title: Antioxidative effect of luteolin pretreatment on simulated ischemia/reperfusion injury in cardiomyocyte and perfused rat heart.
abstract: OBJECTIVE
  To investigate the antioxidative effect and mechanism of luteolin on rat cardiomyocytes and isolated hearts followed by simulated ischemia/reperfusion (SI/R) injury.
  
  
  METHODS
  The left ventricular cardiomyocytes and the isolated hearts from adult rats were subjected to SI/R injury. The experiment groups included control, SI/R, luteolin + SI/R (Lut + SI/R), vitamin E (Vit E) + SI/R, and LY294002 + luteolin + SI/R (LY + Lut + SI/R) groups. Cell viability, shortening amplitude, lactate dehydrogenase (LDH) release, superoxide dismutase (SOD) activity, the production of reactive oxygen species (ROS) and malondialdehyde (MDA), expression levels of Akt, phosphorylated Akt, NOX2 (gp91phox), NOX2 mRNA, mitogen-activated protein kinase (p38 MAPK) and phosphorylated p38MAPK were all measured after 3-h simulated ischemia and 2-h simulated reperfusion procedure in cardiomyocytes. Vit E was used as a standard control. The contractile function of isolated hearts was further observed after they were subjected to 30-min global ischemia and 120-min reperfusion.
  
  
  RESULTS
  Pretreatment with 8-μmol/L luteolin substantially increased cell viability and shortening amplitude, while reducing evidence of oxidative stress-induced damage in the cells. In addition, the expression of NOX2, NOX2 mRNA and phosphorylation of p38MAPK were all downregulated. Furthermore, pretreatment with 40-μmol/L luteolin improved the recovery of myocardial contractile function following SI/R-induced injury, and luteolin markedly increased phosphorylation of Akt. However, all of the above effects were partially inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002.
  
  
  CONCLUSIONS
  Luteolin prevents SI/R-induced myocardial damage by reducing oxidative stress-induced injury in isolated rat hearts and cardiomyocytes, and the cardioprotection induced by luteolin was partially mediated by the PI3K/Akt pathway.
authors.affiliation: Institute of Cardiovascular Disease Research, Xuzhou Medical College, Xuzhou, Jiangsu Province, 221002, China.
authors.forename: Rui-Qu
authors.initials: RQ
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Disease Research, Xuzhou Medical College, Xuzhou, Jiangsu Province, 221002, China. dongyelichina@gmail.com.
authors.forename: Dong-Ye
authors.initials: DY
authors.lastname: Li
authors.affiliation: Institute of Cardiovascular Disease Research, Xuzhou Medical College, Xuzhou, Jiangsu Province, 221002, China.
authors.forename: Tong-da
authors.initials: TD
authors.lastname: Xu
authors.affiliation: Institute of Cardiovascular Disease Research, Xuzhou Medical College, Xuzhou, Jiangsu Province, 221002, China.
authors.forename: Sha-Sha
authors.initials: SS
authors.lastname: Zhu
authors.affiliation: Institute of Cardiovascular Disease Research, Xuzhou Medical College, Xuzhou, Jiangsu Province, 221002, China.
authors.forename: Huan-Jun
authors.initials: HJ
authors.lastname: Pan
authors.affiliation: Institute of Cardiovascular Disease Research, Xuzhou Medical College, Xuzhou, Jiangsu Province, 221002, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.affiliation: Institute of Cardiovascular Disease Research, Xuzhou Medical College, Xuzhou, Jiangsu Province, 221002, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Physiology, Xuzhou Medical College, Xuzhou, Jiangsu Province, 221002, China. sunh@xzmc.edu.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D047311:Luteolin / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008954:Models, Biological; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010477:Perfusion; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000975:Antioxidants; D003470:Culture Media; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D048051:p38 Mitogen-Activated Protein Kinases; D047311:Luteolin
keywords: cardiomyocyte; cardioprotection; ischemia/reperfusion; luteolin