title: Structural effects of simvastatin on liver rat [corrected] tissue: Fourier transform infrared and Raman microspectroscopic studies.
abstract: Simvastatin is one of the most frequently prescribed statins because of its efficacy in the treatment of hypercholesterolemia, reducing cardiovascular risk and related mortality. Determination of its side effects on different tissues is mandatory to improve safe use of this drug. In the present study, the effects of simvastatin on molecular composition and structure of healthy rat livers were investigated by Fourier transform infrared and Raman imaging. Simvastatin-treated groups received 50 mg/kg/day simvastatin for 30 days. The ratio of the area and/or intensity of the bands assigned to lipids, proteins, and nucleic acids were calculated to get information about the drug-induced changes in tissues. Loss of unsaturation, accumulation of end products of lipid peroxidation, and alterations in lipid-to-protein ratio were observed in the treated group. Protein secondary structure studies revealed significant decrease in α-helix and increase in random coil, while native β-sheet decreases and aggregated β-sheet increases in treated group implying simvastatin-induced protein denaturation. Moreover, groups were successfully discriminated using principal component analysis. Consequently, high-dose simvastatin treatment induces hepatic lipid peroxidation and changes in molecular content and protein secondary structure, implying the risk of liver disorders in drug therapy.
authors.affiliation: Istanbul Kemerburgaz University, Department of Medical Biochemistry, Faculty of Medicine, Mahmutbey Dilmenler Caddesi, No: 26, Istanbul 34217, Turkey.
authors.forename: Sebnem
authors.initials: S
authors.lastname: Garip
authors.affiliation: Hacettepe University, Department of Physics Engineering, Faculty of Engineering, Beytepe Campus, Ankara 06800, Turkey.
authors.forename: Sevgi Haman
authors.initials: SH
authors.lastname: Bayari
authors.affiliation: Middle East Technical University, Department of Electrical and Electronics Engineering, Faculty of Engineering, Dumlupinar Bulvari, No: 1, Ankara 06800, Turkey.
authors.forename: Mete
authors.initials: M
authors.lastname: Severcan
authors.affiliation: Middle East Technical University, Department of Biological Sciences, Faculty of Arts and Sciences, Dumlupinar Bulvari, No: 1, Ankara 06800, Turkey.
authors.forename: Sherif
authors.initials: S
authors.lastname: Abbas
authors.affiliation: University at Albany, Department of Chemistry, State University of New York, Albany, New York 12222, United States.
authors.forename: Igor K
authors.initials: IK
authors.lastname: Lednev
authors.affiliation: University at Albany, Department of Chemistry, State University of New York, Albany, New York 12222, United States.
authors.forename: Feride
authors.initials: F
authors.lastname: Severcan
mesh_terms: D000465:Algorithms; D000818:Animals; D007091:Image Processing, Computer-Assisted; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D016571:Neural Networks, Computer; D025341:Principal Component Analysis; D051381:Rats; D019821:Simvastatin / Q000009:adverse effects*; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods*; D013059:Spectrum Analysis, Raman / Q000379:methods*
chemical_list: D019821:Simvastatin