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BioMed Research International
Volume 2016 (2016), Article ID 4780872, 9 pages
http://dx.doi.org/10.1155/2016/4780872
Review Article

TAMH: A Useful In Vitro Model for Assessing Hepatotoxic Mechanisms

Pacific University School of Pharmacy, 222 SE 8th Avenue No. 451, Hillsboro, OR 97123, USA

Received 22 September 2016; Revised 10 November 2016; Accepted 24 November 2016

Academic Editor: Hemant Kumar

Copyright © 2016 Madison Davis and Brendan D. Stamper. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

In vitro models for hepatotoxicity can be useful tools to predict in vivo responses. In this review, we discuss the use of the transforming growth factor-α transgenic mouse hepatocyte (TAMH) cell line, which is an attractive model to study drug-induced liver injury due to its ability to retain a stable phenotype and express drug-metabolizing enzymes. Hepatotoxicity involves damage to the liver and is often associated with chemical exposure. Since the liver is a major site for drug metabolism, drug-induced liver injury is a serious health concern for certain agents. At the molecular level, various mechanisms may protect or harm the liver during drug-induced hepatocellular injury including signaling pathways and endogenous factors (e.g., Bcl-2, GSH, Nrf2, or MAPK). The interplay between these and other pathways in the hepatocyte can change upon drug or drug metabolite exposure leading to intracellular stress and eventually cell death and liver injury. This review focuses on mechanistic studies investigating drug-induced toxicity in the TAMH line and how alterations to hepatotoxic mechanisms in this model relate to the in vivo situation. The agents discussed herein include acetaminophen (APAP), tetrafluoroethylcysteine (TFEC), flutamide, PD0325901, lapatinib, and flupirtine.