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

• DOI: 10.1016/j.isci.2024.109163
• Publication Date: 2024-02-13T05:31:31Z
• Authors: Mengjie Xie; Fuding Guo; Lingpeng Song; Wuping Tan; Xinrui Han; Saiting Xu; Xujun Li; Yijun Wang; Yueyi Wang; Liping Zhou; Xiaoya Zhou; Hong Jiang; Lilei Yu
• Keywords: 0301 basic medicine; 0303 health sciences; Science; Immunology; Q; Omics; Article; Cancer

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.