title: Reducing the oxidative stress mediates the cardioprotection of bicyclol against ischemia-reperfusion injury in rats.
abstract: OBJECTIVE
  To investigate the beneficial effect of bicyclol on rat hearts subjected to ischemia-reperfusion (IR) injuries and its possible mechanism.
  
  
  METHODS
  Male Sprague-Dawley rats were intragastrically administered with bicyclol (25, 50 or 100 mg/(kg∙d)) for 3 d. Myocardial IR was produced by occlusion of the coronary artery for 1 h and reperfusion for 3 h. Left ventricular hemodynamics was continuously monitored. At the end of reperfusion, myocardial infarct was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and serum lactate dehydrogenase (LDH) level and myocardial superoxide dismutase (SOD) activity were determined by spectrophotometry. Isolated ventricular myocytes from adult rats were exposed to 60 min anoxia and 30 min reoxygenation to simulate IR injuries. After reperfusion, cell viability was determined with trypan blue; reactive oxygen species (ROS) and mitochondrial membrane potential of the cardiomyocytes were measured with the fluorescent probe. The mitochondrial permeability transition pore (mPTP) opening induced by Ca(2+) (200 μmol/L) was measured with the absorbance at 520 nm in the isolated myocardial mitochondria.
  
  
  RESULTS
  Low dose of bicyclol (25 mg/(kg∙d)) had no significant improving effect on all cardiac parameters, whereas pretreatment with high bicyclol markedly reduced the myocardial infarct and improved the left ventricular contractility in the myocardium exposed to IR (P<0.05). Medium dose of bicyclol (50 mg/(kg∙d)) markedly improved the myocardial contractility, left ventricular myocyte viability, and SOD activity, as well decreased infarct size, serum LDH level, ROS production, and mitochondrial membrane potential in rat myocardium exposed to IR. The reduction of ventricular myocyte viability in IR group was inhibited by pretreatment with 50 and 100 mg/(kg∙d) bicyclol (P<0.05 vs. IR), but not by 25 mg/(kg∙d) bicyclol. The opening of mPTP evoked by Ca(2+) was significantly inhibited by medium bicyclol.
  
  
  CONCLUSIONS
  Bicyclol exerts cardioprotection against IR injury, at least, via reducing oxidative stress and its subsequent mPTP opening.
authors.affiliation: Department of Physiology, School of Medicine, Zhejiang University, Hangzhou 310058, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Cui
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.forename: Ling-bo
authors.initials: LB
authors.lastname: Qian
authors.forename: Qin
authors.initials: Q
authors.lastname: Gao
authors.forename: Jue
authors.initials: J
authors.lastname: Wang
authors.forename: Meng
authors.initials: M
authors.lastname: Xue
authors.forename: Xiao-e
authors.initials: XE
authors.lastname: Lou
authors.forename: Iain C
authors.initials: IC
authors.lastname: Bruce
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xia
authors.forename: Hui-ping
authors.initials: HP
authors.lastname: Wang
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000008:administration & dosage*; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D002478:Cells, Cultured; D008297:Male; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D001713:Biphenyl Compounds; D002316:Cardiotonic Agents; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species; C477843:bicyclol