Structural and functional effects of non-steroidal anti-inflammatory drugs rofecoxib and valdecoxib on DSPC model membranes

Rachkauska, Richardas
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 RFX and VLX were withdrawn from the market after clinical trials indicated that use of these drugs enhanced the risk of heart attack and stroke.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.


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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...
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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 simva...
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Biotransformation of the Fluorinated Nonsteroidal Anti-Inflammatory Pharmaceutical Flurbiprofen in Activated Sludge Results in Accumulation of a Recalcitrant Fluorinated Aromatic Metabolite
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Flurbiprofen is a fluorinated, nonsteroidal, anti-inflammatory pharmaceutical with potential application in a wide range of maladies. Currently, there is no information regarding its environmental fate. To address this, flurbiprofen is spiked at 500 and 50 ppm into activated sewage sludge taken from the municipal treatment plant of Ankara, Turkey. Flurbiprofen is partially degraded after 80 days, with removal proportion varying from 33% to 48%. Isolation of organisms able to use flurbiprofen as a sole carbo...
Citation Formats
R. Rachkauska, “Structural and functional effects of non-steroidal anti-inflammatory drugs rofecoxib and valdecoxib on DSPC model membranes,” M.S. - Master of Science, Middle East Technical University, 2014.