Cardiac and skeletal muscle changes associated with rosuvastatin therapy in dystrophic mdx mice

Statins are prescribed to prevent and treat atherosclerotic cardiovascular and metabolic diseases but have controversial effects on skeletal muscles. While statins are a reported cause of myopathy, some studies have suggested that statins could potentially ameliorate dystrophy due to their pleiotropic effects on inflammation, myonecrosis, and autophagy. In the present study, we evaluated the potential benefit of rosuvastatin treatment on heart, limb, and diaphragm muscles in dystrophin-deficient mdx mice at an early stage (45 days of age) of disease. Mdx mice received rosuvastatin (10 mg/kg) by gavage for 30 days beginning at 15 days of age. Normal C57BL/10 mice received rosuvastatin by the same route over the same interval. In the mdx group, rosuvastatin significantly increased IgG-positive fibers (myonecrosis) and the inflammatory areas in the biceps brachii and diaphragm muscles and decreased the anterior limb muscle force (grip strength). Molecular markers of inflammation (TNF-α and NF-kB) and fibrosis (fibronectin) were not altered by rosuvastatin in mdx mice skeletal and cardiac muscles. In normal mice, rosuvastatin increased CK, TNF-α (heart), NF-kB (diaphragm), and fibronectin (heart and diaphragm). Inflammatory areas were seen in all normal muscles of rosuvastatin-treated mice. Rosuvastatin did not benefit dystrophy in the mdx mice and was associated with inflammation in normal cardiac and skeletal muscles.