Nicotinamide Riboside Improves Autophagic Flux And Prevents Doxorubicin-Induced Cardiac Injury

Introduction: Doxorubicin is widely used as a first-line chemotherapeutic drug for various malignancies. However, doxorubicin causes severe cardiotoxicity. Recent studies report that autophagic flux is impaired and contributes to doxorubicin-induced cardiac injury. Nicotinamide riboside (NR) is a precursor of NAD+, a co-factor required for Sirt1 activity. Activation of Sirt1 improves autophagic flux. However, the effects of NR have never been reported in doxorubicin-induced cardiac injury. Hypothesis: NR prevents doxorubicin-induced cardiac injury through Sirt1-mediated improvement of autophagic flux. Methods: Cardiac injury was induced in mice by injection of doxorubicin (20 mg/kg, i.p.). NR (300 mg/kg, i.p.) was given 30 min before doxorubicin injection. Myocardial function was assessed by echocardiography 5 days after doxorubicin injection. Cultured cardiomyocytes were incubated with NR followed by doxorubicin (1 μmol/L) for 24 hours. Apoptosis, autophagy and reactive oxygen species (ROS) were analyzed...