title: Caffeic acid phenethyl amide ameliorates ischemia/reperfusion injury and cardiac dysfunction in streptozotocin-induced diabetic rats.
abstract: BACKGROUND
  Caffeic acid phenethyl ester (CAPE) has been shown to protect the heart against ischemia/reperfusion (I/R) injury by various mechanisms including its antioxidant effect. In this study, we evaluated the protective effects of a CAPE analog with more structural stability in plasma, caffeic acid phenethyl amide (CAPA), on I/R injury in streptozotocin (STZ)-induced type 1 diabetic rats.
  
  
  METHODS
  Type 1 diabetes mellitus was induced in Sprague-Dawley rats by a single intravenous injection of 60 mg/kg STZ. To produce the I/R injury, the left anterior descending coronary artery was occluded for 45 minutes, followed by 2 hours of reperfusion. CAPA was pretreated intraperitoneally 30 minutes before reperfusion. An analog devoid of the antioxidant property of CAPA, dimethoxyl CAPA (dmCAPA), and a nitric oxide synthase (NOS) inhibitor (Nω-nitro-l-arginine methyl ester [l-NAME]) were used to evaluate the mechanism involved in the reduction of the infarct size following CAPA-treatment. Finally, the cardioprotective effect of chronic treatment of CAPA was analyzed in diabetic rats.
  
  
  RESULTS
  Compared to the control group, CAPA administration (3 and 15 mg/kg) significantly reduced the myocardial infarct size after I/R, while dmCAPA (15 mg/kg) had no cardioprotective effect. Interestingly, pretreatment with a NOS inhibitor, (L-NAME, 3 mg/kg) eliminated the effect of CAPA on myocardial infarction. Additionally, a 4-week CAPA treatment (1 mg/kg, orally, once daily) started 4 weeks after STZ-induction could effectively decrease the infarct size and ameliorate the cardiac dysfunction by pressure-volume loop analysis in STZ-induced diabetic animals.
  
  
  CONCLUSIONS
  CAPA, which is structurally similar to CAPE, exerts cardioprotective activity in I/R injury through its antioxidant property and by preserving nitric oxide levels. On the other hand, chronic CAPA treatment could also ameliorate cardiac dysfunction in diabetic animals.
authors.forename: Yi-Jin
authors.initials: YJ
authors.lastname: Ho
authors.forename: An-Sheng
authors.initials: AS
authors.lastname: Lee
authors.forename: Wen-Pin
authors.initials: WP
authors.lastname: Chen
authors.forename: Wei-Lung
authors.initials: WL
authors.lastname: Chang
authors.forename: Ying-Kang
authors.initials: YK
authors.lastname: Tsai
authors.forename: Hsi-Lin
authors.initials: HL
authors.lastname: Chiu
authors.forename: Yueh-Hsiung
authors.initials: YH
authors.lastname: Kuo
authors.affiliation: Department of Pharmacology, College of Medicine, National Taiwan University, 11F, No, 1, Sec, 1, Jen-Ai Road, Taipei 10051, Taiwan. mingja@ntu.edu.tw.
authors.forename: Ming-Jai
authors.initials: MJ
authors.lastname: Su
mesh_terms: D000818:Animals; D002109:Caffeic Acids / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000473:pathology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002109:Caffeic Acids; D007004:Hypoglycemic Agents; C584458:caffeic acid phenethyl amide