Caffeic acid phenethyl amide ameliorates ischemia/reperfusion injury and cardiac dysfunction in streptozotocin-induced diabetic rats

Cardiovascular Diabetology

Ming-Jai Su⁴  Yueh-Hsiung Kuo¹  Hsi-Lin Chiu²  Ying-Kang Tsai⁴  Wei-Lung Chang⁴  Wen-Pin Chen⁴  An-Sheng Lee³  Yi-Jin Ho⁴ 

[1] Department of Biotechnology, Asia University, Taichung 413, Taiwan;Department of Chemistry, National Taiwan University, Taipei 100, Taiwan;Department of Medicine, Mackay Medical College, New Taipei 252, Taiwan;Department of Pharmacology, College of Medicine, National Taiwan University, 11F, No. 1, Sec. 1, Jen-Ai Road, Taipei 10051, Taiwan

关键词: Caffeic acid phenethyl amide;    Ischemia/reperfusion injury;    Diabetes;   

Others  :  794260
DOI  :  10.1186/1475-2840-13-98

 received in 2014-04-04, accepted in 2014-05-26,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Ho et al.; licensee BioMed Central Ltd.

【 图 表 】

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