Beneficial effects of edaravone, a novel antioxidant, in rats with dilated cardiomyopathy

被引：32

作者：

Arumugam, Somasundaram

Thandavarayan, Rajarajan A. ^{[2
]}

Veeraveedu, Punniyakoti T. ^{[3
]}

Nakamura, Takashi

Arozal, Wawaimuli

Sari, Flori R.

Giridharan, Vijayasree V. ^{[2
]}

Soetikno, Vivian

Palaniyandi, Suresh S. ^{[4
]}

Harima, Meilei

Suzuki, Kenji ^{[5
]}

Nagata, Masaki ^{[6
]}

Kodama, Makoto ^{[7
]}

Watanabe, Kenichi ^{[1
]}

机构：

[1] Niigata Univ Pharm & Appl Life Sci, Dept Clin Pharmacol, Fac Pharmaceut Sci, Akiha Ku, Niigata 9568603, Japan

[2] Niigata Univ Pharm & Appl Life Sci, Dept Funct & Analyt Food Sci, Niigata 9568603, Japan

[3] Osaka Univ, WPI Immunol Frontier Res Ctr, Osaka, Japan

[4] Stanford Univ, Sch Med, Dept Chem & Syst Biol, Stanford, CA 94305 USA

[5] Niigata Univ, Grad Sch Med & Dent Sci, Dept Gastroenterol, Niigata, Japan

[6] Niigata Univ, Grad Sch Med & Dent Sci, Dept Oral & Maxillofacial Surg, Niigata, Japan

[7] Niigata Univ, Grad Sch Med & Dent Sci, Dept Med 1, Niigata, Japan

来源：

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE | 2012年 / 16卷 / 09期

关键词：

edaravone; oxidative stress; endoplasmic reticulum stress; apoptosis; fibrosis; dilated cardiomyopathy; EXPERIMENTAL AUTOIMMUNE MYOCARDITIS; ENDOPLASMIC-RETICULUM STRESS; ACTIVATED PROTEIN-KINASE; GIANT-CELL MYOCARDITIS; OXIDATIVE STRESS; ANGIOTENSIN-II; CARDIAC APOPTOSIS; HEART-FAILURE; INFARCT SIZE; HYPERTROPHY;

D O I：

10.1111/j.1582-4934.2012.01526.x

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 (p47phox, p67phox, gp91phox and Nox4), fibrosis markers (TGF-beta 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.

引用

页码：2176 / 2185

页数：10

共 42 条

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