Veterinary Research Forum

A combination of melatonin and nicotinamide mononucleotide alleviates inflammation and enhances isolated heart function in aged rats following ischemia-reperfusion injury

Document Type : Original Article

Authors

Paria Amanzadeh 1
Bagher Pourheydar 2
Naeimeh Akbari-Gharalari 3
Leila Chodari 1, 3
Reza Badalzadeh 4, 5

1 Department of Physiology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran

2 Department of Anatomical Sciences, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran

3 Neurophysiology Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran

4 Department of Physiology, Faculty of medicine, Tabriz University of Medical Sciences, Tabriz, Iran

5 Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

https://doi.org/10.30466/vrf.2026.2065344.4826
Abstract
Aging markedly increases vulnerability to cardiovascular disorders, including acute coronary syndrome and coronary artery disease. Although melatonin (M) and nicotinamide mono-nucleotide (N) have each shown cardioprotective properties, their combined effects on ischemia-reperfusion (IR) injury in the aged heart remain unclear. This study investigated co-administration of M and N enhances cardiac functional recovery and reduces inflammatory responses following myocardial IR injury in aged rats. Forty adult male Wistar rats (n = 8/group) were randomly assigned to five groups: Sham, IR, M (IR + M), N (IR + N), and N + M (IR + N + M). Cardiac function was evaluated after IR by measuring coronary flow, heart rate, left ventricular end-diastolic pressure, and left ventricular developed pressure. Melatonin was administered at 50.00 µM in the reperfusion solution for 15 min after 30 min of ischemia, N was administered intraperitoneally at 100 mg kg-1 every other day for 28 days. Creatine kinase and inflammatory markers, including interleukin IL-1β, IL-6, tumor necrosis factor-alpha, and nuclear factor kappa B, were also assessed. IR significantly impaired coronary flow and heart rate, both of which were improved by M and N treatment. These agents also reduced left ventricular end-diastolic pressure and improved left ventricular developed pressure recovery, with the combined therapy producing the greatest effect. Likewise, creatine kinase and inflammatory marker levels were significantly elevated in the IR group but markedly reduced by treatment, especially by combined administration. These findings suggest that M and N exert additive cardioprotective effects against IR injury in aged rats.

Keywords

Hemodynamic parameters
Inflammation
Melatonin
Nicotinamide mononucleotide
Subjects
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Veterinary Research Forum
Volume 17, Issue 9
September 2026
Pages 653-662

  • Receive Date 21 July 2025
  • Revise Date 08 October 2025
  • Accept Date 07 January 2026

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