Back to Search
Start Over
Cordycepin, 3′-Deoxyadenosine, Prevents Rat Hearts from Ischemia/Reperfusion Injury Via Activation of Akt/GSK-3β/p70S6K Signaling Pathway and HO-1 Expression
- Source :
- Cardiovascular Toxicology. 14:1-9
- Publication Year :
- 2013
- Publisher :
- Springer Science and Business Media LLC, 2013.
-
Abstract
- Cordycepin (3'-deoxyadenosine) isolated from Cordyceps militaris, a species of the fungal genus Cordyceps, has been shown to exhibit many pharmacological functions, such as anticancer, anti-inflammatory, and antioxidant activities. In this study, we investigated the preventive role of cordycepin in ischemic/reperfusion (I/R) injury of isolated rat hearts and anesthetized rats. After Sprague-Dawley rats received cordycepin (3, 10, and 30 mg/kg) or control (0.5 % carboxyl methylcellulose) orally once a day for a week, hearts were isolated and mounted on Langendorff heart perfusion system. Isolated hearts were perfused with Krebs-Henseleit buffer for 15-min pre-ischemic stabilization period and subjected to 30-min global ischemia and 30-min reperfusion. Cordycepin administration (10 mg/kg, p.o.) significantly increased left ventricular developed pressure during the reperfusion period compared to that in the control group, but without any effect on coronary flow. Cordycepin (10 mg/kg, p.o.) significantly increased the phosphorylation of Akt/GSK-3β/p70S6K pathways, which are known to modulate multiple survival pathways. In addition, cordycepin decreased Bax and cleaved caspase-3 expression while increasing Bcl-2 expression, Bcl-2/Bax ratio, and heme oxygenase (HO-1) expression in isolated rat hearts. In anesthetized rats subjected to 30 min occlusion of left anterior descending coronary artery/2.5-h reperfusion, cordycepin (1, 3, and 10 mg/kg, i.v.) administered 15 min before the onset of ischemia dose-dependently decreased the infarct size in left ventricle. In conclusion, cordycepin could be an attractive therapeutic candidate with oral activity against I/R-associated heart diseases such as myocardial infarction.
- Subjects :
- Male
Langendorff heart
Cardiotonic Agents
Time Factors
Myocardial Infarction
Ischemia
Apoptosis
Myocardial Reperfusion Injury
Pharmacology
Toxicology
Ventricular Function, Left
Rats, Sprague-Dawley
Glycogen Synthase Kinase 3
chemistry.chemical_compound
Ventricular Pressure
Animals
Medicine
Phosphorylation
Molecular Biology
Protein kinase B
Cordyceps
Glycogen Synthase Kinase 3 beta
Deoxyadenosines
Dose-Response Relationship, Drug
biology
Cordycepin
business.industry
Myocardium
Ribosomal Protein S6 Kinases, 70-kDa
medicine.disease
biology.organism_classification
Rats
Enzyme Activation
Heme oxygenase
Disease Models, Animal
Oxidative Stress
Biochemistry
chemistry
Cytoprotection
Heme Oxygenase (Decyclizing)
Apoptosis Regulatory Proteins
Cardiology and Cardiovascular Medicine
business
Proto-Oncogene Proteins c-akt
Perfusion
Reperfusion injury
Signal Transduction
Subjects
Details
- ISSN :
- 15590259 and 15307905
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- Cardiovascular Toxicology
- Accession number :
- edsair.doi.dedup.....f1e5cc346e6b351051278326b603b8d1