Although
statins are prescribed as relatively safe and effective drugs for hypercholesterolemic patients, it has been reported that a significant side effect,
myopathy, occurs infrequently during medication. Moreover, because
statins decrease cardiac
ubiquinone levels, the risk of cardiac dysfunction has been suggested. This study sought to evaluate and compare the cytotoxicity of
statins (
cerivastatin,
pitavastatin,
fluvastatin,
simvastatin,
atorvastatin and
pravastatin) in cultured human skeletal muscle cells (HSkMCs) and the effects on
ubiquinone levels in
statin-treated rat skeletal muscle and heart.
Cerivastatin, the most potent inhibitor of
HMG-CoA reductase, showed the strongest cytotoxicity (over 10-fold) among the
statins examined, while the effects of the others were in a similar range. In rat experiments, neither
pitavastatin nor
cerivastatin decreased
ubiquinone levels in skeletal muscle, but both dose-dependently lowered
ubiquinone levels in the heart. As the rates of reduction by
pitavastatin (9.6% at 30 mg/kg) and
cerivastatin (9.7% at 0.3 mg/kg) were almost equal, it was estimated that
cerivastatin reduced
ubiquinone levels in the rat heart approximately 100-fold more strongly than
pitavastatin, based on the effective doses. We found that
cerivastatin showed the most potent cytotoxicity in HSkMCs and strongly lowered
ubiquinone levels in the rat heart.