Quercetin offers cardioprotection against progression of experimental autoimmune myocarditis by suppression of oxidative and endoplasmic reticulum stress via endothelin-1/MAPK signalling

被引：63

作者：

Arumugam, Somasundaram ^{[1
]}

Thandavarayan, Rajarajan A. ^{[1
,2
]}

Arozal, Wawaimuli ^{[1
]}

Sari, Flori R. ^{[1
]}

Giridharan, Vijayasree V. ^{[2
]}

Soetikno, Vivian ^{[1
]}

Palaniyandi, Suresh S. ^{[3
]}

Harima, Meilei ^{[1
]}

Suzuki, Kenji ^{[4
]}

Nagata, Masaki ^{[5
]}

Tagaki, Ritsuo ^{[5
]}

Kodama, Makoto ^{[6
]}

Watanabe, Kenichi ^{[1
]}

机构：

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

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

[3] Henry Ford Hlth Syst, Div Hypertens & Vasc Res, Dept Internal Med, Detroit, MI USA

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

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

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

来源：

FREE RADICAL RESEARCH | 2012年 / 46卷 / 02期

关键词：

adverse cardiac remodelling; apoptosis; fibrosis; mitogen activated protein kinase signalling; oxidative stress; DILATED CARDIOMYOPATHY; FLAVONOID ANTIOXIDANT; CARDIAC APOPTOSIS; NITRIC-OXIDE; RATS; CELLS; PREVENTS; PROTECTS; DAMAGE; INHIBITION;

D O I：

10.3109/10715762.2011.647010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In order to test the hypothesis that treatment with quercetin at a dose of 10 mg/kg protects from the progression of experimental autoimmune myocarditis (EAM) to dilated cardiomyopathy (DCM), we have used the rat model of EAM induced by porcine cardiac myosin. Our results identified that the post-myocarditis rats suffered from elevated endoplasmic reticulum (ER) stress and adverse cardiac remodelling in the form of myocardial fibrosis, whereas the rats treated with quercetin have been protected from these changes as evidenced by the decreased myocardial levels of ER stress and fibrosis markers when compared with the vehicle-treated DCM rats. In addition, the myocardial dimensions and cardiac function were preserved significantly in the quercetin-treated rats in comparison with the DCM rats treated with vehicle alone. Interestingly, the rats treated with quercetin showed significant suppression of the myocardial endothelin-1 and also the mitogen activated protein kinases (MAPK) suggesting that the protection offered by quercetin treatment against progression of EAM involves the modulation of MAPK signalling cascade. Collectively, the present study provides data to support the role of quercetin in protecting the hearts of the rats with post myocarditis DCM.

引用

页码：154 / 163

页数：10

共 45 条

[1] Role of quercetin in modulating rat cardiomyocyte gene expression profile [J].

Angeloni, C. ;

Leoncini, E. ;

Malaguti, M. ;

Angelini, S. ;

Hrelia, P. ;

Hrelia, S. .

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2008, 294 (03) :H1233-H1243

[2] Role of quercetin and its in vivo metabolites in protecting H9c2 cells against oxidative stress [J].

Angeloni, C. ;

Spencer, J. P. E. ;

Leoncini, E. ;

Biagi, P. L. ;

Hrelia, S. .

BIOCHIMIE, 2007, 89 (01) :73-82

[3] Beneficial effects of angiotensin II receptor blocker, olmesartan, in limiting the cardiotoxic effect of daunorubicin in rats [J].

Arozal, Wawaimuli ;

Watanabe, Kenichi ;

Veeraveedu, Punniyakoti T. ;

Thandavarayan, Rajarajan A. ;

Harima, Meilei ;

Sukumaran, Vijayakumar ;

Suzuki, Kenji ;

Tachikawa, Hitoshi ;

Kodama, Makoto ;

Aizawa, Yoshifusa .

FREE RADICAL RESEARCH, 2010, 44 (11) :1369-1377

[4]

BELCH JJF, 1991, BRIT HEART J, V65, P245

[5] The quercetin paradox [J].

Boots, Agnes W. ;

Li, Hui ;

Schins, Roel P. F. ;

Duffin, Rodger ;

Heemskerk, Johan W. M. ;

Bast, Aalt ;

Haenen, Guido R. M. M. .

TOXICOLOGY AND APPLIED PHARMACOLOGY, 2007, 222 (01) :89-96

[6]

BORDER WA, 1994, NEW ENGL J MED, V331, P1286

[7] Protection against myocardial ischaemia/reperfusion injury by PPAR-α activation is related to production of nitric oxide and endothelin-1 [J].

Bulhak, A ;

Sjöquist, PO ;

Xu, CB ;

Edvinsson, L ;

Pernow, J .

BASIC RESEARCH IN CARDIOLOGY, 2006, 101 (03) :244-252

[8] The p38-MAPK inhibitor, SB203580, inhibits cardiac stress-activated protein kinases/c-Jun N-terminal kinases (SAPKs/JNKs) [J].

Clerk, A ;

Sugden, PH .

FEBS LETTERS, 1998, 426 (01) :93-96

[9] Quercetin, a flavonoid antioxidant, prevents and protects streptozotocin-induced oxidative stress and β-cell damage in rat pancreas [J].

Coskun, O ;

Kanter, M ;

Korkmaz, A ;

Oter, S .

PHARMACOLOGICAL RESEARCH, 2005, 51 (02) :117-123

[10]

HALLIWELL B, 1993, AM J CLIN NUTR, V57, P715

← 1 2 3 4 5 →