M.J.L. and M.G.A. contributed equally to this work.
Liver Biology and Pathobiology
Microarray analysis in human hepatocytes suggests a mechanism for hepatotoxicity induced by trovafloxacin†
Article first published online: 23 DEC 2004
Copyright © 2004 American Association for the Study of Liver Diseases
Volume 41, Issue 1, pages 177–186, January 2005
How to Cite
Liguori, M. J., Anderson, M. G., Bukofzer, S., McKim, J., Pregenzer, J. F., Retief, J., Spear, B. B. and Waring, J. F. (2005), Microarray analysis in human hepatocytes suggests a mechanism for hepatotoxicity induced by trovafloxacin. Hepatology, 41: 177–186. doi: 10.1002/hep.20514
Conflict of interest: Nothing to report.
- Issue published online: 23 DEC 2004
- Article first published online: 23 DEC 2004
- Manuscript Accepted: 10 OCT 2004
- Manuscript Received: 26 FEB 2004
Idiosyncratic drug toxicity, defined as toxicity that is dose independent, host dependent, and usually cannot be predicted during preclinical or early phases of clinical trials, is a particularly confounding complication of drug development. An understanding of the mechanisms that lead to idiosyncratic liver toxicity would be extremely beneficial for the development of new compounds. We used microarray analysis on isolated human hepatocytes to understand the mechanisms underlying the idiosyncratic toxicity induced by trovafloxacin. Our results clearly distinguish trovafloxacin from other marketed quinolone agents and identify unique gene changes induced by trovafloxacin that are involved in mitochondrial damage, RNA processing, transcription, and inflammation that may suggest a mechanism for the hepatotoxicity induced by this agent. In conclusion, this work establishes the basis for future microarray analysis of new compounds to determine the presence of these expression changes and their usefulness in predicting idiosyncratic hepatotoxicity. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (HEPATOLOGY 2005;41:177–186.)