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

Ozek Simsek, Nihal
Sara, Yildirim
Onur, Rustu
Severcan, Feride
<jats:p>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 β-sheet, random coil structure and a significant decrease in β-sheet structure, which indicates protein denaturation.</jats:p>
Bioscience Reports


Structural and functional characterization of simvastatin-induced myotoxicity in different skeletal muscles
Ozek, Nihal Simsek; Bal, I. Burak; SARA, MEHMET YILDIRIM; Onur, Rustu; Severcan, Feride (Elsevier BV, 2014-01-01)
Background: Statins are the most commonly used drugs for the treatment of hypercholesterolemia. Their most frequent side effect is myotoxicity. To date, it remains unclear whether statins preferentially induce myotoxicity in fast- or in slow-twitch muscles. Therefore, we investigated these effects on fast- (extensor digitorum longus; EDL), slow- (soleus; SOL), and mixed-twitch muscles (diaphragm; DIA) in rats by comparing their contractile and molecular structural properties.
Interaction of the cholesterol reducing agent simvastatin with zwitterionic DPPC and charged DPPG phospholipid membranes
Sariisik, Ediz; KOÇAK, MUSTAFA; Baloglu, Fatma Kucuk; Severcan, Feride (Elsevier BV, 2019-04-01)
Simvastatin is a lipid-lowering drug in the pharmaceutical group statins. Interaction of a drug with lipids may define its role in the system and be critical for its pharmacological activity. We examined the interactions of simvastatin with zwitterionic dipalmitoyl phosphatidylcholine (DPPC) and anionic dipalmitoyl phosphatidylglycerol (DPPG) multilamellar vesicles (MLVs) as a function of temperature at different simvastatin concentrations using Fourier transform infrared (FTIR) spectroscopy and differentia...
Drug repositioning as an effective therapy for protease-activated receptor 2 inhibition
Saqib, Uzma; Savai, Rajkumar; Liu, DongFang; Banerjee, Sreeparna; Baig, Mirza S. (Wiley, 2019-02-01)
Proteinase-activated receptor 2 (PAR-2) is a G protein-coupled receptor activated by both trypsin and a specific agonist peptide, SLIGKV-NH2. It has been linked to various pathologies, including pain and inflammation. Several peptide and peptidomimetic agonizts for PAR-2 have been developed exhibiting high potency and efficacy. However, the number of PAR-2 antagonists is smaller. We screened the Food and Drug Administration library of approved compounds to retrieve novel antagonists for repositioning in the...
Modulation of human flavin-containing monooxygenase 3 activity by tricyclic antidepressants and other agents: Importance of residue 428
Adalı, Orhan; Philpot, RM (Elsevier BV, 1998-10-01)
Human flavin-containing monooxygenase 3 (FMO3) is subject to modulation by tricyclic antidepressants and other agents. Imipramine activates FMO3-catalyzed metabolism of methimazole at all substrate concentrations tested. This distinguishes FMO3 from rabbit FMO1 and FMO2, which are activated at high substrate concentration and inhibited at low substrate concentration, and pig FMO1, which is inhibited at all substrate concentrations. The response of FMO3 is also unique in that chlorpromazine is markedly more ...
15-lipoxygenase-1 exerts its tumor suppressive role by inhibiting nuclear factor-kappa B via activation of PPAR gamma.
Cimen, I; Astarci, E; Banerjee, Sreeparna (Wiley, 2011-09-01)
15-Lipoxygenase-1 (15-LOX-1) is an enzyme of the inflammatory eicosanoid pathway whose expression is known to be lost in colorectal cancer (CRC). We have previously shown that reintroduction of the gene in CRC cell lines slows proliferation and induces apoptosis (Cimen et al. [2009] Cancer Sci 100: 2283-2291). We have hypothesized that 15-LOX-1 may be anti-tumorigenic by the inhibition of the antiapoptotic inflammatory transcription factor nuclear factor kappa B. We show here that ectopic expression of 15-L...
Citation Formats
N. Ozek Simsek, Y. Sara, R. Onur, and F. Severcan, “Low dose simvastatin induces compositional, structural and dynamic changes in rat skeletal extensor digitorum longus muscle tissue,” Bioscience Reports, pp. 41–50, 2009, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/50944.