Cyclooxygenase-2 Inhibition by Etoricoxib Modulates Plasma Membrane Fluidity in Rat Colon

Abstract

The present study was designed to investigate the effects of a selective cycloogenase-2 (COX-2) inhibitor, etoricoxib, on the membrane-specific enzymes, lipid composition, and changes in fluidity parameters of rat colonic plasma membrane. Two doses of the drug were used, one within its therapeutic anti-inflammatory range as based on the ED50 value in rats (Eto-1), while the other at 10 times higher dose relating to the toxicity studies (Eto-2), which have not been reported so far. The activity of the membrane alkaline phosphatase was found to be increased after treatment with both the doses of etoricoxib as compared to the control. The total lipid and the cholesterol content showed a decrease while an increase in ganglioside sialic acid content was noted. Phospholipid content and the cholesterol-phospholipid molar ratio showed no change in either of the treatment groups. Fluorescence polarization studies with diphenylhexatriene showed that membrane fluidity was least altered in the isolated brush border membrane from colon or in the liposomes prepared from the membrane lipid extracts. Also, the translational diffusion studied with pyrene showed that the fluidity parameter was decreased as measured by the excimer formation. It is concluded that etoricoxib, a new generation COX-2 inhibitor (called the coxibs), appeared to be a safe nonsteroidal anti-inflammatory drug (NSAID) in the colonic membranes.