In vivo antithrombotic effect of triflavin, an Arg-Gly-Asp containing peptide on platelet plug formation in mesenteric microvessels of mice.
Triflavin, an Arg-Gly-Asp-containing snake venom peptide, inhibits platelet aggregation through the blockade of fibrinogen binding to the activated platelets. In this study, platelet thrombus formation was induced by irradiation of the mesenteric venules with filtered light in mice pretreated intravenously with fluorescein sodium. Electron microscopy reveals moderately damaged endothelial cells, as well as aggregates consisting almost exclusively of platelets with pseudopod formation, and degranulated appearance. Triflavin (10-20 micrograms/g) significantly prolonged the lag period of inducing platelet plug formation in mesenteric venules when it was intravenously infused. Triflavin (20 micrograms/g) prolonged the occlusion time about 2-fold (from control 112 +/- 23 to 240 +/- 47 s). Furthermore, PGE1 briefly prolonged the occlusion time about 1.5-fold (from 105 +/- 21 to 168 +/- 20 s) when it was given by continuous infusion (40 micrograms/kg/min). On the other hand, triflavin was also effective in reducing the mortality of ADP-induced acute pulmonary thromboembolism in mice when administered intravenously at dose of 2-4 micrograms/g. Heparin (1.5 U/g) and indomethacin (200 micrograms/g) had no significant effect in prolonging the occlusion time or in reducing ADP-induced pulmonary embolism in mice. Therefore, triflavin is an effective antithrombotic agent in preventing the thromboembolism in these two in vivo models.
Sheu
J R
JR
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei.
Chao
S H
SH
Yen
M H
MH
Huang
T F
TF
D000208:Acute Disease; D000244:Adenosine Diphosphate / Q000633:toxicity; D000527:Alprostadil / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004730:Endothelium, Vascular / Q000293:injuries / Q000473:pathology; D019793:Fluorescein; D005452:Fluoresceins / Q000528:radiation effects / Q000633:toxicity; D006493:Heparin / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008643:Mesentery / Q000098:blood supply*; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D009842:Oligopeptides; D010455:Peptides / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D011655:Pulmonary Embolism / Q000139:chemically induced / Q000517:prevention & control; D013927:Thrombosis / Q000517:prevention & control*; D014699:Venules
D005452:Fluoresceins; D009842:Oligopeptides; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; C070025:triflavin; D000244:Adenosine Diphosphate; C047981:arginyl-glycyl-aspartic acid; D006493:Heparin; D000527:Alprostadil; D019793:Fluorescein; D007213:Indomethacin