Effect of 2,6-di-O-methyl-α-cyclodextrin on hemolysis and morphological change in rabbit's red blood cells

The effects of 2,6-di-O-methyl-α-cyclodextrin (DM-α-CyD) on hemolysis and morphological changes in rabbit's red blood cells (RBC) were examined, compared with those of α-cyclodextrin (CyD) and 2-hydoxypropyl-α-cyclodextrin (HP-α-CyD). The hemolytic activity of α-CyDs increased in the order of HP-α-CyD < α-CyD < DM-α-CyD. The three α-CyDs induced morphological changes of RBC from discocyte to stomatocyte. At the same concentration (3 mM) of α-CyDs, DM-α-CyD and α-CyD released phospholipids, rather than cholesterol, and DM-α-CyD markedly released proteins from RBC membranes, compared to α-CyD and HP-α-CyD. The treatment of RBC with DM-α-CyD lowered the extent of a fluorescent sphingomyelin analogue from lipid rafts of RBC membranes in a concentration-dependent manner. These results suggest that DM-α-CyD has higher hemolytic and morphological change activity than α-CyD and HP-α-CyD through more extraction of phospholipids including sphingomyelin and proteins, not cholesterol, from RBC membranes than α-CyD and HP-α-CyD.