Open AccessBeneficial effects of edaravone, a novel antioxidant, in rats with dilated cardiomyopathy
Author(s) -
Arumugam Somasundaram,
Thandavarayan Rajarajan A.,
Veeraveedu Punniyakoti T.,
Nakamura Takashi,
Arozal Wawaimuli,
Sari Flori R.,
Giridharan Vijayasree V.,
Soetikno Vivian,
Palaniyandi Suresh S.,
Harima Meilei,
Suzuki Kenji,
Nagata Masaki,
Kodama Makoto,
Watanabe Kenichi
Publication year - 2012
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2012.01526.x
Subject(s) - edaravone , nadph oxidase , oxidative stress , nox4 , dilated cardiomyopathy , cardiac function curve , myocardial fibrosis , fibrosis , medicine , antioxidant , pharmacology , apoptosis , chemistry , tunel assay , endocrinology , biochemistry , heart failure
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 ( GRP 78 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.