Antihistamines modulate the integrin signaling pathway in h9c2 rat cardiomyocytes: Possible association with cardiotoxicity. (August 2015)

• Record Type: Journal Article
• Authors: Yun, JS; Kim, SY
• Is Part Of: Human & experimental toxicology. Volume 34:Number 8(2015:Aug.)
• Page Start: 796
• Page End: 807
• Publication Date: 2015-08
• Subjects: QT/QTc -- antihistamine -- genomics -- integrin; Toxicology -- Periodicals; 615.9
• DOI: 10.1177/0960327114559988
• Languages: English
• ISSNs: 0960-3271

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.