Background: Doxorubicin (DOX), an anti-cancer drug, induces cardiotoxicity and skeletal muscle atrophy. We recently reported that resveratrol, an activator of NAD⁺-dependent deacetylase SIRT1, prevented DOX-induced cardiotoxicity. In this study, we examined effects of nicotinamide mononucleotide (NMN), a precursor of NAD⁺, on DOX-induced cardiotoxicity and skeletal muscle atrophy.
Methods: Male mice were randomly divided into three groups: vehicle, DOX, and NMN+Dox groups. In the DOX group, mice received DOX (5 mg/kg, IP) once a week for four times. NMN (500 mg/kg, IP) was administered to mice in the NMN+DOX group 30 min before and 2 days after DOX injection. Echocardiography was performed at 1 week after the final DOX injection. Heart weight and tibialis anterior (TA) muscle weight were measured at 1 week after final DOX.
Results: Body weight was gradually decreased in the DOX group compared with the vehicle group. NMN partially blocked the decrease in body weight by DOX. Left ventricular fractional shortening (FS), an index of cardiac contraction, was lower in the DOX group than the vehicle group but was preserved in the NMN+DOX group. Heart weight-to-tibia length (TL) ratio and TA weight-to-TL ratio were lower in the DOX group, indicating myocardial and skeletal muscle atrophy by DOX. NMN treatment blocked the reductions heart weight and TA weight induced by DOX.
[Conclusion] These findings suggest that supplementation of NAD⁺ by administration of NMN could be a therapeutic strategy for prevention of cardiotoxicity and skeletal muscle atrophy induced by DOX.