Investigation of drug-related changes on bone tissues of rat animal models in healthy and disease states

Garip, Şebnem
Disease- and drug-related bone disorders are rapidly increasing in the population. The drugs which are used for the treatment of neurodegenerative diseases and metabolic derangements, may have negative or positive effects on bone tissues. In the first study, the possible side-effects of Carbamazepine and epileptic seizures on bone structure and composition were investigated by FTIR and synchrotron-FTIR microspectroscopy, AFM and micro- and nano-hardness analysis. The effects on the blood parameters, bone turnover and vitamin D metabolism were also investigated by ELISA and western blot analysis. The current study provides the first report on differentiation of the effects of both epileptic seizures and AED therapy on bones. Besides Carbamazepine treatment, seizures also caused a decrease in the strength of bone. The biochemical data showed that both the epileptic and drug-treated groups decreased vitamin D levels by increasing the vitamin D catabolism enzyme; 25-hydroxyvitamin D-24-hydroxylase. In the second study, the possible pleiotropic (positive) effects of cholesterol lowering drug; Simvastatin on bones were investigated by ATR-FTIR spectroscopy. The current study provides the first report on dose-dependent effects of simvastatin on protein structure and lipid conformation of bones. ATR-FTIR studies showed that although both high and low dose simvastatin strengthen bones, low dose simvastatin treatment is much more effective in increasing bone strength. Neural network analysis revealed an increased antiparallel and aggregated beta sheet and random coil in the protein secondary structure of high dose group implying a protein denaturation. Moreover, high dose may induce lipid peroxidation which limit the pleiotropic effects of high dose treatment on bones. This study clearly demonstrated that using low dose simvastatin is safer and more effective for bone health than high dose simvastatin treatment.


Epileptic seizure-induced structural and functional changes in rat femur and tibia bone tissues: a Fourier transform infrared imaging study
Garip, Sebnem; ŞAHİN, DENİZ; Severcan, Feride (2013-11-01)
The disease- and drug- related bone disorders are rapidly increasing in the population. It is previously reported that anti-epileptic drugs (AEDs) may cause osteopenia, osteoporosis, and fractures in epilepsy patients. However, it cannot be determined whether the bone disorders in epileptic patients are due to AED therapy and/or to epilepsy and epileptic seizures. There is no study in the literature which investigates the sole effects of epilepsy and epileptic seizures on bone tissues. The current study pro...
Evin, Emre; Adalı, Orhan; Department of Biology (2021-8)
Multiple sclerosis (MS) is a complicated, recurrent, and often progressive inflammatory demyelinating autoimmune disease of the central nervous system, yet etiopathogenesis remains unsolved. MS frequency increases with increasing latitude, leading to a hypothesis that MS is inversely correlated with the duration and intensity of sunlight and vitamin D concentrations. In this study, the relationships between vitamin D supplementation, MS, VDR, and vitamin D metabolizing CYP enzymes, including CYP2R1, CYP27A1...
Investigation of diabetes-induced effect on apex of rat heart myocardium by using cluster analysis and neural network approach: An FTIR study
Toyran, Neslihan; Severcan, Feride; Severcan, Mete; Turan, Belma (Hindawi Limited, 2007)
Diabetes mellitus (DM) is a progressive chronic disorder, which affects people belonging to all age groups of the population. This disease is accompanied by a greatly increased risk of cardiovascular death. In the present study, the effects of streptozotocin (STZ)-induced type 1 diabetes on apex myocardium of the rat heart have been investigated using Fourier Transform Infrared (FTIR) spectra. The cluster analysis has been applied to FTIR spectra to differentiate the diabetic samples from the normal control...
Association between gamma aminobutyric acid (GABA) type B receptors gene polymorphisms and idiopathic generalized epilepsy
Eroğlu, Ezgi; Adalı, Orhan; Demirdöğen, Birsen Can; Department of Biology (2011)
Epilepsy is neurological disorder affecting 0.5 to 1% of the population all around the world. It is characterized by the seizures, which are the sudden alterations of behavior due to a temporary change in electrical functioning of the brain. Idiopathic generalized epilepsy (IGE) accounts for one-fifth of all the other epilepsy types, and several gene mutations were identified as the causes of IGE. In general, voltage-gated and ligand-gated ion channel mutations are linked with seizure formation. Gamma amino...
Investigation of on skin surface response due to acoustic radiation from stenosed blood vessels
Salman, Huseyin E.; Yazıcıoğlu, Yiğit (2015-11-02)
Arterial stenosis is a form of cardiovascular disease which leads to highest rate of fatalities worldwide. When stenosis is present in coronary arteries, it leads to heart attack and often sudden death. Arterial disease is usually not confined to critical organs such as the heart and the brain but observed throughout the peripheral cardiovascular system. When an artery has a diameter reduction, acoustic radiation originating from this constriction propagates through soft tissues and reaches to skin surface....
Citation Formats
Ş. Garip, “Investigation of drug-related changes on bone tissues of rat animal models in healthy and disease states,” Ph.D. - Doctoral Program, Middle East Technical University, 2012.