The antioxidant edaravone attenuates ER-stress-mediated cardiac apoptosis and dysfunction in rats with autoimmune myocarditis

Hiroko Shimazaki, Kenichi Watanabe, Punniyakoti T. Veeraveedu, Meilei Harima, Rajarajan A. Thandavarayan, Wawaimuli Arozal, Hitoshi Tachikawa, Makoto Kodama, Yoshifusa Aizawa

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Experimental autoimmune myocarditis (EAM) is mediated by myocardial infiltration by myosin-specific T-cells secreting inflammatory cytokines. In this study, rat models of EAM were prepared by injection with porcine cardiac myosin. One week after immunization, edaravone was administered intraperitoneally at 3 or 10 mg/kg/day to rats for 2 weeks. Cardiac function was measured by haemodynamic and echocardiographic studies and TUNEL assay was performed. Left ventricular (LV) expression of NADPH oxidase sub-units (p47 phox and p67phox), pro-inflammatory cytokines (TNF-α), endoplasmic reticulum (ER) stress signalling proteins (GRP78, caspase-12 and GADD153) and mitogen-activated protein kinase (MAPK) family proteins (phospho-p38 MAPK and phospho-JNK) were measured by western blotting. Edaravone improved LV function in a dose-dependent manner. Central venous pressure was significantly low and LV ejection fraction and fractional shortening was significantly high in edaravone groups compared with those in the vehicle group. In addition, edaravone treatment down-regulated LV expressions of p47phox, TNF-α, GADD153, phospho-p38 MAPK and phospho-JNK. Furthermore, the LV expressions of p67phox, GRP78, caspase-12 and TUNEL-positive cells of rats with EAM treated with edaravone were significantly low compared with those of the vehicle group. These findings suggest that edaravone ameliorated the progression of EAM by inhibiting oxidative and ER stress and, subsequently, cardiac apoptosis.

Original languageEnglish (US)
Pages (from-to)1082-1090
Number of pages9
JournalFree Radical Research
Volume44
Issue number9
DOIs
StatePublished - Sep 2010

Keywords

  • Edaravone
  • apoptosis
  • endoplasmic reticulum stress
  • experimental autoimmune myocarditis
  • oxidative stress

ASJC Scopus subject areas

  • Biochemistry

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