FOXO1-NMNAT3 axis dysregulation promotes doxorubicin cardiotoxicity: NAD⁺ replenishment as a redox-targeted antioxidant therapy.

ABSTRACT:

Objectives

Doxorubicin (DOX) induces dose-dependent cardiotoxicity, primarily through oxidative stress and metabolic dysregulation. Although NAD⁺ deficiency has been implicated in cardiovascular pathology, its role in DOX-induced cardiotoxicity (DIC) remains poorly understood. This study investigated NAD⁺ metabolism dysregulation as a redox-sensitive mechanism in DIC pathogenesis.

Methods

Human cardiomyocytes (AC16), mouse atrial myocytes (HL-1), and C57BL/6 mice were used to establish the DIC model. The role and mechanism of NAD⁺ in DIC were investigated using a range of methods.

Results

Using integrated in vitro and in vivo models, we demonstrated that DOX induces myocardial oxidative damage accompanied by NAD⁺

SUBMITTER: Cheng F 

PROVIDER: S-EPMC12481541 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature