Key result
Nicotinamide riboside dose-dependently attenuates doxorubicin cardiotoxicity by improving autolysosome clearance.
Why the study?
Doxorubicin causes severe cardiotoxicity by blocking autophagic flux, prompting investigation into whether nicotinamide riboside prevents this cardiotoxicity by improving autophagic flux.
Does nicotinamide riboside prevent doxorubicin-induced cardiotoxicity in mouse models and isolated cardiomyocytes?
Does nicotinamide riboside prevent doxorubicin-induced cardiotoxicity in mouse models and isolated cardiomyocytes?
Nicotinamide riboside, a commercially available NAD+ precursor, shows significant promise in preclinical models for preventing doxorubicin-induced cardiotoxicity by restoring autophagic flux.
NR may protect against doxorubicin cardiotoxicity in mice; hypothesis-generating and should not change practice pending human trials.
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.
No takes yet. Share an insight, caveat, or question.
Zheng et al. (2019) studied Doxorubicin-induced cardiotoxicity. Nicotinamide riboside vs. Saline or vehicle was evaluated on Cardiac injury, myocardial dysfunction, and autophagic flux. Nicotinamide riboside dose-dependently attenuated doxorubicin-induced myocardial dysfunction and cardiac injury by enhancing autolysosome clearance via NAD+/SIRT1 signaling.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: