Effect of 2,6-di-O-methyl-alpha-cyclodextrin on hemolysis and morphological change in rabbit's red blood cells.
The effects of 2,6-di-O-methyl-alpha-cyclodextrin (DM-alpha-CyD) on hemolysis and morphological changes in rabbit's red blood cells (RBC) were examined, compared with those of alpha-cyclodextrin (CyD) and 2-hydoxypropyl-alpha-cyclodextrin (HP-alpha-CyD). The hemolytic activity of alpha-CyDs increased in the order of HP-alpha-CyD<alpha-CyD<DM-alpha-CyD. The three alpha-CyDs induced morphological changes of RBC from discocyte to stomatocyte. At the same concentration (3mM) of alpha-CyDs, DM-alpha-CyD and alpha-CyD released phospholipids, rather than cholesterol, and DM-alpha-CyD markedly released proteins from RBC membranes, compared to alpha-CyD and HP-alpha-CyD. The treatment of RBC with DM-alpha-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-alpha-CyD has higher hemolytic and morphological change activity than alpha-CyD and HP-alpha-CyD through more extraction of phospholipids including sphingomyelin and proteins, not cholesterol, from RBC membranes than alpha-CyD and HP-alpha-CyD.
Motoyama
Keiichi
K
Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
Arima
Hidetoshi
H
Toyodome
Hiroshi
H
Irie
Tetsumi
T
Hirayama
Fumitoshi
F
Uekama
Kaneto
K
D000818:Animals; D002784:Cholesterol / Q000032:analysis; D004912:Erythrocytes / Q000187:drug effects* / Q000473:pathology; D006461:Hemolysis / Q000187:drug effects*; D008297:Male; D021962:Membrane Microdomains / Q000737:chemistry; D011817:Rabbits; D013109:Sphingomyelins / Q000032:analysis; D047391:alpha-Cyclodextrins / Q000494:pharmacology*
D013109:Sphingomyelins; D047391:alpha-Cyclodextrins; C479660:dimethyl-alpha-cyclodextrin; D002784:Cholesterol