Table of Contents Author Guidelines Submit a Manuscript
Oxidative Medicine and Cellular Longevity
Volume 2018, Article ID 5179468, 9 pages
Research Article

Inhibition of TRPA1 Attenuates Doxorubicin-Induced Acute Cardiotoxicity by Suppressing Oxidative Stress, the Inflammatory Response, and Endoplasmic Reticulum Stress

Zhen Wang,1,2,3 Menglong Wang,1,2,3 Jianfang Liu,1,2,3 Jing Ye,1,2,3 Huimin Jiang,1,2,3 Yao Xu,1,2,3 Di Ye,1,2,3 and Jun Wan1,2,3

1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
2Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China
3Hubei Key Laboratory of Cardiology, Wuhan 430060, China

Correspondence should be addressed to Jun Wan; moc.621@3691nujnaw

Received 21 September 2017; Revised 6 December 2017; Accepted 18 December 2017; Published 28 February 2018

Academic Editor: Mariateresa Giuliano

Copyright © 2018 Zhen Wang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The transient receptor potential ankyrin 1 (TRPA1) channel is expressed in cardiomyocytes and involved in many cardiovascular diseases. However, the expression and function of TRPA1 in doxorubicin- (Dox-) induced acute cardiotoxicity have not been elucidated. This study aimed at investigating whether blocking the TRPA1 channel with the specific inhibitor HC-030031 (HC) attenuates Dox-induced cardiac injury. The animals were randomly divided into four groups: control, HC, Dox, and Dox + HC. Echocardiography was used to evaluate cardiac function, and the heart was removed for molecular experiments. The results showed that the expression of TRPA1 was increased in the heart after Dox treatment. Cardiac dysfunction and increased serum CK-MB and LDH levels were induced by Dox, but these effects were attenuated by HC treatment. In addition, HC mitigated Dox-induced oxidative stress, as evidenced by the decreased MDA level and increased GSH level and SOD activity in the Dox + HC group. Meanwhile, HC treatment lowered the levels of the proinflammatory cytokines IL-1β, IL-6, IL-17, and TNF-α induced by Dox. Furthermore, HC treatment mitigated endoplasmic reticulum (ER) stress and cardiomyocyte apoptosis induced by Dox. These results indicated that inhibition of TRPA1 could prevent Dox-induced cardiomyocyte apoptosis in mice by inhibiting oxidative stress, inflammation, and ER stress.