Nicotinamide riboside: A new promising therapy for my syndrome management

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Strong evidence has demonstrated a link between acute myocardial infarction (MI) and the subsequent decline in cardiac output and acute kidney injury (AKI). A decrease in cardiac and renal nicotinamide adenine dinucleotide (NAD) has been reported post-cardiac and kidney diseases. NAD is a major coenzyme for energy metabolism and a signaling molecule used by the Sirtuins (e.g. SIRT1) and polyADPribose polymerases (e.g. PARP1) involved in the regulation of energy metabolism, cell survival. The correlation between myocardial and kidney NAD homeostasis in the context of MI-induced AKI and the potential beneficial impact of NAD boosting therapies in this disease model, however, are yet to be determined. We aim at evaluating the renal protective effects of nicotinamide riboside (NR), a precursor of NAD, used by salvage enzymes renal NMRK1 and cardiac NMRK2, in an MI mouse model. Male mice were divided into four groups: Sham + Vehicle, Sham + NR, MI + Vehicle, and MI + NR. NR was administered by intraperitoneal injection for 4 days (D) post-MI. Echocardiography was performed and kidneys were evaluated at the structural, molecular, and functional levels, including mitochondrial respiration. Myocardial NAD levels significantly decreased at D4 post-MI when compared to the SHAM groups while they were maintained in MINR group. Renal NAD levels remained unchanged at D4 post-MI, whereas, NR administration doubled NAD levels compared to the SHAM groups. Hemodynamic analysis revealed a comparable decrease in ejection fraction and cardiac output post-MI in the presence and absence of NR treatment. Urine output decreased in mice 4D post-MI, whereas it remained unchanged following NR. Kidney morphological alterations characterized by fibrosis and cell death markedly increased 4D post-MI, whereas NR treatment reverses these alterations. No significant change in nicotinamide phosphorybosil transferase mRNA expression levels in mice 4D post-MI was observed, whereas NR administration increased its levels. No substantial alteration in mitochondrial function in terms of the activity of complex I, II and IV was seen 4D post-MI in permeabilized renal cortex tissue. Cell death occurred at 4D post MI in the kidneys as evaluated by TUNEL staining and NR treatment reduced this level by 30%. NR supplementation appears as a potential promising therapy for MI-induced AKI. NR may act more toward survival signaling pathways than mitochondrial respiration.