Effects of N-n-butyl haloperidol iodide on myocardial ischemia/reperfusion injury and Egr-1 expression in rat.
We have previously shown that N-n-butyl haloperidol iodide (F2) derived from haloperidol reduces ischemia/reperfusion-induced myocardial injury by blocking intracellular Ca2+ overload. This study tested the hypothesis that cardio-protection with F2 is associated with an attenuation in the expression of early growth response gene 1 (Egr-1). In an in vivo rat model of 60 min coronary occlusion followed by 180 min of reperfusion, treatment with F2 significantly reduced myocardial injury evidenced by the reduction in release of plasma creatine kinase, myocardial creatine kinase isoenzyme and lactate dehydrogenase. In cultured neonatal rat cardiomyocytes of hypoxia for 3 h and reoxygenation for 1 h, F2 treatment attenuated necrotic and apoptotic cell death, as demonstrated by electron microscopy. Concomitant with cardio-protection by F2, the increased expression levels of Egr-1 mRNA and protein were significantly reduced in myocardial tissue and cultured cardiomyocytes as detected by reverse transcription-polymerase chain reaction, immunohistochemistry and immunocytochemistry. In conclusion, these results suggest that the protective effect of F2 on ischemia/reperfusion- or hypoxia/reoxygenation-induced myocardial injury might be partly mediated by downregulating Egr-1 expression.
Zhang
Yan-Mei
YM
Department of Pharmacology, Shantou University Medical College, Shantou 515041, China.
Shi
Gang-Gang
GG
Tang
Zhao
Z
Zheng
Jin-Hong
JH
Li
Wei-Qiu
WQ
Guo
Fu-Xiao
FX
Jia
Qiang-Yong
QY
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003402:Creatine Kinase / Q000097:blood; D052279:Creatine Kinase, MB Form / Q000097:blood; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis* / Q000378:metabolism; D006220:Haloperidol / Q000031:analogs & derivatives* / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000166:cytology; D012313:RNA / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology
D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; C482574:N-n-butyl haloperidol iodide; D012313:RNA; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D052279:Creatine Kinase, MB Form; D006220:Haloperidol; D002118:Calcium