Inhibition of NETs prevents doxorubicin-induced cardiotoxicity by attenuating IL-18-IFN-γ-Cx43 axis induced cardiac conduction abnormalities.

Doxorubicin-induced cardiotoxicity (DIC) is one of the most severe side effects of doxorubicin, yet the underlying mechanisms remain incompletely understood. Our results showed that Neutrophil extracellular traps (NETs) accumulated in plasma and cardiac tissue after doxorubicin treatment. The inhibition of NETs formation by Pad4 gene ablation significantly attenuated doxorubicin-induced arrhythmia, prolonged survival time and reduced the levels of Troponin T (cTnT) and creatine kinase MB (CK-MB) in mice.