Abstract
Background
Statins therapy is effective in the prevention of cardiovascular events. However, its use is associated with skeletal muscle myopathy, which may be severe enough to discontinue statin therapy, thus exposing patients to more morbidity and mortality. This study was conducted to assess the effect of L-carnitine on the skeletal muscle contractility in a rat model of statin-induced myopathy and to clarify its possible mechanisms.
Methods
Twenty-one female Sprague Dawley rats were used throughout this study. The rats were divided into the normal control group, statin-induced myopathy group and statin/L-carnitine-treated group. The assessment of gastrocnemius muscle contractility, plasma creatine kinase (CK) levels and oxidative stress markers (malondialdehyde, reduced glutathione) was also carried out done.
Results
The results of the current study suggest that simvastatin decreased the skeletal muscle mass and altered the muscle contractile properties. It also significantly increased plasma CK level and induced a state of oxidative stress state (high MDA, low GSH). Meanwhile, concurrent L-carnitine significantly reduced statin-induced myopathy and improved the oxidative stress markers and skeletal muscle contractile parameters.
Conclusions
Statin myopathy is postulated to be due to mitochondrial dysfunction, cellular oxidative stress, induction of apoptosis, reduction in the expression of chloride channel and its related conductance, in addition to the alteration of Ca2+ homeostasis. L-carnitine has an antioxidant effect, reduces skeletal muscle atrophy and improves the skeletal muscle contractility in simvastatin-induced myopathy.
Ketogenic diet increases mitochondria volume in the liver and skeletal muscle without altering oxidative stress markers in rats