Evidence map›Paper›PMID 33866495›Full record

ArticleMolecular biology reports2021

Nicotinamide mononucleotide and melatonin counteract myocardial ischemia-reperfusion injury by activating SIRT3/FOXO1 and reducing apoptosis in aged male rats.

Aida Jafari-Azad, Leila Hosseini, Mojgan Rajabi, Poul Flemming Høilund-Carlsen, Manouchehr Seyedi Vafaee, Saeid Feyzizadeh, Reza Badalzadeh

Abstract read
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In one paragraph

Article in Molecular biology reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
2.2field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.

  1. Pooled it
  2. Cellular and molecular mechanisms underlying cardiovascular aging.Cellular & molecular biology letters · 2025
    Review
  3. Review
  4. The Role of NADAmerican journal of cardiovascular drugs : drugs, devices, and other interventions · 2025
    Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Nicotinamide Mononucleotide: Research Process in Cardiovascular Diseases.International journal of molecular sciences · 2024
    Review
  10. NAD in pathological cardiac remodeling: Metabolic regulation and beyond.Biochimica et biophysica acta. Molecular basis of disease · 2024
    Review
  11. Article
  12. Review
  13. Article
  14. Sevoflurane preconditioning alleviates myocardial ischemia reperfusion injury through mitochondrial NADZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2022
    Article
  15. Article
  16. Article
  17. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Aida Jafari-AzadDrug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Leila HosseiniDrug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Mojgan RajabiDrug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Poul Flemming Høilund-CarlsenDepartment of Nuclear Medicine, Odense University Hospital, Odense, Denmark.
Manouchehr Seyedi VafaeeDepartment of Nuclear Medicine, Odense University Hospital, Odense, Denmark.
Saeid FeyzizadehDrug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Reza BadalzadehMolecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. badalzadehr@tbzmed.ac.ir.
Tabriz University of Medical Sciences · IROdense University Hospital · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

It has been documented that aging increases the risk of cardiovascular disease including myocardial ischemia/reperfusion (IR) injury and acute myocardial infarction. In this study, we aimed to investigate the individual or combined effects of nicotinamide mononucleotide (NMN) and melatonin (Mel) treatment on apoptotic markers, expression of SIRT3, and FOXO1, and infarct size of the aged myocardium subjected to IR injury. Sixty aged Wistar rats (22-24 months) were assigned to five groups including sham, IR, NMN+IR, Mel+IR, and NMN+Mel+IR (combination therapy). Isolated hearts were exposed to 30-min regional ischemia followed by 60-min reperfusion. NMN (100 mg/kg/day/i.p.) was injected every second day starting on day 28 before IR injury. Melatonin was added to the perfusion solution five minutes prior to and until 15 min after the start of reperfusion. The infarct size was assessed by computerized planimetry. The mRNA levels of SIRT3, FOXO1, and apoptotic genes Bax, Bcl-2, and Caspase-3 were estimated by real-time PCR. All treatments reduced infarct size as compared with the IR group. Melatonin and NMN upregulated the gene expression of Bcl-2, SIRT3, and FOXO1 and downregulated the gene expression of Bax, and Caspase-3, in comparison to the IR group. Also, the protein levels of SIRT3, quantified by Western blotting, were upregulated by the interventions. The effects of combination therapy were significantly greater than those of melatonin or NMN alone. These findings indicate that the combined administration of NMN and melatonin can protect the aged heart against IR injury by decreasing apoptosis and activating the SIRT3/FOXO1 pathway.

Indexed as

Myocardial Reperfusion InjuryAgingAnimalsApoptosisDrug CombinationsForkhead Box Protein O1HeartMaleMelatoninNerve Tissue ProteinsNicotinamide MononucleotideRatsRats, WistarSignal TransductionSirtuin 3Drug CombinationsForkhead Box Protein O1MelatoninNerve Tissue ProteinsNicotinamide MononucleotideSirtuin 3AgingCell deathIschemia-reperfusion injuryMelatoninNMN

Identifiers

PMID33866495
OpenAlexW3155533503

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.