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The antioxidant edaravone attenuates ER-stress-mediated cardiac apoptosis and dysfunction in rats with autoimmune myocarditis.
Free Radic Res. 2010 Sep; 44(9):1082-90.FR

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 p67(phox)), pro-inflammatory cytokines (TNF-alpha), 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 p47(phox), TNF-alpha, GADD153, phospho-p38 MAPK and phospho-JNK. Furthermore, the LV expressions of p67(phox), 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.

Authors+Show Affiliations

Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20815771

Citation

Shimazaki, Hiroko, et al. "The Antioxidant Edaravone Attenuates ER-stress-mediated Cardiac Apoptosis and Dysfunction in Rats With Autoimmune Myocarditis." Free Radical Research, vol. 44, no. 9, 2010, pp. 1082-90.
Shimazaki H, Watanabe K, Veeraveedu PT, et al. The antioxidant edaravone attenuates ER-stress-mediated cardiac apoptosis and dysfunction in rats with autoimmune myocarditis. Free Radic Res. 2010;44(9):1082-90.
Shimazaki, H., Watanabe, K., Veeraveedu, P. T., Harima, M., Thandavarayan, R. A., Arozal, W., Tachikawa, H., Kodama, M., & Aizawa, Y. (2010). The antioxidant edaravone attenuates ER-stress-mediated cardiac apoptosis and dysfunction in rats with autoimmune myocarditis. Free Radical Research, 44(9), 1082-90. https://doi.org/10.3109/10715762.2010.499904
Shimazaki H, et al. The Antioxidant Edaravone Attenuates ER-stress-mediated Cardiac Apoptosis and Dysfunction in Rats With Autoimmune Myocarditis. Free Radic Res. 2010;44(9):1082-90. PubMed PMID: 20815771.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The antioxidant edaravone attenuates ER-stress-mediated cardiac apoptosis and dysfunction in rats with autoimmune myocarditis. AU - Shimazaki,Hiroko, AU - Watanabe,Kenichi, AU - Veeraveedu,Punniyakoti T, AU - Harima,Meilei, AU - Thandavarayan,Rajarajan A, AU - Arozal,Wawaimuli, AU - Tachikawa,Hitoshi, AU - Kodama,Makoto, AU - Aizawa,Yoshifusa, PY - 2010/9/7/entrez PY - 2010/9/8/pubmed PY - 2011/1/19/medline SP - 1082 EP - 90 JF - Free radical research JO - Free Radic. Res. VL - 44 IS - 9 N2 - 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 p67(phox)), pro-inflammatory cytokines (TNF-alpha), 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 p47(phox), TNF-alpha, GADD153, phospho-p38 MAPK and phospho-JNK. Furthermore, the LV expressions of p67(phox), 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. SN - 1029-2470 UR - https://www.unboundmedicine.com/medline/citation/20815771/The_antioxidant_edaravone_attenuates_ER_stress_mediated_cardiac_apoptosis_and_dysfunction_in_rats_with_autoimmune_myocarditis_ L2 - http://www.tandfonline.com/doi/full/10.3109/10715762.2010.499904 DB - PRIME DP - Unbound Medicine ER -