{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T22:51:07Z","timestamp":1790549467938,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,9,26]],"date-time":"2016-09-26T00:00:00Z","timestamp":1474848000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002836","name":"Chang Gung University","doi-asserted-by":"publisher","award":["CMRPG8D0611"],"award-info":[{"award-number":["CMRPG8D0611"]}],"id":[{"id":"10.13039\/501100002836","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2016,11]]},"abstract":"Abstract<\/jats:title>We investigated the cardioprotective effect of melatonin (Mel) and exendin\u20104 (Ex4) treatment in a rat model of cardiorenal syndrome (CRS<\/jats:styled-content>). Adult maleSD<\/jats:styled-content>rats (n=48) were randomly and equally divided into sham control (SC<\/jats:styled-content>), dilated cardiomyopathy (DCM<\/jats:styled-content>) (doxorubicin 7\u00a0mg\/kg i.p. every five days\/4 doses),CRS<\/jats:styled-content>(defined asDCM<\/jats:styled-content>+CKD<\/jats:styled-content>) only,CRS<\/jats:styled-content>\u2010Mel (20\u00a0mg\/kg\/d),CRS<\/jats:styled-content>\u2010Ex4 (10\u00a0\u03bcg\/kg\/d), andCRS<\/jats:styled-content>\u2010Mel\u2010Ex4 groups. In vitro results showed protein expressions of oxidative stress (NOX<\/jats:styled-content>\u20101\/NOX<\/jats:styled-content>\u20102\/oxidized protein),DNA<\/jats:styled-content>\/mitochondrial damage (\u03b3\u2010H2AX<\/jats:styled-content>\/cytosolic cytochrome c), apoptosis (cleaved caspase\u20103\/PARP<\/jats:styled-content>), and senescence (\u03b2\u2010galactosidase cells) biomarkers were upregulated, whereas mitochondrialATP<\/jats:styled-content>level was decreased in doxorubicin\/p\u2010cresol\u2010treated H9c2 cells that were revised by Mel and Ex4 treatments (allP<\/jats:italic><.001). By day 60,LVEF<\/jats:styled-content>was highest in theSC<\/jats:styled-content>and lowest in theCRS<\/jats:styled-content>, significantly lower in theDCM<\/jats:styled-content>than in other treatment groups, lower in theCRS<\/jats:styled-content>\u2010Mel andCRS<\/jats:styled-content>\u2010Ex4 than in theCRS<\/jats:styled-content>\u2010Mel\u2010Ex4, and lower in theCRS<\/jats:styled-content>\u2010Mel than in theCRS<\/jats:styled-content>\u2010Ex4, whereasLV<\/jats:styled-content>chamber size and histopathology score showed a pattern opposite to that ofLVEF<\/jats:styled-content>among all groups (allP<\/jats:italic><.001). Plasma creatinine level was highest in theCRS<\/jats:styled-content>and lowest in theSC<\/jats:styled-content>and progressively decreased from theCRS<\/jats:styled-content>\u2010Mel,CRS<\/jats:styled-content>\u2010Ex4,CRS<\/jats:styled-content>\u2010Mel\u2010Ex4 toDCM<\/jats:styled-content>(P<\/jats:italic><.0001). Protein expressions of inflammation (TNF<\/jats:styled-content>\u2010\u03b1\/NF<\/jats:styled-content>\u2010\u03baB\/MMP<\/jats:styled-content>\u20102\/MMP<\/jats:styled-content>\u20109\/IL<\/jats:styled-content>\u20101\u03b2), apoptosis\/DNA<\/jats:styled-content>damage (Bax\/c\u2010caspase\u20103\/c\u2010PARP<\/jats:styled-content>\/\u03b3\u2010H2AX<\/jats:styled-content>), fibrosis (Smad3\/TGF<\/jats:styled-content>\u2010\u03b2), oxidative stress (NOX<\/jats:styled-content>\u20101\/NOX<\/jats:styled-content>\u20102\/NOX<\/jats:styled-content>\u20104\/oxidized protein), cardiac hypertrophy\/pressure overload (BNP<\/jats:styled-content>\/\u03b2\u2010MHC<\/jats:styled-content>), and cardiac integrity (Cx43\/\u03b1\u2010MHC<\/jats:styled-content>) biomarkers inLV<\/jats:styled-content>myocardium showed an opposite pattern compared to that ofLVEF<\/jats:styled-content>among all groups (allP<\/jats:italic><.001). Fibrotic area,DNA<\/jats:styled-content>damage (\u03b3\u2010H2AX<\/jats:styled-content>+<\/jats:sup>\/53BP<\/jats:styled-content>1+<\/jats:sup>CD<\/jats:styled-content>90+<\/jats:sup>\/XRCC<\/jats:styled-content>1+<\/jats:sup>CD<\/jats:styled-content>90+<\/jats:sup>), and inflammation (CD<\/jats:styled-content>14+<\/jats:sup>\/CD<\/jats:styled-content>68+<\/jats:sup>) biomarkers inLV<\/jats:styled-content>myocardium displayed a pattern opposite to that ofLVEF<\/jats:styled-content>among all groups (allP<\/jats:italic><.001). Combined melatonin and exendin\u20104 treatment suppressedCRS<\/jats:styled-content>\u2010induced deterioration ofLVEF<\/jats:styled-content>andLV<\/jats:styled-content>remodeling.<\/jats:p>","DOI":"10.1111\/jpi.12357","type":"journal-article","created":{"date-parts":[[2016,7,28]],"date-time":"2016-07-28T11:17:24Z","timestamp":1469704644000},"page":"438-456","source":"Crossref","is-referenced-by-count":72,"title":["The cardioprotective effect of melatonin and exendin\u20104 treatment in a rat model of cardiorenal syndrome"],"prefix":"10.1111","volume":"61","author":[{"given":"Sarah","family":"Chua","sequence":"first","affiliation":[{"name":"Division of Cardiology Department of Internal Medicine Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan\u2010Yen","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of thoracic and Cardiovascular Surgery Department of Surgery Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin\u2010Ju","family":"Chiang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan\u2010Hung","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences National Sun Yat\u2010Sen University Kaohsiung Taiwan"},{"name":"Department of Anesthesiology Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung\u2010I","family":"Lu","sequence":"additional","affiliation":[{"name":"Division of thoracic and Cardiovascular Surgery Department of Surgery 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