Nicotinamide riboside prevented doxorubicin-induced cardiotoxicity in mice and cultured cardiomyocytes by enhancing autolysosome clearance via NAD+/SIRT1 signaling.
Does nicotinamide riboside prevent doxorubicin-induced cardiotoxicity in mice and cultured cardiomyocytes?
Nicotinamide riboside protects against doxorubicin-induced cardiotoxicity by enhancing autolysosome clearance via NAD+/SIRT1 signaling in preclinical models.
Abstract Doxorubicin (DOX) is widely used as a first-line chemotherapeutic drug for various malignancies. However, DOX causes severe cardiotoxicity, which limits its clinical uses. Oxidative stress is one of major contributors to DOX-induced cardiotoxicity. While autophagic flux serves as an important defense mechanism against oxidative stress in cardiomyocytes, recent studies have demonstrated that DOX induces the blockage of autophagic flux, which contributes to DOX cardiotoxicity. The present study investigated whether nicotinamide riboside (NR), a precursor of nicotinamide adenine dinucleotide (NAD)+, prevents DOX cardiotoxicity by improving autophagic flux. We report that administration of NR elevated NAD+ levels, and reduced cardiac injury and myocardial dysfunction in DOX-injected mice. These protective effects of NR were recapitulated in cultured cardiomyocytes upon DOX treatment. Mechanistically, NR prevented the blockage of autophagic flux, accumulation of autolysosomes, and oxidative stress in DOX-treated cardiomyocytes, the effects of which were associated with restoration of lysosomal acidification. Furthermore, inhibition of lysosomal acidification or SIRT1 abrogated these protective effects of NR during DOX-induced cardiotoxicity. Collectively, our study shows that NR enhances autolysosome clearance via the NAD+/SIRT1 signaling, thereby preventing DOX-triggered cardiotoxicity.
Zheng et al. (Mon,) conducted a other in Doxorubicin-induced cardiotoxicity. Nicotinamide riboside was evaluated on Cardiac injury and myocardial dysfunction. Nicotinamide riboside prevented doxorubicin-induced cardiotoxicity in mice and cultured cardiomyocytes by enhancing autolysosome clearance via NAD+/SIRT1 signaling.