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

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 t...

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Autores principales: Chang, Ching-Wei, Beland, Frederick A., Hines, Wade M., Fuscoe, James C., Han, Tao, Chen, James J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3155372/
https://www.ncbi.nlm.nih.gov/pubmed/21845099
http://dx.doi.org/10.3390/ijms12074609
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author Chang, Ching-Wei
Beland, Frederick A.
Hines, Wade M.
Fuscoe, James C.
Han, Tao
Chen, James J.
author_facet Chang, Ching-Wei
Beland, Frederick A.
Hines, Wade M.
Fuscoe, James C.
Han, Tao
Chen, James J.
author_sort Chang, Ching-Wei
collection PubMed
description 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.
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spelling pubmed-31553722011-08-15 Identification and Categorization of Liver Toxicity Markers Induced by a Related Pair of Drugs Chang, Ching-Wei Beland, Frederick A. Hines, Wade M. Fuscoe, James C. Han, Tao Chen, James J. Int J Mol Sci Article 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. Molecular Diversity Preservation International (MDPI) 2011-07-15 /pmc/articles/PMC3155372/ /pubmed/21845099 http://dx.doi.org/10.3390/ijms12074609 Text en © 2011 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0 This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Chang, Ching-Wei
Beland, Frederick A.
Hines, Wade M.
Fuscoe, James C.
Han, Tao
Chen, James J.
Identification and Categorization of Liver Toxicity Markers Induced by a Related Pair of Drugs
title Identification and Categorization of Liver Toxicity Markers Induced by a Related Pair of Drugs
title_full Identification and Categorization of Liver Toxicity Markers Induced by a Related Pair of Drugs
title_fullStr Identification and Categorization of Liver Toxicity Markers Induced by a Related Pair of Drugs
title_full_unstemmed Identification and Categorization of Liver Toxicity Markers Induced by a Related Pair of Drugs
title_short Identification and Categorization of Liver Toxicity Markers Induced by a Related Pair of Drugs
title_sort identification and categorization of liver toxicity markers induced by a related pair of drugs
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3155372/
https://www.ncbi.nlm.nih.gov/pubmed/21845099
http://dx.doi.org/10.3390/ijms12074609
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