Article, 2023

Melatonin/nicotinamide mononucleotide/ubiquinol: a cocktail providing superior cardioprotection against ischemia/reperfusion injury in a common co-morbidities modelled rat

In: Molecular Biology Reports, ISSN 1573-4978, 0301-4851, Volume 50, 4, Pages 3525-3537, 10.1007/s11033-022-08189-0

Contributors (6)

Mokhtari, Behnaz (0000-0002-3355-9869) [1] Høilund-Carlsen, Poul Flemming Høilund (0000-0001-7420-2367) [2] [3] Chodari, Leila (0000-0002-9263-8583) [4] Yasami, Masoud [1] Badalzadeh, Reza (0000-0002-8092-7820) (Corresponding author) [1] Ghaffari, Samad (0000-0001-6806-9387) (Corresponding author) [1]


  1. [1] Tabriz University of Medical Sciences
  2. [NORA names: Iran; Asia, Middle East]
  3. [2] Odense University Hospital
  4. [NORA names: Region of Southern Denmark; Hospital; Denmark; Europe, EU; Nordic; OECD]
  5. [3] University of Southern Denmark
  6. [NORA names: SDU University of Southern Denmark; University; Denmark; Europe, EU; Nordic; OECD]
  7. [4] Urmia University of Medical Sciences


BackgroundThe metabolic and intracellular abnormalities in aging and diabetes cause loss of cardioprotection by routine interventions against myocardial ischemia/reperfusion (I/R) injury. We aimed to evaluate the possible interaction of aging and type-2 diabetes mellitus with cardioprotection and the potential protective effect of a mitochondrial cocktail (melatonin/nicotinamide mononucleotide (NMN)/ubiquinol) on myocardial I/R injury in aged diabetic rats.MethodsMale Wistar rats (n = 108, 22–24 months old, 400–450 g) received high-fat diet/low dose of streptozotocin to induce type-2 diabetes, then were randomized into 9 groups of 12 rats each with/without I/R and/or melatonin, NMN, and ubiquinol, alone or in dual or triple combinations. Myocardial I/R was induced by LAD occlusion for 30 min followed by 24 h reperfusion. NMN (100 mg/kg/48 h, intraperitoneally) was administered for 28 days before I/R operation. Melatonin (10 mg/kg, intraperitoneally) and/or ubiquinol (30 mg/kg, intravenously) were administered at early reperfusion. Finally, hemodynamic index changes, infarct size, CK-MB levels, mitochondrial functional endpoints, and expression of mitochondrial biogenesis genes (SIRT-1/PGC-1α/NRF-2/TFAM) were assessed.ResultsThe solo and dual applications of melatonin, NMN, and ubiquinol did not exert remarkable cardioprotective impacts. However, the triple combination improved myocardial function and decreased infarct size and CK-MB levels following myocardial I/R (P < .05 to P < .01). It also improved mitochondrial function and restored mitochondrial biogenesis genes (P < .01).ConclusionsCombination therapy with melatonin, NMN, and ubiquinol exerted significant cardioprotection and improved mitochondrial function and biogenesis via upregulation of SIRT-1/PGC-1α/NRF-2/TFAM profiles in aged diabetic rats and, thus, offers a promising strategy for providing noticeable cardioprotection against I/R injury also in aged diabetic patients.


BackgroundThe, CK-MB levels, ConclusionsCombination therapy, LAD occlusion, MethodsMale Wistar, Myocardial I/R, NMN, NRF, PGC-1α/NRF, R injury, R operation, Wistar, abnormalities, aged diabetic rats, aging, applications, biogenesis, biogenesis genes, cardioprotection, cardioprotective impact, changes, cocktail, combination, days, diabetes, diabetes mellitus, diabetic patients, diabetic rats, dose, dual application, early reperfusion, effect, endpoint, expression, function, functional endpoints, genes, group, h reperfusion, impact, index change, infarct size, injury, interaction, intervention, intracellular abnormalities, ischemia/reperfusion injury, levels, loss, loss of cardioprotection, low dose, melatonin, mellitus, min, mitochondrial biogenesis genes, mitochondrial cocktail, mitochondrial function, myocardial function, myocardial ischemia/reperfusion injury, occlusion, operation, patients, possible interactions, potential protective effect, profile, promising strategy, protective effect, rats, reperfusion, reperfusion injury, routine intervention, significant cardioprotection, size, solo, strategies, streptozotocin, superior cardioprotection, therapy, triple combination, type 2 diabetes, type 2 diabetes mellitus, ubiquinol, upregulation


  • Tabriz University of Medical Sciences