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Beneficial effects of edaravone, a novel antioxidant, in rats with dilated cardiomyopathy
- Source :
- Journal of Cellular and Molecular Medicine
- Publication Year :
- 2012
- Publisher :
- Wiley, 2012.
-
Abstract
- Edaravone, a novel antioxidant, acts by trapping hydroxyl radicals, quenching active oxygen and so on. Its cardioprotective activity against experimental autoimmune myocarditis (EAM) was reported. Nevertheless, it remains to be determined whether edaravone protects against cardiac remodelling in dilated cardiomyopathy (DCM). The present study was undertaken to assess whether edaravone attenuates myocardial fibrosis, and examine the effect of edaravone on cardiac function in rats with DCM after EAM. Rat model of EAM was prepared by injection with porcine cardiac myosin 28 days after immunization, we administered edaravone intraperitoneally at 3 and 10 mg/kg/day to rats for 28 days. The results were compared with vehicle-treated rats with DCM. Cardiac function, by haemodynamic and echocardiographic study and histopathology were performed. Left ventricular (LV) expression of NADPH oxidase subunits (p47(phox), p67(phox), gp91(phox) and Nox4), fibrosis markers (TGF-β(1) and OPN), endoplasmic reticulum (ER) stress markers (GRP78 and GADD 153) and apoptosis markers (cytochrome C and caspase-3) were measured by Western blotting. Edaravone-treated DCM rats showed better cardiac function compared with those of the vehicle-treated rats. In addition, LV expressions of NADPH oxidase subunits levels were significantly down-regulated in edaravone-treated rats. Furthermore, the number of collagen-III positive cells in the myocardium of edaravone-treated rats was lower compared with those of the vehicle-treated rats. Our results suggest that edaravone ameliorated the progression of DCM by modulating oxidative and ER stress-mediated myocardial apoptosis and fibrosis.
- Subjects :
- Cardiomyopathy, Dilated
Male
Cardiac function curve
medicine.medical_specialty
Swine
Heart Ventricles
Blotting, Western
Endomyocardial fibrosis
Cardiomyopathy
Down-Regulation
Apoptosis
Antioxidants
Autoimmune Diseases
chemistry.chemical_compound
Fibrosis
Internal medicine
Edaravone
In Situ Nick-End Labeling
medicine
oxidative stress
Animals
NADPH oxidase
biology
Caspase 3
business.industry
fibrosis
Anti-Inflammatory Agents, Non-Steroidal
Cytochromes c
NADPH Oxidases
NOX4
Dilated cardiomyopathy
Original Articles
Cell Biology
Endomyocardial Fibrosis
Endoplasmic Reticulum Stress
medicine.disease
Rats
dilated cardiomyopathy
Myocarditis
Endocrinology
chemistry
Rats, Inbred Lew
cardiovascular system
biology.protein
Molecular Medicine
business
Cardiac Myosins
Antipyrine
Subjects
Details
- ISSN :
- 15821838
- Volume :
- 16
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular and Molecular Medicine
- Accession number :
- edsair.doi.dedup.....47aac735ed7dbea63706836d074903c4