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Preclinical mechanistic study

Nicotinamide mononucleotide as a therapeutic agent to alleviate multi-organ failure in sepsis

Ting Cao, Rui Ni, Weimin Ding, Xiaoyun Ji, Guo-Chang Fan, Zhuxu Zhang, Tianqing Peng

Journal of Translational Medicine · 2023 · 21(1):883

Original publication PubMed Full text on PMC

Study at a glance

Design
Preclinical sepsis intervention study using feces-injection-in-peritoneum mouse models plus macrophage, neutrophil, and endothelial-cell experiments.
Population or model
Male C57BL/6 mice and cultured immune/endothelial cells; no human participants.
Sample size
Initial four-group experiment used 15 mice per group; organ analyses commonly used n=8 per group; 24-hour survival used 25 septic mice per arm, and 30-day survival used 22 per arm.
Intervention
NMN given intraperitoneally one hour after sepsis induction. Acute experiments used 500 mg/kg; a lower-severity 30-day survival model used 100 mg/kg every other day after the initial post-sepsis dose.
Publication type
Preclinical mechanistic study
Evidence class
preclinical-mechanistic
Research area
Sepsis and multi-organ injury
Trial registration
Not applicable (animal and cellular study)

Study endpoints

  • Tissue NAD+ and serum lactate
  • Cardiac function and pulmonary microvascular permeability
  • Liver and kidney injury/dysfunction
  • Oxidative stress, inflammation, and apoptosis
  • Blood bacterial burden and innate immune bactericidal activity
  • Short- and long-term survival
  • SIRT3-dependent endothelial mitochondrial and barrier function

Plain-language summary

This preclinical study tested NMN after experimental sepsis had already been induced in mice rather than giving NMN only before injury.

The authors reported higher tissue NAD+ together with lower lactate, oxidative stress, inflammatory signaling, organ injury, and bacterial burden after NMN. Cardiac, lung, liver, and kidney measures were improved in the reported models, and survival was higher in both short- and longer-term experiments.

Cell experiments suggested that improved macrophage/neutrophil bacterial handling and SIRT3-dependent protection of endothelial mitochondria and barrier function may contribute to the effect. These are animal and cellular findings, not clinical evidence for treating sepsis in people.

Key findings

  • NMN increased NAD+ in septic mouse heart and lung tissue and in several cultured cell types.
  • NMN reduced serum lactate, inflammatory mediators, oxidative-stress markers, and apoptosis-related measures after experimental sepsis.
  • Cardiac dysfunction, lung vascular leakage, liver injury, and kidney dysfunction were attenuated in the reported mouse experiments.
  • NMN reduced blood bacterial burden and improved phagocytic/bactericidal activity of macrophages and neutrophils.
  • Short-term and 30-day survival were improved in the reported sepsis models.
  • In endothelial cells, SIRT3 inhibition offset NMN-associated improvements in mitochondrial, inflammatory, apoptotic, and barrier measures.

Limitations

  • Sepsis was experimentally induced in mice and does not reproduce the heterogeneity of human sepsis.
  • NMN was administered intraperitoneally rather than by routine oral supplementation.
  • The study used high acute doses and model-specific dosing schedules that cannot be converted directly into a clinical regimen.
  • Cell and animal endpoints do not establish efficacy, dosing, or safety in critically ill patients.
  • The proposed SIRT3 mechanism is supported experimentally but does not show that SIRT3 is the only pathway involved.

Funding and transparency

Funding

This study was supported by the Canadian Institute of Health Research (Grant no. PJT-180304 to Tianqing Peng).

Competing interests

The authors declared that they had no competing interests.

HealthspanX observation

This study is disease-model evidence using post-insult treatment, which makes it mechanistically informative but far outside the conditions of routine consumer supplementation.

Interpretive weight

Mechanistic context

Multiple mouse sepsis models and cell experiments showed organ, inflammatory, bacterial-clearance, and survival effects, but the intervention has not been tested as a sepsis therapy in humans.

This record summarizes a publication; it is not medical advice or a claim that a HealthspanX product reproduces the study's results. Report a correction.

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