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Int. J. Mol. Sci. 2011, 12(7), 4609-4624; doi:10.3390/ijms12074609
Article

Identification and Categorization of Liver Toxicity Markers Induced by a Related Pair of Drugs

1
, 2
, 3
, 4
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 and 1,*
Received: 7 April 2011; in revised form: 25 May 2011 / Accepted: 12 July 2011 / Published: 15 July 2011
(This article belongs to the Special Issue Toxicogenomics)
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Abstract: Drug-induced liver injury (DILI) is the primary adverse event that results in the withdrawal of drugs from the market and a frequent reason for the failure of drug candidates in the pre-clinical or clinical phases of drug development. This paper presents an approach for identifying potential liver toxicity genomic biomarkers from a liver toxicity biomarker study involving the paired compounds entacapone (“non-liver toxic drug”) and tolcapone (“hepatotoxic drug”). Molecular analysis of the rat liver and plasma samples, combined with statistical analysis, revealed many similarities and differences between the in vivo biochemical effects of the two drugs. Six hundred and ninety-five genes and 61 pathways were selected based on the classification scheme. Of the 61 pathways, 5 were specific to treatment with tolcapone. Two of the 12 animals in the tolcapone group were found to have high ALT, AST, or TBIL levels. The gene Vars2 (valyl-tRNA synthetase 2) was identified in both animals and the pathway to which it belongs, the aminoacyl-tRNA biosynthesis pathway, was one of the three most significant tolcapone-specific pathways identified.
Keywords: liver toxicity; biomarker; genomic; personalized medicine; population heterogeneity; entacapone; tolcapone liver toxicity; biomarker; genomic; personalized medicine; population heterogeneity; entacapone; tolcapone
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.

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MDPI and ACS Style

Chang, C.-W.; Beland, F.A.; Hines, W.M.; Fuscoe, J.C.; Han, T.; Chen, J.J. Identification and Categorization of Liver Toxicity Markers Induced by a Related Pair of Drugs. Int. J. Mol. Sci. 2011, 12, 4609-4624.

AMA Style

Chang C-W, Beland FA, Hines WM, Fuscoe JC, Han T, Chen JJ. Identification and Categorization of Liver Toxicity Markers Induced by a Related Pair of Drugs. International Journal of Molecular Sciences. 2011; 12(7):4609-4624.

Chicago/Turabian Style

Chang, Ching-Wei; Beland, Frederick A.; Hines, Wade M.; Fuscoe, James C.; Han, Tao; Chen, James J. 2011. "Identification and Categorization of Liver Toxicity Markers Induced by a Related Pair of Drugs." Int. J. Mol. Sci. 12, no. 7: 4609-4624.


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