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.