Simultaneous gene expression signature of heart and peripheral blood mononuclear cells in astemizole-treated rats.
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.
Lee
Eun-Hee
EH
Korea Institute of Toxicology, 19 Shinseong-ro, Yuseong-gu, Daejeon 305-343, Republic of Korea.
Oh
Jung-Hwa
JH
Park
Han-Jin
HJ
Kim
Do-Geun
DG
Lee
Jong-Hwa
JH
Kim
Choong-Yong
CY
Kwon
Myung-Sang
MS
Yoon
Seokjoo
S
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
D039563:Histamine H1 Antagonists, Non-Sedating; D016589:Astemizole