Prooxidative toxicity and selenoprotein suppression by cerivastatin in muscle cells

Area of Science:

• Biochemistry
• Molecular Biology
• Pharmacology

Background:

• Statins are widely prescribed for hypercholesterolemia.
• Despite a good safety profile, statins can cause myotoxicity.
• The molecular basis for statin-induced myotoxicity is not fully understood.

Purpose of the Study:

• To investigate the molecular mechanisms underlying statin-induced myotoxicity.
• To explore the effect of statins on selenoprotein synthesis in muscle cells.
• To determine if statin myotoxicity is linked to oxidative stress vulnerability.

Main Methods:

• Cultured myoblasts and skeletal muscle cells were treated with statins (cerivastatin, atorvastatin).
• Selenoprotein synthesis, cellular oxidative stress resistance, and levels of specific selenoproteins (GPx1, SelN) were assessed.
• Effects of selenite, ebselen, ubiquinone, and mevalonic acid on statin-treated cells were evaluated.

Main Results:

• Cerivastatin, at nanomolar concentrations, inhibited selenoprotein synthesis and increased oxidative stress vulnerability in muscle cells.
• Atorvastatin showed similar effects but at higher concentrations.
• Mevalonic acid prevented statin-induced decreases in peroxide resistance, while selenite, ebselen, and ubiquinone did not fully counteract the effects.

Conclusions:

• Statin-induced suppression of essential antioxidant selenoproteins may explain their myotoxic potential.
• Muscle cells are particularly susceptible to statin-induced impairment of selenoprotein synthesis.
• This finding provides a molecular explanation for adverse muscular side-effects associated with statin use.