Sulforaphane alleviates muscular dystrophy in mdx mice by activation of Nrf2

Sulforaphane (SFN), one of the most important isothiocyanates in the human diet, is known to have chemo-preventive and antioxidant activities in different tissues via activation of nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated induction of antioxidant/phase II enzymes, such as heme oxygenase-1 and NAD(P) H quinone oxidoreductase 1. However, its effects on muscular dystrophy remain unknown. This work was undertaken to evaluate the effects of SFN on Duchenne muscular dystrophy. Four-week-old mdx mice were treated with SFN by gavage (2 mg.kg body wt(-1).day(-1) for 8 wk), and our results demonstrated that SFN treatment increased the expression and activity of muscle phase II enzymes NAD(P) H quinone oxidoreductase 1 and heme oxygenase-1 with a Nrf2-dependent manner. SFN significantly increased skeletal muscle mass, muscle force (similar to 30%), running distance (similar to 20%), and GSH-to-GSSG ratio (similar to 3.2-fold) of mdx mice and decreased the activities of plasma creatine phosphokinase (similar to 45%) and lactate dehydrogenase (similar to 40%), gastrocnemius hypertrophy (similar to 25%), myocardial hypertrophy (similar to 20%), and malondialdehyde levels (similar to 60%). Furthermore, SFN treatment also reduced the central nucleation (similar to 40%), fiber size variability, and inflammation and improved the sarcolemmal integrity of mdx mice. Collectively, these results show that SFN can improve muscle function and pathology and protect dystrophic muscle from oxidative damage in mdx mice associated with Nrf2 signaling pathway, which indicate Nrf2 may have clinical implications for the treatment of patients with muscular dystrophy.