title: DIDS reduces ischemia/reperfusion-induced myocardial injury in rats.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Geriatrics, Xijing Hospital, the Fourth Military Medical University, Xi'an, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wang
authors.forename: Yanan
authors.initials: Y
authors.lastname: Cao
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Shen
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiaole
authors.initials: X
authors.lastname: He
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Yuesheng
authors.initials: Y
authors.lastname: Xia
authors.forename: Mingge
authors.initials: M
authors.lastname: Ding
authors.forename: Xihui
authors.initials: X
authors.lastname: Xu
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D018118:Chloride Channels; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D018118:Chloride Channels; D017382:Reactive Oxygen Species; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid