ over 2D cell culture and in vivo and 3D culture cells are noticeable in CYP1a1 activity and the concentration of carbamazepine-10,11-epoxide (CBZ-EP) than 2D cell culture. This 3D cell culture model will provide useful information toward the development of improved biomimetic organ functions for alternatives to animal testing in environmental contaminants.