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

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.