In this study, the effects of anesthetic drug sevoflurane on membrane fluidity have been compared with isoflurane. To get complete picture, three representative membrane systems (pure DPPC, POPC/Chol and a 5-lipids mixture that mimics brain endothelial cell membrane) and red blood cells were chosen. Lipid membrane systems were labeled with dipyrene-PC fluorescent probe, whose excimer/monomer (E/M) fluorescence peak ratio showed an immediate increase after adding the drugs, indicating a sharp increase of membrane fluidity. We studied clinical concentrations of 0.5mM sevoflurane and 1mM isoflurane. The fluidity increase at these concentrations on DPPC lipid bilayer are comparable, and both drugs are quite effective to loosen up the highly ordered lipid domains of saturated lipids. The supra-clinical concentrations of these drugs, 2mM sevoflurane and 5mM isoflurane, have also been examined. The E/M ratio increases for POPC/Chol and 5-lipids mixture were similar, but the magnitude of increases were reduced to almost half of DPPC. Furthermore, washed human red blood cells were labeled with TMA-DPH fluorescent probe and fluorescence anisotropy measurements were carried out. At clinical concentrations, the decreases of anisotropy were comparable for these two drugs, and the effects are more than that of 174mM ethanol, which is ten times the legal alcohol limit level in human blood. All these findings depict that sevoflurane and isoflurane at clinical concentrations have similar effects on a wide range of membrane systems, and both significantly and rapidly increase membrane fluidity. |