Simultaneous gene expression signature of heart and peripheral blood mononuclear cells in astemizole-treated rats
| Autor: | Jung-Hwa Oh, Seokjoo Yoon, Jong-Hwa Lee, Do-Geun Kim, Myung-Sang Kwon, Han-Jin Park, Eun-Hee Lee, Choong-Yong Kim |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Histamine H1 Antagonists Non-Sedating medicine.medical_specialty Health Toxicology and Mutagenesis Gene Expression Inflammation Toxicology medicine.disease_cause Peripheral blood mononuclear cell Rats Sprague-Dawley Internal medicine Heat shock protein medicine Animals Cardiotoxicity business.industry Gene Expression Profiling Myocardium Heart General Medicine Astemizole Rats Gene expression profiling Endocrinology Gene Expression Regulation Calcium ion homeostasis Leukocytes Mononuclear medicine.symptom business Oxidative stress medicine.drug |
| Zdroj: | Archives of Toxicology. 84:609-618 |
| ISSN: | 1432-0738 0340-5761 |
| DOI: | 10.1007/s00204-010-0529-5 |
| Popis: | We investigated the effects of astemizole, a second-generation antihistamine, on the heart and peripheral blood mononuclear cells (PBMCs) and identified the early markers of its cardiotoxicity using gene expression profiling. Astemizole causes torsades de pointes, which is a type of ventricular tachycardia. We administered astemizole (dosage: 20, 60 mg/kg) to male Sprague-Dawley rats, using an oral gavage. Cardiac tissue and PBMCs were collected from the rats 4 h after treatment. Gene expression profiles were obtained using an Affymetrix GeneChip. The most deregulated genes were associated with energy metabolism pathways and calcium ion homeostasis in the heart of astemizole-treated rats. The most altered genes in the PBMCs were those involved in developmental processes and cardiotoxicity. Genes related to the response to oxidative stress, reactive oxygen species, heat shock proteins, hypoxia, immunity, and inflammation were also deregulated in the heart and PBMCs. These data provide further insight into the genetic pathways affected by astemizole. In addition, the simultaneously deregulated genes identified herein may be further studied. It will be interesting to find out whether single genes or certain sets of these genes could finally serve as biomarkers for cardiotoxicity of astemizole or other similar antihistamine drugs. |
| Databáze: | OpenAIRE |
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