title: Simultaneous gene expression signature of heart and peripheral blood mononuclear cells in astemizole-treated rats.
abstract: 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.
authors.affiliation: Korea Institute of Toxicology, 19 Shinseong-ro, Yuseong-gu, Daejeon 305-343, Republic of Korea.
authors.forename: Eun-Hee
authors.initials: EH
authors.lastname: Lee
authors.forename: Jung-Hwa
authors.initials: JH
authors.lastname: Oh
authors.forename: Han-Jin
authors.initials: HJ
authors.lastname: Park
authors.forename: Do-Geun
authors.initials: DG
authors.lastname: Kim
authors.forename: Jong-Hwa
authors.initials: JH
authors.lastname: Lee
authors.forename: Choong-Yong
authors.initials: CY
authors.lastname: Kim
authors.forename: Myung-Sang
authors.initials: MS
authors.lastname: Kwon
authors.forename: Seokjoo
authors.initials: S
authors.lastname: Yoon
mesh_terms: D000818:Animals; D016589:Astemizole / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D039563:Histamine H1 Antagonists, Non-Sedating / Q000633:toxicity*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D039563:Histamine H1 Antagonists, Non-Sedating; D016589:Astemizole