Nicotinamide riboside: A promising therapy for MI-induced acute kidney injury by upregulating nicotinamide phosphoribosyltransferase-mediated NAD levels
Nicotinamide riboside: A promising therapy for MI-induced acute kidney injury by upregulating nicotinamide phosphoribosyltransferase-mediated NAD levels
HABEICHI, N. J.; Amin, G.; Boitard, S. E.; Tannous, C. J.; Ghali, R.; MOMKEN, I.; Diab, R.; Booz, G. W.; Mericskay, M.; Zouein, F. A.
AbstractBackground: Cardiorenal syndrome (CRS) type 1 is characterized by the development of acute kidney injury (AKI) following acute cardiac illness and notably acute myocardial infarction (MI). AKI is considered an independent risk factor increasing mortality rate substantially. Nicotinamide dinucleotide (NAD) is an important coenzyme in energy metabolism and oxidative phosphorylation and in its oxidized form, a substrate for multiple NAD+-dependent enzymes such as Sirtuins and poly-ADP ribose polymerases. Decreased cardiac NAD levels along with a down-regulation of the nicotinamide phosphoribosyl transferase (NAMPT) have been reported following MI. A compensatory upregulation in nicotinamide riboside kinase (NMRK) 2, an NAD+ biosynthetic enzyme that uses nicotinamide riboside (NR) to generate NAD+ takes place in the heart after MI but the impact on kidney NAD metabolism and function has not been addressed before. Methods: MI was induced by ligating the left anterior descending coronary artery in 2 months old C57BL6/J mice, followed by the administration of NR (IP injection, 400mg/kg/day) for four and seven days. We hypothesized that NR treatment could be a potential promising therapy for MI-induced AKI. Results: Our findings showed no significant improvement in cardiac ejection fraction following NR treatment at days 4 and 7 post-MI, whereas kidney functions were enhanced and morphological alterations and cell death decreased. The observed renal protection seems to be mediated by an up-regulation of NAMPT-mediated increase in renal NAD levels, notably in distal tubules. Conclusion: Our findings indicate that NR could be a potential promising therapy for AKI following an early stage of MI.