Determination of Simvastatin Induced Variations in Sciatic Nerve by ATR-FTIR Spectroscopy

Abstract

Simvastatin, a lipophilic statin derived drug, is commonly used drug for treating lipid and cardiovascular disorders. It is well known that the long term usage of this drug leads to peripheral neuropathy, mononeuropathy and memory problems. Moreover a possible treating agent in central nervous system disease like Alzheimer has been reported. The results that were obtained from simvastatin and nervous system are clinically unclear and controversial. Therefore the current study was aimed to clarify the possible effects of simvastatin on the content, composition, dynamics and conformation of macromolecules in rat sciatic nerve using ATR-FTIR Spectroscopy. Experimental male adult rats were divided two groups as control (n=10) and simvastatin-treated group (n=10). 50 mg simvastatin/ kg was given to treated group by oral gavage for 1 month. In the FTIR spectra, the shift in peak positions, the change in bandwidths and the intensity/area values of the bands were determined and compared in between control and treated groups. The results revealed that there is a significant decrease in amount of unsaturated lipid in simvastatin treated sciatic nerve, which indicates an increase in lipid peroxidation. Moreover, with simvastatin treatment a reduction in the saturated lipid, protein, glycogen and nucleic acid content was found showing degradation or decrease in the synthesis of these molecules. Protein secondary structure was found to be changed as a decrease in α-helix and β-sheet content and an increase aggregated β-sheet and random coil content in treated samples implying protein denaturation. The outcomes of this study show that high dose simvastatin application leads to structural and molecular variations in sciatic nerve by affecting its macromolecular composition.Keywords: sciatic nerve, simvastatin, statin, ATR-FTIR spectroscopy, protein secondary structure.