Investigation of the hepatotoxicity profile of chemical entities using Liverbeads® and WIF-B9 in vitro models (original) (raw)

The cytotoxicity proWle of various chemical entities was evaluated using two in vitro hepatocyte models. Liverbeads ® is a cryopreserved model consisting of primary hepatocytes entrapped in alginate beads. WIF-B9 is a hybrid cell line obtained by fusion of rat hepatoma (Fao) and human Wbroblasts (WI38). Various reference hepatotoxicants were tested and ranked according to their equivalent concentration 50 (EC50) for various biochemical endpoints (lactate dehydrogenase (LDH) release, 3-(4,5 dimethylthiazol 2yl)-2,5-diphenyl-2H tetrazolium bromure (MTT) activity, adenosine triphosphate (ATP) and glutathione (GSH) levels). The ranking obtained was comparable in both models and consistent with previously published results on hepatocyte monolayers. Ketoconazole, erythromycin estolate, retinoic acid, telithromycin and -naphthyl-isothiocyanate were among the most toxic chemicals in both models, with an EC50 < 200 M. Troleandomycin, spiramycin, erythromycin, diclofenac, taurodeoxycholate, warfarin, galactosamine, valproic acid and isoniazid were found to be less toxic. Few marked diVerences, potentially linked to metabolism pathways, were observed between EC50s in the two models for compounds such as cyclosporine A (10 and >831 M) and warfarin (5904 and 1489 M) in WIF-B9 and Liverbeads ® , respectively. The results obtained indicate that Liverbeads ® and WIF-B9 cells are reliable in vitro models to evaluate the hepatotoxic potential of a wide range of chemicals, irrespective of structure and pharmaceutical class.