Effects of the antiplatelet agent TA-993 and its metabolite MB3 on the hemorheological properties of rat and human erythrocytes.
In the present study, we investigated the effects of the antiplatelet agent TA-993 and its metabolite MB3 on the hemorheological properties of rat and human erythrocytes in comparison with ticlopidine and aspirin. TA-993 and MB3 concentration-dependently lowered the viscosity of rat erythrocyte suspensions. TA-993 and MB3 inhibited both the hypotonic hemolysis of human erythrocytes and the mechanical hemolysis of rat erythrocytes induced by turbulent flow. Treatment of rats with TA-993 (10 mg/kg/day po) for 10 days significantly increased blood filterability, but ticlopidine and aspirin did not show this effect. TA-993 and MB3 enhanced the interaction of 1-anilino-8-naphthalene sulfonate (ANS), a hydrophobic probe, with human erythrocyte ghosts and reduced the fluorescence polarization in 1,6-diphenyl 1,3,5-hexatriene (DPH, a fluidity probe)-labeled human erythrocyte ghosts. TA-993 and MB3 induced aggregation of liposome suspensions prepared from acidic phospholipids. These findings suggest that TA-993 and MB3 may affect the erythrocyte membrane by interacting with acidic phospholipids and thus improve the hemorheological properties.
Katoh
M
M
Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd., 2-2-50, Kawagishi, Toda-shi, Saitama, 335-8505, Japan. katoh-m@tanabe.co.jp
Karasawa
T
T
Doi
H
H
Odawara
A
A
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001809:Blood Viscosity / Q000187:drug effects; D004110:Diltiazem / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects; D018056:Hemorheology / Q000187:drug effects*; D006801:Humans; D010743:Phospholipids / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D013988:Ticlopidine / Q000494:pharmacology
D010743:Phospholipids; D010975:Platelet Aggregation Inhibitors; C446199:metabolite MB3; C097363:TA 993; D004110:Diltiazem; D013988:Ticlopidine; D001241:Aspirin