Nicotinamide mononucleotide supplementation ameliorates testicular damage induced by ischemia-reperfusion through reshaping macrophage and neutrophil inflammatory properties

BACKGROUND: Ischemia-reperfusion (I/R) injury is the main pathophysiology of testicular torsion-detorsion (T/D). However, there is no safe and effective treatment for testicular I/R injury. METHODS: , Malondialdehyde (MDA), and superoxide dismutase (SOD) were evaluated. The markers of testicular function, including sperm quality, testosterone secretion, and the number of germ cells, were compared between groups. The reactive oxygen species (ROS), apoptosis, and immune cells were analyzed by flow cytometry. The expression of inflammatory genes, germ cell markers, and the phosphorylation of p65 and STAT3 were assessed by qRT-PCR, immunofluorescence, and western blot, respectively. RESULTS: content, increase serum testosterone levels, prevent Leydig cell and germ cell injury, and improve sperm quantity. Mechanistically, NMN supplementation relieved the sharply hostile immune microenvironment. Specifically, NMN supplementation could mitigate the oxidative stress and cell apoptosis in the I/R injured testes, downregulate the protein expression of p-p65 and p-STAT3 in inflammatory pathways, limit the excessive activation of inflammatory responses in testicular tissues, and reshape the inflammatory properties of macrophages and neutrophils. CONCLUSIONS: may be a promising and safe strategy to improve clinical outcomes in I/R-induced testicular damage.