Boosting cellular NAD+ concentration with nicotinamide mononucleotide prevents Doxorubicin-induced cardiotoxicity
Abstract
Doxorubicin (DOX) is a powerful chemotherapy that functions by interfering with cancer cells’ growth. However, the use of DOX is limited due to its detrimental side effects that can lead to serious cardiovascular complications. Our goal is to determine if nicotinamide mononucleotide (NMN) and histone acetyltransferase (HAT) inhibitors can protect against DOX-induced cardiotoxicity. Our findings revealed that DOX reduced NAD+ concentration and induced damage to H9c2 cells as evidenced by higher caspase-3 activity and lactate dehydrogenase release. Pre-incubation with NMN increased NAD+ concentration and attenuated DOX-induced damage. There was higher cell viability in the NMN pre-incubated group compared to the vehicle treated group in response to DOX. Furthermore, mice pre-treated with NMN had higher ejection fraction and fraction shortening percentage compared to the vehicle treated group. In contrast, pre-incubation with HAT inhibitors failed to protect DOX-treated cells. Thus, our study suggests that NMN may be a potential drug that prevents DOX-induced cardiotoxicity.