2. Academic Validation
  3. Vitamin B12 alleviates myocardial ischemia/reperfusion injury via the SIRT3/AMPK signaling pathway

Vitamin B12 alleviates myocardial ischemia/reperfusion injury via the SIRT3/AMPK signaling pathway

  • Biomed Pharmacother. 2023 Apr 29;163:114761. doi: 10.1016/j.biopha.2023.114761.
Yuhong Qin 1,  Yani Shi 2,  Qi Yu 3,  Shenglan Yang 3,  Ying Wang 3,  Xiaojia Dai 4,  Guoxing Li 5,  Zhe Cheng 6
Affiliations

Affiliations

  • 1 Department of Hepatology and Translational Medicine, Chongqing University Fuling Hospital, Chongqing 400016, China.
  • 2 Department of General medicine, Chongqing University Fuling Hospital, Chongqing 400016, China.
  • 3 Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
  • 4 Clinic Medical College, Southwest Medical University, Sichuan 646099, China.
  • 5 Institute of Life Sciences, Chongqing Medical University, 400016, China. Electronic address: [email protected].
  • 6 Institute of Life Sciences, Chongqing Medical University, 400016, China; Department of Cardiology, Chongqing University Three Gorges Hospital & Chongqing Three Gorges Central Hospital, 404000, China. Electronic address: [email protected].
PMID: 37126929 DOI: 10.1016/j.biopha.2023.114761
Abstract

Aim: To examine the protective effect of vitamin B12 against myocardial ischemia/reperfusion (I/R) injury and elucidate its underlying mechanism of action.

Methods: Mice were subjected to myocardial I/R injury by left anterior descending coronary artery (LAD) occlusion followed by 24 h reperfusion. Cardiac function and injury were evaluated by echocardiography, triphenyl tetrazolium chloride (TTC) and cardiac troponin T (cTnT) staining, and measuring Lactate Dehydrogenase (LDH) levels. In addition, various molecular and biochemical methods, as well as RNA sequencing were used to determine the effects and mechanism of action of vitamin B12 on I/R injury.

Results: We found that high doses of vitamin B12 inhibited myocardial I/R injury. Furthermore, our data indicated that vitamin B12 supplementation alleviated cardiac dysfunction and injury by mitigating oxidative stress and Apoptosis through downregulation of Nox2, the Ac-SOD2/SOD2 and Bax/Bcl-2 ratios and cleaved Caspase-3 expression, and upregulation of SIRT3 expression and AMPK activity. However, these effects were largely reversed following treatment with the SIRT3 Inhibitor, 3-TYP. Our RNA-sequencing data further demonstrated that vitamin B12 supplementation reduced inflammation during I/R injury.

Conclusion: High doses of vitamin B12 supplements improved myocardial I/R injury by suppressing the accumulation of Reactive Oxygen Species and Apoptosis of myocardial tissue through modulation of the SIRT3/AMPK signaling pathway, while reducing inflammation. Our findings suggested that vitamin B12 administered at high doses could be a potential therapy for myocardial I/R damage.

Keywords

AMPK; Myocardial ischemia/reperfusion injury; SIRT3; Vitamin B12.

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