Effect of simvastatin on passive strain-induced skeletal muscle injury in rats

Introduction: HMG-CoA reductase inhibitors are the most frequently prescribed drugs for treatment of lipid imbalance, but they have side effects, such as myopathy. Our aim was to assess the effect of simvastatin on the inflammatory process induced by skeletal muscle injury. Methods: Rats were divided into experimental groups [control group, simvastatin (20 mg/kg) group, group treated with simvastatin (20 mg/kg) and subjected to injury, and group subjected to injury only]. Histological analysis and analyses of creatine kinase activity and C-reactive protein were performed. Results: Animals treated with simvastatin exhibited significantly greater morphological and structural skeletal muscle damage in comparison to the control group and injured animals without treatment. Conclusions: Although simvastatin has a small anti-inflammatory effect in the early stage after a muscle strain injury, the overall picture is negative, as simvastatin increases the extent of damage to muscle morphology. Further studies are needed. Muscle Nerve 46: 908-913, 2012

Exercise training prevents oxidative stress and ubiquitin-proteasome system overactivity and reverse skeletal muscle atrophy in heart failure

Background: Heart failure (HF) is known to lead to skeletal muscle atrophy and dysfunction. However, intracellular mechanisms underlying HF-induced myopathy are not fully understood. We hypothesized that HF would increase oxidative stress and ubiquitin-proteasome system (UPS) activation in skeletal muscle of sympathetic hyperactivity mouse model. We also tested the hypothesis that aerobic exercise training (AET) would reestablish UPS activation in mice and human HF. Methods/Principal Findings: Time-course evaluation of plantaris muscle cross-sectional area, lipid hydroperoxidation, protein carbonylation and chymotrypsin-like proteasome activity was performed in a mouse model of sympathetic hyperactivity-induced HF. At the 7th month of age, HF mice displayed skeletal muscle atrophy, increased oxidative stress and UPS overactivation. Moderate-intensity AET restored lipid hydroperoxides and carbonylated protein levels paralleled by reduced E3 ligases mRNA levels, and reestablished chymotrypsin-like proteasome activity and plantaris trophicity. In human HF (patients randomized to sedentary or moderate-intensity AET protocol), skeletal muscle chymotrypsin-like proteasome activity was also increased and AET restored it to healthy control subjects' levels. Conclusions: Collectively, our data provide evidence that AET effectively counteracts redox imbalance and UPS overactivation, preventing skeletal myopathy and exercise intolerance in sympathetic hyperactivity-induced HF in mice. Of particular interest, AET attenuates skeletal muscle proteasome activity paralleled by improved aerobic capacity in HF patients, which is not achieved by drug treatment itself. Altogether these findings strengthen the clinical relevance of AET in the treatment of HF.