Akademik Veri Yönetim Sistemi
Tezin Türü: Yüksek Lisans
Tezin Yürütüldüğü Kurum: Orta Doğu Teknik Üniversitesi, Fen Edebiyat Fakültesi, Biyolojik Bilimler Bölümü, Türkiye
Tezin Onay Tarihi: 2014
Öğrenci: RICHARDAS RACHKAUSKAS
Danışman: SREEPARNA BANERJEE
Özet:Celecoxib (CLX), rofecoxib (RFX) and valdecoxib (VLX) belong to a family of Non-steroidal anti-inflammatory drugs (NSAIDs), which are selective COX-2 inhibitors. While these drugs are established analgesics, they also have a number of pleiotropic effects such as cancer chemoprevention, occasionally in a COX-2 independent manner. RFX and VLX were withdrawn from the market after clinical trials indicated that use of these drugs enhanced the risk of heart attack and stroke. CLX is currently FDA approved for pain management in rheumatoid arthritis. As these drugs are highly hydrophobic in nature, studies are underway on how the drugs can alter membrane properties such as fluidity, phase transition temperature and others. It has been shown that these drugs can affect lipid membrane properties such as fluidity and order and induce phase separation. Using differential scanning calorimetry (DSC) and Fourier transform infrared (FT-IR) spectroscopy, the current study compares the effects of RFX and VLX on DSPC model membrane properties. Additionally, the effects of these drugs were compared with effects of CLX previously reported by our group. We have observed that VLX can alter the properties of DSPC model membranes in a manner very similar to CLX: it decreases the phase transition temperature (Tm) in a concentration-dependent manner and also has effects on the fluidity. FT-IR and DSC studies show that increasing drug concentration enhances some of these effects. Interestingly, RFX appears to have a different effect on membrane fluidity and no effect on Tm. The data show no difference in biophysical properties between the control DSPC membranes and RFX treated membranes at various concentrations. Given the fact that CLX and VLX have a common sulfonamide group while RFX lacks it and only has sulfone group, we suggest that the sulfonamide group may be responsible for specific interactions with the lipid bilayers altering the biophysical properties of model membranes. Additionally, some unique effects observed only with CLX are attributed to the presence of Fluorine functional group in the drug. The results provide us new insights into NSAID-lipid interactions which can help delineate further the effects of these drugs on cell membrane.