Low dose simvastatin induces compositional, structural and dynamic changes in rat skeletal extensor digitorum longus muscle tissue

Abstract

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.

Structural effects of simvastatin on rat liver tissue: Fourier transform infrared and Raman microspectroscopic studies

“…Although the C─H stretching region contains a weak band which mainly originates from proteins (CH 3 symmetric stretching band), the C─H region are generally attributed to mainly lipids. 6,32 The amide I/amide II ratio was calculated by dividing the area under the amide I band to that of amide II band which indicates variation in protein structure. 6,32,38 Nucleic acid to protein ratio was also calculated from the ratios of the band area of specific DNA and/or general nucleic acid band to the area of protein amide II band.…”

“…6,32 The amide I/amide II ratio was calculated by dividing the area under the amide I band to that of amide II band which indicates variation in protein structure. 6,32,38 Nucleic acid to protein ratio was also calculated from the ratios of the band area of specific DNA and/or general nucleic acid band to the area of protein amide II band. FTIR microspectroscopic results were expressed as representative color-coded images for each of these spectral parameters.…”

“…Our group previously reported that lower dose (20 mg∕kg∕day) has less side effects than high doses (50 mg∕kg∕day) in skeletal muscle. 6,7 Higher doses (160 mg) have been found to be too toxic, and perceived as overdose while giving only minimal benefit in terms of lipid lowering. 8 The pleiotropic effects that are the beneficial effects beyond cholesterol lowering of statins have been previously investigated in clinical studies.…”

“…In recent years, the pleiotropic and adverse effects of simvastatin on molecular composition and structure of bone 13,14 and muscle 6,7,14 tissues have been studied by our group using FTIR transmission and attenuated total reflectance (ATR)-FTIR spectroscopic techniques. In one of these studies, we reported simvastatin-induced relative protein secondary structural changes on soft tissues (liver, testis, and sciatic nerve) and hard tissues (femur and tibia) by applying neural network approach on well-known amide I protein band (1700 to 1600 cm −1 ) acquired by ATR-FTIR spectroscopy.…”

Molecular approach to the chemical characterization of fish-exuded kairomone: a Fourier transform infrared spectroscopic study

“…Therefore, the attained data is a clear representation of the relative differences between treatments. It can safely be said that it was possible to deduce relative information during this study with dry samples Simsek Ozek et al 2009). …”