The

mechanism of action is also rather complex, including increased level of glutathione and inhibition of the transcription of proinflammatory and pro-oxidative pathways. Importantly, ROS also act by activating NF-kB. Green tea extracts and other natural anti-oxidant, such as curcumin and genistein have been reported to reduce Inhibitors,research,lifescience,medical NFkB activation; this has been claimed to play an important role in the potential benefit in mdx mice, although controversial results are present in the literature (41-43). Resveratrol has been also tested for its potential antioxidant effects. Hori et al., described the ability of this sirtuin 1 activator to reduce the markers of oxidative stress and the expression of NOX subunits (44); in parallel we found that resveratrol can reduce the O2 – in muscles of exercised mdx mice, Inhibitors,research,lifescience,medical while enhancing exercise performance and decreasing histological and biochemical markers of damage (unpublished observation). The ability of BN82270, a dual compound with anti-oxidant and anti-calpain Inhibitors,research,lifescience,medical activity, to contrast some pathology signs in the mdx mice, such as exerciseinduced weakness and the high plasma CK, can be likely due to the anti-oxidant moiety, also in AMD3100 relation to the less relevant role of calpain proteases in the pathology (45). Anabolic drugs The possibility of increasing

muscle mass and consequently muscle strength by anabolic drugs seems a reasonable

approach Inhibitors,research,lifescience,medical for a muscle wasting disorder such as DMD. Nonetheless this is one of the most widely trialed therapeutic strategies and include drugs acting via different mechanisms, such as anabolic steroids, myostatin-blocking antibodies and β2-adrenoceptor Inhibitors,research,lifescience,medical agonists (β2-agonists). However, controversial results have been obtained, leading to possible concern that enlargement of muscle fiber size may in fact lead to make fibers more susceptible to contraction-induced injury, since larger type II fibers are more preferentially affected in dystrophic muscles. This hypothesis has been recently rejected by Lynch’s group using the muscle specific β2-agonist formeterol. Its anabolic action is associated with an enhanced protein synthesis not and decreased calpain activity and in mdx mice it increases muscle mass and fiber size as well as force (46-48). This drug can be of value due to the less cardiac side effects with respect to classical β2- agonists, which however gave controversial results in both dystrophic patients and mice (see 12). Anabolic steroids, including both testosterone and nandrolone, also gave controversial results and a tendency to increase muscle fiber degeneration has been observed (49). No clear benefit or mechanism of action have been described in mdx mice treated with anabolic steroids and this may in part account for the controversial results in DMD patients (50).