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

Abstract

BackgroundCaffeic 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.MethodsType 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.ResultsCompared 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.ConclusionsCAPA, 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.

Caffeic Acid Phenethyl Ester inhibit Hepatic Fibrosis by Nitric Oxide Synthase and Cystathionine Gamma-Lyase in Rats

“…Under normal circumstances, eNOS is the main type of liver tissue NOS. It is secreted by the liver sinusoidal endothelial cells and acts on HSC through the paracrine to maintain its diastolic state, inhibit proliferation and migration, and to promote apoptosis of HSC [ 15 , 16 ]. iNOS is induced by liver toxins and some cytokines.…”

Diabetic Cardiomyopathy and Ischemic Heart Disease: Prevention and Therapy by Exercise and Conditioning

“…Hyperglycemia can activate the systemic and intra-cardiac renin-angiotensin system with consequent stimulation by angiotensin, of cardiac fibroblasts, and cardiac hypertrophy [24]. Further high levels of ROS in DCM can promote cellular apoptosis directly [25], especially in the presence of an attenuated antioxidant defense system [26][27][28] (Figure 2). The observed increase in pro-inflammatory cytokines in diabetic patients can recruit fibrogenic cells and activate the TGF-β/Smad signal, which in its own right can activate fibroblasts inducing the deposition of ECM [24].…”

Protective effect of Echinochrome against intrahepatic cholestasis induced by alpha-naphthylisothiocyanate in rats

“…Echinoderms have already been reported to contain pharmacologically active compounds with respect to antihistaminic, cytotoxicity (Riguera, 1997) and antiangiogenicity (Pandit et al, 2009). Sea urchins or urchins are small, spiky, spherical echinoderm animals (Ho et al, 2014). Echinochrome (Ech), or 7 (2) -ethyl-2, 3, 5, 6, 8-pentahydroxy-1, 4-naphthoquinone, is one of several spinochromes that occur as pigments in the shells and gonads of sea urchins (Lennikov et al, 2014).…”