Abstract | BACKGROUND/AIMS:
Anion channels such as chloride channel are known to participate in the regulation of a wide variety of cellular processes including development, differentiation, proliferation, apoptosis and regeneration. This study was designed to examine the effect of the non-selective anion channel blocker 4,4'-Diisothiocyanostilbene-2, 2'-disulfonic acid ( DIDS) on cardiac function and apoptosis using a rat model of ischemia/reperfusion (I/R). METHODS: Fifty male SD rats were randomly divided into the following groups including sham, I/R and I/R+DIDS (7, 14 or 28 mg/kg). In DIDS group, rats received DIDS treatment (4 ml/kg/hr) at the beginning of reperfusion for 2 hrs using a programmed micro-pump. Cardiac function was evaluated including left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP) as well as positive and negative maximal derivatives of left ventricular pressure (± dP/dt(max)). Myocardial infarct size was detected using the double staining with 2, 3, 5-triphenyl-2H-tetra-zolium chloride (TTC) and Evan's blue dye. DNA ladder, TUNEL assay, Bax and Bcl-2 protein levels were evaluated. Levels of ROS and Akt phosphorylation were detected. RESULTS: I/R injury compromised cardiac function as manifested by reduced LVSP and ± dP/dt(max) as well as pronounced apoptosis. I/R-induced cardiac anomalies were markedly ameliorated by DIDS. DIDS retarded I/R-induced myocardial infarct and apoptosis. In addition, DIDS ameliorated I/R-induced ROS production and Akt dephosphorylation in the heart. CONCLUSION: Taken together, our data revealed that DIDS may protect cardiomyocytes against I/R injury as evidenced by improved cardiac function, Bcl-2, Akt phosphorylation, and reduced myocardial apoptosis, Bax expression, ROS production and myocardial infarct size.
|
Authors | Xiaoming Wang, Yanan Cao, Mingzhi Shen, Bo Wang, Weiwei Zhang, Yan Liu, Xiaole He, Lin Wang, Yuesheng Xia, Mingge Ding, Xihui Xu, Jun Ren |
Journal | Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
(Cell Physiol Biochem)
Vol. 35
Issue 2
Pg. 676-88
( 2015)
ISSN: 1421-9778 [Electronic] Germany |
PMID | 25591913
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | © 2015 S. Karger AG, Basel. |
Chemical References |
- Chloride Channels
- Reactive Oxygen Species
- 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
|
Topics |
- 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
(administration & dosage, pharmacology)
- Animals
- Arterial Pressure
(drug effects)
- Chloride Channels
- Gene Expression Regulation
(drug effects)
- Male
- Myocardial Reperfusion Injury
(drug therapy, metabolism, physiopathology)
- Rats
- Rats, Sprague-Dawley
- Reactive Oxygen Species
(metabolism)
|