title: Quercetin offers cardioprotection against progression of experimental autoimmune myocarditis by suppression of oxidative and endoplasmic reticulum stress via endothelin-1/MAPK signalling.
abstract: 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.
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: 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: Ritsuo
authors.initials: R
authors.lastname: Tagaki
authors.forename: Makoto
authors.initials: M
authors.lastname: Kodama
authors.forename: Kenichi
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D024722:Cardiac Myosins; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045304:Cytochromes c / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D019332:Endothelin-1 / Q000378:metabolism*; D005355:Fibrosis; D006321:Heart / Q000187:drug effects; D020935:MAP Kinase Signaling System; D008297:Male; D009205:Myocarditis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D009206:Myocardium / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D053495:Osteopontin / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011794:Quercetin / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D015415:Biomarkers; D002316:Cardiotonic Agents; D019332:Endothelin-1; D053495:Osteopontin; D045304:Cytochromes c; D011794:Quercetin; D024722:Cardiac Myosins