title: Beneficial effects of edaravone, a novel antioxidant, in rats with dilated cardiomyopathy.
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.
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, Japan.
authors.forename: Somasundaram
authors.initials: S
authors.lastname: Arumugam
authors.forename: Rajarajan A
authors.initials: RA
authors.lastname: Thandavarayan
authors.forename: Punniyakoti T
authors.initials: PT
authors.lastname: Veeraveedu
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Wawaimuli
authors.initials: W
authors.lastname: Arozal
authors.forename: Flori R
authors.initials: FR
authors.lastname: Sari
authors.forename: Vijayasree V
authors.initials: VV
authors.lastname: Giridharan
authors.forename: Vivian
authors.initials: V
authors.lastname: Soetikno
authors.forename: Suresh S
authors.initials: SS
authors.lastname: Palaniyandi
authors.forename: Meilei
authors.initials: M
authors.lastname: Harima
authors.forename: Kenji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Masaki
authors.initials: M
authors.lastname: Nagata
authors.forename: Makoto
authors.initials: M
authors.lastname: Kodama
authors.forename: Kenichi
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000473:pathology; D015153:Blotting, Western; D024722:Cardiac Myosins; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000473:pathology; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D000077553:Edaravone; D004719:Endomyocardial Fibrosis / Q000188:drug therapy / Q000473:pathology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D008297:Male; D009205:Myocarditis / Q000188:drug therapy / Q000473:pathology; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D013552:Swine
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D045304:Cytochromes c; D019255:NADPH Oxidases; C505410:Casp3 protein, rat; D053148:Caspase 3; D024722:Cardiac Myosins; D000077553:Edaravone; D000983:Antipyrine