Nicotinamide riboside promotes autolysosome clearance in preventing doxorubicin-induced cardiotoxicity

This study investigated whether nicotinamide riboside, a precursor of NAD+, prevents doxorubicin cardiotoxicity by improving autophagic flux. We report that administration of nicotinamide riboside elevated NAD+ levels, and reduced cardiac injury and myocardial dysfunction in doxorubicin-injected mice. These protective effects of nicotinamide riboside were recapitulated in cultured cardiomyocytes upon doxorubicin treatment. Mechanistically, nicotinamide riboside prevented the blockage of autophagic flux, accumulation of autolysosomes and oxidative stress in doxorubicin-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 nicotinamide riboside during doxorubicin-induced cardiotoxicity. Collectively, our study shows that nicotinamide riboside enhances autolysosome clearance via the NAD+/SIRT1 signaling thereby preventing doxorubicin-triggered cardiotoxicity.

Source: Clinical Science - July 1, 2019 Category: Biomedical Science Authors: Zheng, D., Zhang, Y., Zheng, M., Cao, T., Wang, G., Zhang, L., Ni, R., Brockman, J., Zhong, H., Fan, G.-C., Peng, T. Tags: PublishAheadOfPrint Source Type: research