Low dose simvastatin induces compositional, structural and dynamic changes in rat skeletal extensor digitorum longus muscle tissue.
Statins are commonly used drugs in the treatment of hypercholesterolaemia. There are many adverse effects of statins on skeletal muscle, but the underlying mechanisms remain unclear. In the present study, the effects of low dose (20 mg/kg) simvastatin, a lipophilic statin, on rat EDL muscle (extensor digitorum longus muscle) were investigated at the molecular level using FTIR (Fourier-transform infrared) spectroscopy. FTIR spectroscopy allows us rapid and sensitive determination of functional groups belonging to proteins, lipids, carbohydrates and nucleic acids simultaneously. The results revealed that simvastatin treatment induces a significant decrease in lipid, nucleic acid, protein and glycogen content. A significant increase in the lipid/protein and nucleic acid/protein ratios was also obtained with simvastatin treatment. Furthermore, an increase in lipid order and membrane fluidity was detected. A decrease in the bandwidth of the amide I band and shifting of the position of this band to higher frequency values in treated muscle indicates structural changes in proteins. Detailed secondary structure analysis of the amide I band revealed a significant increase in antiparallel and aggregated beta-sheet, random coil structure and a significant decrease in beta-sheet structure, which indicates protein denaturation.
Simsek Ozek
Nihal
N
Department of Biological Sciences, Middle East Technical University, 06531 Ankara, Turkey.
Sara
Yildirim
Y
Onur
Rustu
R
Severcan
Feride
F
D000818:Animals; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005583:Fourier Analysis; D006003:Glycogen / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000633:toxicity*; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D009124:Muscle Proteins / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D009135:Muscular Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D009696:Nucleic Acids / Q000187:drug effects / Q000378:metabolism; D011489:Protein Denaturation / Q000187:drug effects; D055550:Protein Stability / Q000187:drug effects; D017433:Protein Structure, Secondary / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000633:toxicity*; D013055:Spectrophotometry, Infrared
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009124:Muscle Proteins; D009696:Nucleic Acids; D006003:Glycogen; D019821:Simvastatin