title: Antihistamines modulate the integrin signaling pathway in h9c2 rat cardiomyocytes: Possible association with cardiotoxicity.
abstract: The identification of biomarkers for toxicity prediction is crucial for drug development and safety evaluation. The selective and specific biomarkers for antihistamines-induced cardiotoxicity is not well identified yet. In order to evaluate the mechanism of the life-threatening effects caused by antihistamines, we used DNA microarrays to analyze genomic profiles in H9C2 rat cardiomyocytes that were treated with antihistamines. The gene expression profiles from drug-treated cells revealed changes in the integrin signaling pathway, suggesting that cardiac arrhythmias induced by antihistamine treatment may be mediated by changes in integrin-mediated signaling. It has been reported that integrin plays a role in QT prolongation that may induce cardiac arrhythmia. These results indicate that the integrin-mediated signaling pathway induced by antihistamines is involved in various biological mechanisms that lead to cardiac QT prolongation. Therefore, we suggest that genomic profiling of antihistamine-treated cardiomyocytes has the potential to reveal the mechanism of adverse drug reactions, and this signal pathway is applicable to prediction of in vitro cardiotoxicity induced by antihistamines as a biomarker candidate.
authors.affiliation: National Institute of Drug and Safety Evaluation, Ministry of Food and Drug Safety, Osong-eup, Chungcheongbuk-do, Republic of Korea.
authors.forename: J S
authors.initials: JS
authors.lastname: Yun
authors.affiliation: National Institute of Drug and Safety Evaluation, Ministry of Food and Drug Safety, Osong-eup, Chungcheongbuk-do, Republic of Korea soyoukim@korea.kr.
authors.forename: S Y
authors.initials: SY
authors.lastname: Kim
mesh_terms: D000818:Animals; D002460:Cell Line; D020869:Gene Expression Profiling; D006321:Heart / Q000187:drug effects*; D006633:Histamine Antagonists / Q000494:pharmacology* / Q000633:toxicity; D016023:Integrins / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D006633:Histamine Antagonists; D016023:Integrins
keywords: QT/QTc; antihistamine; genomics; integrin