{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:01:53Z","timestamp":1787068913657,"version":"build-2736575974"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T00:00:00Z","timestamp":1541030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate the effect of dimethyl fumarate (DMF) on Toll-like receptor (TLR) signalling pathway in isoproterenol (ISO)-induced cardiac hypertrophy in rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Sixty adult male Sprague-Dawley rats were randomly allocated into three groups. group I: rats received the vehicles only; group II: rats were treated with ISO (5 mg\/kg per day S.C.) to induce cardiac hypertrophy for 7 days; and group III: rats were given DMF (25 mg\/kg per 12 h P.O.) for 28 days, and at the last 7 days, they were treated with ISO (5 mg\/kg per day S.C.).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key findings<\/jats:title>\n                    <jats:p>Pretreatment with DMF decreased heart-to-body weight ratio, heart rate and blood pressure and improved the electrocardiographic patterns when compared with ISO group. DMF exhibited cardioprotective effect as evidenced by the reduction in cardiac troponin I, creatine kinase-MB and atrial natriuretic peptide levels. Moreover, DMF alleviated the changed oxidative stress and inflammatory biochemical markers through its anti-inflammatory and antioxidant effects. DMF interfered with TLR signalling pathway, evidenced by decreased levels of the TLR adaptor protein MyD88 and p-ERK1\/2 and increased p-Akt level.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Dimethyl fumarate exerted cardioprotective effect against ISO-induced cardiac hypertrophy. This effect is suggested to be through interfering with TLR signalling pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jphp.13000","type":"journal-article","created":{"date-parts":[[2018,9,2]],"date-time":"2018-09-02T23:08:52Z","timestamp":1535929732000},"page":"1521-1530","source":"Crossref","is-referenced-by-count":17,"title":["Dimethyl fumarate interferes with MyD88-dependent toll-like receptor signalling pathway in isoproterenol-induced cardiac hypertrophy model"],"prefix":"10.1093","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6393-209X","authenticated-orcid":false,"given":"Asmaa A","family":"Ahmed","sequence":"first","affiliation":[{"name":"Pharmacology and Toxicology Department, Faculty of Pharmacy, Helwan University , Ein Helwan,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amany A E","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Department, Faculty of Pharmacy, Helwan University , Ein Helwan,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Engy M","family":"El Morsy","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Department, Faculty of Pharmacy, Helwan University , Ein Helwan,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahira","family":"Nofal","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Department, Faculty of Pharmacy, Helwan University , Ein Helwan,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,11,1]]},"reference":[{"key":"2024103012313231500_jphp13000-cit-0001","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1172\/JCI28884","article-title":"Cardiac hypertrophy: stressing out the heart","volume":"116","author":"Tardiff","year":"2006","journal-title":"J Clin Invest"},{"key":"2024103012313231500_jphp13000-cit-0002","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.yjmcc.2016.06.001","article-title":"Physiological and pathological cardiac hypertrophy","volume":"97","author":"Shimizu","year":"2016","journal-title":"J Mol Cell Cardiol"},{"key":"2024103012313231500_jphp13000-cit-0003","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.pharmthera.2010.04.005","article-title":"Molecular distinction between physiological and pathological cardiac hypertrophy: experimental findings and therapeutic strategies","volume":"128","author":"Bernardo","year":"2010","journal-title":"Pharmacol Ther"},{"key":"2024103012313231500_jphp13000-cit-0004","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1056\/NEJM199005313222203","article-title":"Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study","volume":"322","author":"Levy","year":"1990","journal-title":"N Engl J Med"},{"key":"2024103012313231500_jphp13000-cit-0005","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1157\/13087900","article-title":"Cardiac hypertrophy: molecular and cellular events","volume":"59","author":"Carre\u00f1o","year":"2006","journal-title":"Rev Esp Cardiol (Engl Ed)"},{"key":"2024103012313231500_jphp13000-cit-0006","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4081\/hi.2010.e7","article-title":"Carbamazepine alone and in combination with doxycycline attenuates isoproterenol-induced cardiac hypertrophy","volume":"5","author":"Errami","year":"2010","journal-title":"Heart Int"},{"key":"2024103012313231500_jphp13000-cit-0007","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1186\/1479-5876-11-130","article-title":"A proteomic view of isoproterenol induced cardiac hypertrophy: prohibitin identified as a potential biomarker in rats","volume":"11","author":"Chowdhury","year":"2013","journal-title":"J Transl Med"},{"key":"2024103012313231500_jphp13000-cit-0008","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1007\/s10741-007-9007-4","article-title":"Cardiac hypertrophy induced by sustained \u03b2-adrenoreceptor activation: pathophysiological aspects","volume":"12","author":"Osadchii","year":"2007","journal-title":"Heart Fail Rev"},{"key":"2024103012313231500_jphp13000-cit-0009","doi-asserted-by":"crossref","first-page":"2728","DOI":"10.1111\/jcmm.12659","article-title":"Up-regulated TLR4 in cardiomyocytes exacerbates heart failure after long term myocardial infarction","volume":"19","author":"Liu","year":"2015","journal-title":"J Cell Mol Med"},{"key":"2024103012313231500_jphp13000-cit-0010","doi-asserted-by":"crossref","first-page":"RA100","DOI":"10.12659\/MSM.881709","article-title":"Toll-like receptor and its roles in myocardial ischemic\/reperfusion injury","volume":"17","author":"Fang","year":"2011","journal-title":"Med Sci Monit"},{"key":"2024103012313231500_jphp13000-cit-0011","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.cardiores.2005.08.007","article-title":"TOLL-erating cardiac hypertrophy following pressure overload","volume":"68","author":"Van Oort","year":"2005","journal-title":"Cardiovasc Res"},{"key":"2024103012313231500_jphp13000-cit-0012","doi-asserted-by":"crossref","first-page":"e2234","DOI":"10.1038\/cddis.2016.140","article-title":"The emerging role of Toll-like receptor 4 in myocardial inflammation","volume":"7","author":"Yang","year":"2016","journal-title":"Cell Death Dis"},{"key":"2024103012313231500_jphp13000-cit-0013","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s40591-015-0041-7","article-title":"Cross talk of the first-line defense TLRs with PI3K\/Akt pathway, in preconditioning therapeutic approach","volume":"3","author":"Pourrajab","year":"2015","journal-title":"Mol Cell Ther"},{"key":"2024103012313231500_jphp13000-cit-0014","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1038\/ncpcardio0938","article-title":"Mechanisms of disease: Toll-like receptors in cardiovascular disease","volume":"4","author":"Frantz","year":"2007","journal-title":"Nat Clin Pract Cardiovasc Med"},{"key":"2024103012313231500_jphp13000-cit-0015","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1124\/jpet.111.190132","article-title":"Fumarates promote cytoprotection of central nervous system cells against oxidative stress via the nuclear factor (erythroid-derived 2)-like 2 pathway","volume":"341","author":"Scannevin","year":"2012","journal-title":"J Pharmacol Exp Ther"},{"key":"2024103012313231500_jphp13000-cit-0016","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1586\/14737175.2015.1025755","article-title":"Dimethyl fumarate in relapsing\u2013remitting multiple sclerosis: rationale, mechanisms of action, pharmacokinetics, efficacy and safety","volume":"15","author":"Dubey","year":"2015","journal-title":"Expert Rev Neurother"},{"key":"2024103012313231500_jphp13000-cit-0017","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.ejphar.2008.02.038","article-title":"Dimethyl fumarate, a small molecule drug for psoriasis, inhibits nuclear factor-\u03baB and reduces myocardial infarct size in rats","volume":"586","author":"Meili-Butz","year":"2008","journal-title":"Eur J Pharmacol"},{"key":"2024103012313231500_jphp13000-cit-0018","doi-asserted-by":"crossref","first-page":"31159","DOI":"10.1038\/srep31159","article-title":"Dimethyl fumarate blocks pro-inflammatory cytokine production via inhibition of TLR induced M1 and K63 ubiquitin chain formation","volume":"6","author":"McGuire","year":"2016","journal-title":"Sci Rep"},{"key":"2024103012313231500_jphp13000-cit-0019","first-page":"3217","article-title":"Simvastatin prevents isoproterenol-induced cardiac hypertrophy through modulation of the JAK\/STAT pathway","volume":"9","author":"Al-Rasheed","year":"2015","journal-title":"Drug Des Devel Ther"},{"key":"2024103012313231500_jphp13000-cit-0020","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1097\/TP.0000000000000647","article-title":"Treatment with dimethyl fumarate attenuates calcineurin inhibitor-induced nephrotoxicity","volume":"99","author":"Takasu","year":"2015","journal-title":"Transplantation"},{"key":"2024103012313231500_jphp13000-cit-0021","first-page":"1291","article-title":"Measuring blood pressure in mice using volume pressure recording, a tail-cuff method","volume":"27","author":"Daugherty","year":"2009","journal-title":"J Vis Exp"},{"key":"2024103012313231500_jphp13000-cit-0022","doi-asserted-by":"crossref","first-page":"868753","DOI":"10.1155\/2014\/868753","article-title":"Rapamycin attenuated cardiac hypertrophy induced by isoproterenol and maintained energy homeostasis via inhibiting NF-\u03baB activation","volume":"2014","author":"Chen","year":"2014","journal-title":"Mediators Inflamm"},{"key":"2024103012313231500_jphp13000-cit-0023","doi-asserted-by":"crossref","first-page":"H211","DOI":"10.1152\/ajpheart.00581.2007","article-title":"Effects of isoproterenol treatment for 7 days on inflammatory mediators in the rat aorta","volume":"295","author":"Davel","year":"2008","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2024103012313231500_jphp13000-cit-0024","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1111\/j.1742-7843.2008.00261.x","article-title":"L-arginine inhibits isoproterenol-induced cardiac hypertrophy through nitric oxide and polyamine pathways","volume":"103","author":"Lin","year":"2008","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"2024103012313231500_jphp13000-cit-0025","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1097\/FJC.0000000000000410","article-title":"Inhibition of TNF-\u03b1-mediated NF-\u03baB activation by Ginsenoside Rg1 contributes the attenuation of cardiac hypertrophy induced by abdominal aorta coarctation","volume":"68","author":"Tang","year":"2016","journal-title":"J Cardiovasc Pharmacol"},{"key":"2024103012313231500_jphp13000-cit-0026","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1002\/tox.22267","article-title":"Toll-like receptor 4 ablation rescues against paraquat-triggered myocardial dysfunction: role of ER stress and apoptosis","volume":"32","author":"Lei","year":"2017","journal-title":"Environ Toxicol"},{"key":"2024103012313231500_jphp13000-cit-0027","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1146\/annurev.physiol.65.092101.142243","article-title":"Cardiac hypertrophy: the good, the bad, and the ugly","volume":"65","author":"Frey","year":"2003","journal-title":"Annu Rev Physiol"},{"key":"2024103012313231500_jphp13000-cit-0028","doi-asserted-by":"crossref","first-page":"6341","DOI":"10.1093\/emboj\/19.23.6341","article-title":"The MEK1-ERK1\/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice","volume":"19","author":"Bueno","year":"2000","journal-title":"EMBO J"},{"key":"2024103012313231500_jphp13000-cit-0029","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/S1053-2498(00)00083-8","article-title":"Prognostic value of serum cytokines in patients with congestive heart failure","volume":"19","author":"Or\u00fas","year":"2000","journal-title":"J Heart Lung Transplant"},{"key":"2024103012313231500_jphp13000-cit-0030","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1161\/01.CIR.99.4.546","article-title":"Cardiac myocytes produce interleukin-6 in culture and in viable border zone of reperfused infarctions","volume":"99","author":"Gwechenberger","year":"1999","journal-title":"Circulation"},{"key":"2024103012313231500_jphp13000-cit-0031","doi-asserted-by":"crossref","first-page":"32124","DOI":"10.1074\/jbc.M203298200","article-title":"The phosphatidylinositol 3-kinase-Akt pathway limits lipopolysaccharide activation of signaling pathways and expression of inflammatory mediators in human monocytic cells","volume":"277","author":"Guha","year":"2002","journal-title":"J Biol Chem"},{"key":"2024103012313231500_jphp13000-cit-0032","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/S1471-4906(03)00139-X","article-title":"PI3K and negative regulation of TLR signaling","volume":"24","author":"Fukao","year":"2003","journal-title":"Trends Immunol"}],"container-title":["Journal of Pharmacy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjphp.13000","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/70\/11\/1521\/60223729\/jphp13000.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/70\/11\/1521\/60223729\/jphp13000.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T13:41:08Z","timestamp":1730295668000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpp\/article\/70\/11\/1521\/6121745"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,1]]},"references-count":32,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2018,11,1]]},"published-print":{"date-parts":[[2018,11,1]]}},"URL":"https:\/\/doi.org\/10.1111\/jphp.13000","relation":{},"ISSN":["0022-3573","2042-7158"],"issn-type":[{"value":"0022-3573","type":"print"},{"value":"2042-7158","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2018,11]]},"published":{"date-parts":[[2018,11,1]]}}}