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Current evidence suggests that aging and age\u2010releated comorbidities impair the cardioprotective effects of conditionings. In conjuction with aging, decrease in melatonin synthesis from pineal gland can have role in the pathogenesis of aging and age\u2010related cardiovascular diseases. In this study, we investigated the effects of remote ischemic perconditioning (RIPerC) and physiological and pharmacological concentrations of melatonin on the infarct size, Fas gene, cytochrome b\u2010245 beta chain (Cybb) gene, nuclear factor\u2010kappa B (Nf\u03baB), and irisin using an in vivo model of myocardial ischemia\/reperfusion (I\/R) injury. Sprague\u2010Dawley rats that were divided into two groups first as non\u2010pinealectomized (Non\u2010Px) and pinealectomized (Px), and then (a) Control; (b) I\/R (30\u2010minute ischemia, 120\u2010minute reperfusion caused by left coronary artery ligation); (c) I\/R\u00a0+\u00a0RIPerC (when myocardial ischemia initiated, three cycles of 5\u2010minute occlusion followed by 5\u2010minute reperfusion); (d) I\/R\u00a0+\u00a0Mel; (e) Px; (f) Px\u00a0+\u00a0I\/R; (g) Px\u00a0+\u00a0I\/R\u00a0+\u00a0RIPerC; (h) Px\u00a0+\u00a0I\/R\u00a0+\u00a0RIPerC\u00a0+\u00a0Mel groups. The infarct size was determined by TTC staining and analyzed by the ImageJ program. Molecular parameters were evaluated by qRT\u2010PCR and Western blot. Results showed that increased infarct size in Non\u2010Px groups decreased with RIPerC and melatonin. However, increased infarct size in Px groups was decreased minimally with RIPerC and significantly decreased with RIPerC\u00a0+\u00a0Melatonin. Fold change in Fas gene was associated with the infarct size. RIPerC and melatonin reduced expressions of Cybb, Nf\u03baB, and irisin genes. The physiological release and pharmacological concentration of melatonin may improve protective effect of RIPerC against I\/R\u2010induced infarct size by modulating Cybb, Fas, Nf\u03baB, Irisin signaling pathways.<\/jats:p>","DOI":"10.1111\/jpi.12589","type":"journal-article","created":{"date-parts":[[2019,6,3]],"date-time":"2019-06-03T06:53:02Z","timestamp":1559544782000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Physiological and pharmacological effects of melatonin on remote ischemic perconditioning after myocardial ischemia\u2010reperfusion injury in rats: Role of Cybb, Fas, Nf\u03baB, Irisin signaling pathway"],"prefix":"10.1111","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2899-3502","authenticated-orcid":false,"given":"Kubra","family":"Gul\u2010Kahraman","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine Firat University Elazig Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6058-4579","authenticated-orcid":false,"given":"Merve","family":"Yilmaz\u2010Bozoglan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine Firat University Elazig Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8311-9055","authenticated-orcid":false,"given":"Engin","family":"Sahna","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine Firat University Elazig 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