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Nicotinamide Riboside Alleviates Heat Stress-induced Intestinal Barrier Dysfunction in Mice.

Yifan Chen1, Tianzheng Yu1,2

  • 1Consortium for Health and Military Performance, Department of Military and Emergency Medicine, F. Edward Hébert School of Medicine, Uniformed Services University, Bethesda, Maryland.

Shock (Augusta, Ga.)
|May 14, 2025
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Summary

Nicotinamide riboside (NR) protects the intestinal barrier from heat stress by reducing inflammation and oxidative stress. NR pretreatment helps maintain NAD+ homeostasis, preventing heat-induced barrier damage.

Keywords:
ATPHyperthermiaischemiamitochondriamtDNAoxidative stress

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Area of Science:

  • Physiology
  • Molecular Biology
  • Biochemistry

Background:

  • Heat stress impairs intestinal epithelial barrier function.
  • Oxidative stress and inflammation contribute to heat-induced barrier dysfunction.
  • Nicotinamide adenine nucleotide (NAD+) plays a role in redox and inflammatory signaling.

Purpose of the Study:

  • To investigate the protective effects of nicotinamide riboside (NR), an NAD+ precursor, against heat-induced intestinal epithelial barrier injury.
  • To determine if NR can mitigate heat-induced changes in NAD+ metabolism, inflammation, and oxidative stress in the intestine.

Main Methods:

  • Male C57BL/6 J mice were treated with vehicle or NR orally for 10 days.
  • Mice were subjected to a single heat or sham exposure.
  • Intestinal NAD+, NADH levels, NAD+/NADH ratio, IL-6, TNFα, TBARS, mtDNA copy number, and ATP content were measured.

Main Results:

  • NR increased intestinal NAD+ and NADH levels but did not alter the NAD+/NADH ratio.
  • Heat exposure reduced the intestinal NAD+/NADH ratio, impaired barrier function, and increased IL-6, TNFα, and TBARS.
  • NR pretreatment attenuated the negative effects of heat on the intestinal barrier, inflammation, and oxidative stress.
  • NR did not affect heat-induced reductions in mtDNA copy number or ATP content.

Conclusions:

  • Heat stress disrupts intestinal NAD+/NADH homeostasis.
  • NR pretreatment prevents heat-induced intestinal barrier dysfunction by reducing inflammation and oxidative stress.
  • NR's protective effects do not extend to mitigating heat-induced mitochondrial dysfunction.