Noninvasive neuromodulation protects against doxorubicin-induced cardiotoxicity and inhibits tumor growth

• Published in: iScience Vol. 27; no. 3; p. 109163
• Main Authors: Xie, Mengjie, Guo, Fuding, Song, Lingpeng, Tan, Wuping, Han, Xinrui, Xu, Saiting, Li, Xujun, Wang, Yijun, Wang, Yueyi, Zhou, Liping, Zhou, Xiaoya, Jiang, Hong, Yu, Lilei
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.03.2024; Elsevier
• Subjects: Cancer; Immunology; Omics; Immunology; Omics; Cancer
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2024.109163

Doxorubicin (Dox) poses a considerable threat to patients owing to its cardiotoxicity, thus limiting its clinical utility. Optimal cardioprotective intervention strategies are needed to suppress tumor growth but also minimize cardiac side effects. Here, we showed that tragus vagus nerve stimulation (tVNS) improved the imbalanced autonomic tone, ameliorated impaired cardiac function and fibrosis, attenuated myocyte apoptosis, and mitochondrial dysfunction compared to those in the Dox group. The beneficial effects were attenuated by methyllycaconitine citrate (MLA). The transcript profile revealed that there were 312 differentially expressed genes and the protection of tVNS and retardation of MLA were related to inflammatory response and NADPH oxidase activity. In addition, tVNS synergizing with Dox inhibited tumor growth and lung metastasis and promoted apoptosis of tumor cells in an anti-tumor immunity manner. These results indicated that non-invasive neuromodulation can play a dual role in preventing Dox-induced cardiotoxicity and suppressing tumor growth through inflammation and oxidative stress. [Display omitted] •The tVNS plays a dual role in preventing cardiotoxicity and suppressing tumor growth•These effects are mediated through the α7nAchR pathway•Inflammatory response and NADPH oxidase activity are the potential mechanisms•This study provides a promising candidate for cardiovascular and cancer patients Immunology; Cancer; Omics