Nicotinamide riboside alleviates heat stress-induced intestinal barrier dysfunction in mice

Heat stress can damage the intestinal epithelial barrier, leading to harmful substances entering the body. Although oxidative stress and inflammation are implicated in heat-induced intestinal barrier dysfunction, the protective effect of anti-inflammatory and antioxidant agents on the intestinal epithelial barrier against heat insult remains inconsistent. Evidence suggests that nicotinamide adenine nucleotide (NAD⁺) is a central signaling molecule in the regulation of redox and inflammatory reactions. In this study, we examined the effects of the NAD⁺ precursor nicotinamide riboside (NR) on heat-induced intestinal epithelial barrier injury. Male C57BL/6 J mice were orally administered vehicle or NR for 10 days and subsequently were subjected to a single heat or sham exposure test. NR significantly increased intestinal NAD⁺ and NADH levels but did not change the NAD⁺/NADH ratio in both sham and heat-exposed mice. Heat-exposed mice reduced intestinal NAD⁺/NADH ratio, caused intestinal barrier impairment and dysfunction, and increased intestinal IL-6, TNFα and TBARS levels. NR reduced these effects of heat exposure. Heat also reduced mtDNA copy number and ATP content in the intestinal tissue, but NR did not impact these changes. Heat stress disrupts intestinal NAD⁺/NADH homeostasis and NR pretreatment prevents this effect. The protective effect of NR on mouse intestinal barrier against heat is associated with reduced inflammation and oxidative stress. However, NR has no effect on heat-induced intestinal mitochondrial dysfunction.