Inhibition of platelet aggregation by polyaspartoyl L-arginine and its mechanism
Abstract
AIM:
To observe the oral anti-platelet efficacy and the potential action mechanism of polyaspartoyl L-arginine (PDR), a new L-arginine rich compound.
METHODS:
Platelet aggregation was conducted by Born's method; bleeding time was determined using tail's bleeding time in mice; platelet adhesion was carried out with glass bottle method; nitric oxide (NO) was tested with Griess's method; and cAMP, thromboxane B(2) (TXB(2)) and 6-keto-PGF(1 alpha ) were assessed with commercial kits.
RESULTS:
The inhibition by PDR (15-60 mg/kg i.g. or 10 mg/kg i.v.) of platelet aggregation induced by adenosine diphosphate (ADP), collagen or thrombin at 1 h after oral administration or at 20 min after i.v. injection for rats (P<0.01), and its (15 mg/kg, i.g.) inhibition of ADP-induced platelet aggregation for rabbits during 6 h after administration were observed. PDR (15-60 mg/kg) prolonged the bleeding time of mice (P<0.05) and (30 mg/kg) increased NO concentration in plasma. On the other hand PDR did not change the contents of cAMP in platelet and TXB2 or 6-keto-PGF(1 alpha) in plasma.
CONCLUSION:
PDR is a novel, oral effective platelet aggregation inhibitor and its action mechanism possibly related to increasing NO generation.
Keywords:
To observe the oral anti-platelet efficacy and the potential action mechanism of polyaspartoyl L-arginine (PDR), a new L-arginine rich compound.
METHODS:
Platelet aggregation was conducted by Born's method; bleeding time was determined using tail's bleeding time in mice; platelet adhesion was carried out with glass bottle method; nitric oxide (NO) was tested with Griess's method; and cAMP, thromboxane B(2) (TXB(2)) and 6-keto-PGF(1 alpha ) were assessed with commercial kits.
RESULTS:
The inhibition by PDR (15-60 mg/kg i.g. or 10 mg/kg i.v.) of platelet aggregation induced by adenosine diphosphate (ADP), collagen or thrombin at 1 h after oral administration or at 20 min after i.v. injection for rats (P<0.01), and its (15 mg/kg, i.g.) inhibition of ADP-induced platelet aggregation for rabbits during 6 h after administration were observed. PDR (15-60 mg/kg) prolonged the bleeding time of mice (P<0.05) and (30 mg/kg) increased NO concentration in plasma. On the other hand PDR did not change the contents of cAMP in platelet and TXB2 or 6-keto-PGF(1 alpha) in plasma.
CONCLUSION:
PDR is a novel, oral effective platelet aggregation inhibitor and its action mechanism possibly related to increasing NO generation.