Protective effect of dimethyl fumarate on oxidative damage and signaling in cardiomyocytes

Kuang,Yuanyuan; Zhang,Yinzhuang; Xiao,Zhen; Xu,Lijun; Wang,Ping; Ma,Qilin

doi:10.3892/mmr.2020.11342

Protective effect of dimethyl fumarate on oxidative damage and signaling in cardiomyocytes

Authors:
- Yuanyuan Kuang
- Yinzhuang Zhang
- Zhen Xiao
- Lijun Xu
- Ping Wang
- Qilin Ma
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Affiliations: Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Department of Cardiovascular Medicine, The First Hospital of Changsha, Changsha, Hunan 410005, P.R. China
Published online on: July 15, 2020 https://doi.org/10.3892/mmr.2020.11342
Pages: 2783-2790
Copyright: © Kuang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Myocardial ischemia/reperfusion (I/R) injury contributes to the pathogenesis of numerous diseases. Based on its antioxidant and anti‑inflammatory effects, dimethyl fumarate (DMF) has been reported to exert protective effects against I/R. However, to the best of our knowledge, its potential role as a myocardial protective agent in heart disease has received little attention. Previous studies have suggested that DMF may exert its protective effects by activating nuclear factor erythroid 2‑related factor 2 (Nrf2); however, the exact underlying mechanisms remain to be elucidated. The aim of the present study was to investigate the protective role of DMF in myocardial I/R injury, and to determine the role of Nrf2 in mediating the activity of DMF. H9c2 cells were incubated with DMF (20 µM) for 24 h before establishing the I/R model, and were then subjected to myocardial ischemia for 6 h, followed by reperfusion. Cell viability, lactate dehydrogenase levels, anti‑oxidant enzyme expression levels and anti‑apoptotic effects were evaluated, and AKT/Nrf2 pathway‑associated mechanisms were investigated. The results of the present study indicated that DMF may reduce myocardial I/R injury in a Nrf2‑dependent manner. DMF significantly improved cellular viability, suppressed the expression of apoptotic markers, decreased the production of reactive oxygen species and increased the expression of Nrf2‑regulated antioxidative genes. Notably, these beneficial DMF‑mediated effects were not observed in the control or I/R groups. In conclusion, the results of the present study suggested that DMF may exert protective effects against a myocardial I/R model, and further validated Nrf2 modulation as a primary mode of action. Thus suggesting that DMF may be a potential therapeutic agent for AKT/Nrf2 pathway activation in myocardial, and potentially systemic, diseases.

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