Protection against Doxorubicin-Induced Cardiotoxicity through Modulating iNOS/ARG 2 Balance by Electroacupuncture at PC6

• Published in: Oxidative medicine and cellular longevity Vol. 2021; no. 1; p. 6628957
• Main Authors: Wang, Jingya, Yao, Lin, Wu, Xiaoli, Guo, Qi, Sun, Shengxuan, Li, Jie, Shi, Guoqi, Caldwell, Ruth B., Caldwell, R. William, Chen, Yongjun
• Format: Journal Article
• Language: English
• Published: United States Hindawi 2021; Hindawi Limited
• Subjects: Acupuncture; Acupuncture Points; Alcohol; Animals; Antineoplastic Agents - toxicity; Arginase - genetics; Arginase - metabolism; Cardiotoxicity; Cardiotoxicity - etiology; Cardiotoxicity - parasitology; Doxorubicin - toxicity; Ejection fraction; Electroacupuncture; Electroacupuncture - methods; Experiments; Heart; Heart Diseases - etiology; Heart Diseases - prevention & control; Hypertension; Ischemia; Laboratories; Male; Mice; Mice, Inbred C57BL; Myocardium - metabolism; Nitric oxide; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - metabolism; Signal Transduction; China
• ISSN: 1942-0900; 1942-0994
• DOI: 10.1155/2021/6628957

Background. Doxorubicin (DOX) is a commonly used chemotherapeutic drug but is limited in clinical applications by its cardiotoxicity. Neiguan acupoint (PC6) is a well-recognized acupoint for the treatment of cardiothoracic disease. However, whether acupuncture at PC6 could be effective in preventing DOX-induced cardiotoxicity is still unknown. Methods. A set of experiments were performed with myocardial cells, wild type, inducible nitric oxide synthase knockout (iNOS-/-), and myocardial-specific ablation arginase 2 (Myh6-ARG 2-/-) mice. We investigated the protective effect and the underlying mechanisms for electroacupuncture (EA) against DOX-induced cardiotoxicity by echocardiography, immunostaining, biochemical analysis, and molecular biotechnology in vivo and in vitro analysis. Results. We found that DOX-mediated nitric oxide (NO) production was positively correlated with the iNOS level but has a negative correlation with the arginase 2 (ARG 2) level in both myocardial cells and tissues. Meanwhile, EA at PC6 alleviated cardiac dysfunction and cardiac hypertrophy in DOX-treated mice. EA at PC6 blocked the upregulation of NO production in accompanied with the downregulated iNOS and upregulated ARG 2 levels in myocardial tissue induced by DOX. Furthermore, knockout iNOS prevented cardiotoxicity and EA treatment did not cause the further improvement of cardiac function in iNOS-/- mice treated by DOX. In contrast, deficiency of myocardial ARG 2 aggravated DOX-induced cardiotoxicity and reduced EA protective effect. Conclusion. These results suggest that EA treatment at PC6 can prevent DOX-induced cardiotoxicity through modulating NO production by modulating the iNOS/ARG 2 balance in myocardial cells.