Nicotinamide riboside attenuates myocardial ischemia-reperfusion injury via regulating SIRT3/SOD2 signaling pathway

 Hopefully your competent? doctor is fully aware of what this can do.

• Nicotinamide riboside (2 posts to April 2016)

Nicotinamide riboside attenuates myocardial ischemia-reperfusion injury via regulating SIRT3/SOD2 signaling pathway

Author links open overlay panel

, , , , , , , ,

https://doi.org/10.1016/j.biopha.2024.116689Get rights and content

Under a Creative Commons license

open access

Highlights

• •

  Exploring of the most effective dose regimen for NR in rats and H9c2 cells.

• •

  Mitochondrial oxidative stress is the main cause of myocardial I/R injury.

• •

  Regulation of SIRT3/SOD2/mtROS pathway can alleviate myocardial I/R injury.

• •

  NR attenuates myocardial I/R injury through SIRT3/SOD2/mtROS pathway.

Abstract

Ischemic heart disease invariably leads to devastating damage to human health. Nicotinamide ribose (NR), as one of the precursors of NAD⁺ synthesis, has been discovered to exert a protective role in various neurological and cardiovascular disorders. Our findings demonstrated that pretreatment with 200 mg/kg NR for 3 h significantly reduced myocardial infarct area, decreased levels of CK-MB and LDH in serum, and improved cardiac function in the rats during myocardial ischemia-reperfusion (I/R) injury. Meanwhile, 0.5 mM NR also effectively increased the viability and decreased the LDH release of H9c2 cells during OGD/R. We had provided evidence that NR pretreatment could decrease mitochondrial reactive oxygen species (mtROS) production and MDA content, and enhance SOD activity, thereby mitigating mitochondrial damage and inhibiting apoptosis during myocardial I/R injury. Further investigations revealed that NR increased NAD⁺ content and upregulated SIRT3 protein expression in myocardium. Through using of SIRT3 small interfering RNA and the SIRT3 deacetylase activity inhibitor 3-TYP, we had confirmed that the cardioprotective effect of NR on cardiomyocytes was largely dependent on the inhibition of mitochondrial oxidative stress via SIRT3-SOD2 axis. Overall, our study suggested that exogenous supplementation with NR mitigated mitochondrial damage and inhibited apoptosis during myocardial I/R injury by reducing mitochondrial oxidative stress via SIRT3-SOD2-mtROS pathway.

Graphical Abstract

1. Download : Download high-res image (203KB)
2. Download : Download full-size image

Our findings demonstrate that pretreatment with NR significantly reduces myocardial infarct area, decreases levels of CK-MB and LDH in serum, and improves cardiac function in the rats during myocardial ischemia-reperfusion (I/R) injury. Meanwhile, NR also effectively increases the viability and decreases the LDH release of H9c2 cells during OGD/R. Mechanically, we have provided evidence that NR pretreatment could decrease mitochondrial reactive oxygen species (mtROS) production and MDA content, and enhance SOD activity, thereby mitigating mitochondrial damage and inhibiting apoptosis during myocardial I/R injury. Further investigations revealed that NR increased NAD⁺ content and upregulated SIRT3 protein expression in myocardium. Through using of SIRT3 small interfering RNA and the SIRT3 deacetylase activity inhibitor 3-TYP, we have confirmed that the cardioprotective effect of NR on cardiomyocytes was largely dependent on the inhibition of mitochondrial oxidative stress via SIRT3-SOD2 axis. Overall, our comprehensive exploration into the mechanisms underlying NR-mediated myocardial protection will provide a theoretical foundation for prevention and therapy on myocardial I/R injury.

More at link.