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Ischemic postconditioning reduced myocardial ischemia-reperfusion injury: The roles of melatonin and uncoupling protein 3 [Anatol J Cardiol]
Anatol J Cardiol. 2020; 23(1): 19-27 | DOI: 10.14744/AnatolJCardiol.2019.72609  

Ischemic postconditioning reduced myocardial ischemia-reperfusion injury: The roles of melatonin and uncoupling protein 3

Gülnur Aslan1, Hüseyin Fatih Gül2, Ahmet Tektemur3, Engin Sahna1
1Department of Pharmacology, Faculty of Medicine, Firat University, Elazig, TURKEY
2Department of Biochemistry, Faculty of Medicine, Firat University, Elazig, TURKEY
3Department of Medical Biology, Faculty of Medicine, Firat University, Elazig, TURKEY

Objective: Protective effects of ischemic postconditioning (PostC) decrease/disappear with age and chronic heart diseases. Similarly, low serum melatonin levels have been reported in the same risk groups. The aims of this study were to investigate the effects of melatonin on the protection of PostC in ischemia–reperfusion (I/R)-induced infarct size and roles of uncoupling protein (UCP) 3, irisin, and nuclear factor kappa B (NFkB) levels.
Methods: Rats were pinealectomized (Px) or sham operated (non-Px) 2 months before the I/R studies. The left main coronary artery was occluded for 30 min followed by 120 min reperfusion. PostC was induced with three cycles of R/I (10 s each) after ischemia.
Results: The infarct size was found to be significantly higher in Px rats (54.68±1.5%) than in the control group (35.1±2.5%). PostC and melatonin administrations to non-Px rats significantly reduced the infarct size. On the other hand, PostC did not create a significant effect in Px rats, but protection was provided when PostC was co-administrated with melatonin. While significant decreases were detected in the UCP3 levels, irisin and NFkB levels increased with I/R and Px. Treatment with PostC and melatonin in non-Px groups and their co-administration in Px groups were found to return all the genes close to normal levels.
Conclusion: The physiological and pharmacological concentrations of melatonin may play a role in the protection of PostC. In cases when physiological melatonin is reduced, such as aging and heart diseases, this protection may decrease, and this effect may be restored by melatonin replacement. PostC and melatonin may regulate energy metabolism and inflammatory mediators and protect mitochondria by affecting the UCP3, irisin, and NFkB levels.

Keywords: Reperfusion injury, postconditioning, melatonin, uncoupling protein 3, irisin, nuclear factor kappa B


İskemik ardkoşullanma, miyokardiyal iskemi-reperfüzyon hasarını azalttı: Melatonin ve uncoupling protein 3'ün rolleri

Gülnur Aslan1, Hüseyin Fatih Gül2, Ahmet Tektemur3, Engin Sahna1
1Fırat Üniversitesi Tıp Fakültesi, Farmakoloji Anabilim Dalı, Elazığ, TÜRKİYE
2Fırat Üniversitesi Tıp Fakültesi, Biyokimya Anabilim Dalı, Elazığ, TÜRKİYE
3Fırat Üniversitesi Tıp Fakültesi, Tıbbi Biyoloji Anabilim Dalı, Elazığ, TÜRKİYE

Amaç: İskemik ardkoşullanma (PostC)’nın koruyucu etkileri yaş ve kronik kalp hastalıklarıyla ile birlikte azalır/ortadan kalkar. Benzer şekilde, aynı risk gruplarında düşük serum melatonin düzeyleri de bildirilmiştir. Bu çalışmanın amacı, iskemi-reperfüzyon (I/R) hasarında PostC'nin koruyuculuğunda melatoninin etkilerini araştırmaktır.
Metod: Sıçanlar, I/R çalışmalarından 2 ay önce pinealektomize (Px) veya sham (non-Px) ikiye ayrıldı. Sol ana koroner artere 30 dakika iskemi ve 120 dakika reperfüzyon uygulandı. PostC, iskemiden sonra 3 siklus R/I (her biri 10 s) ile indüklendi.
Bulgular: İnfarkt alanı Px sıçanlarda (54,68 ± 1,5%) kontrol grubundan (35,1 ± 2,5%) anlamlı olarak yüksek bulundu. Non-Px sıçanlarda PostC ve melatonin uygulamaları infarkt alanını anlamlı azalttı. Öte yandan, Px sıçanlarda PostC anlamlı bir etki oluşturmazken, melatonin ile birlikte uygulandığında koruma görüldü. UCP3 seviyeleri I/R ve Px ile azaldı, PostC ve melatonin ile arttı.
Sonuç: Melatoninin fizyolojik ve farmakolojik konsantrasyonlarının PostC’nin koruyuculuğunda rolü olabilir. Yaşlanma ve kalp hastalıkları gibi fizyolojik melatoninin azaldığı durumlarda koruyuculuk azalabilir ve melatonin replasmanı bu etkiyi geri getirebilir. PostC ve melatonin; UCP3, irisin ve NFkB seviyelerini etkileyerek enerji metabolizmasını ve enflamatuar mediatörleri düzenleyebilir ve mitokondriyi koruyabilir.

Anahtar Kelimeler: Reperfüzyon hasarı, Ardkoşullanma, Melatonin, UCP3, irisin, NFkB


Gülnur Aslan, Hüseyin Fatih Gül, Ahmet Tektemur, Engin Sahna. Ischemic postconditioning reduced myocardial ischemia-reperfusion injury: The roles of melatonin and uncoupling protein 3. Anatol J Cardiol. 2020; 23(1): 19-27

Corresponding Author: Gülnur Aslan, Türkiye


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