| Full text | |
| Author(s): |
Medina, A. F.
;
Salu, B. R.
;
de Brito, M. V.
;
Bonturi, C. R.
;
Meneghetti, M. C. Z.
;
Maffei, F. H. A.
;
Oliva, M. L. V.
Total Authors: 7
|
| Document type: | Journal article |
| Source: | Process Biochemistry; v. 122, p. 12-pg., 2022-08-22. |
| Abstract | |
Coagulation contact pathway inhibitors have aroused interest in the treatment and prevention of thrombosis due to their lower hemorrhagic effects. We investigate the recombinant kallikrein inhibitor (rBbKIm) containing the RGD/RGE motif and its related peptides in arterial thrombosis models. rBbKIm prolonged activated partial thromboplastin time by 3.5 (8.6 mu M) and 4.1 times (17.2 mu M), and extended the arterial occlusion time in a dose -dependent manner: 2.0 mg/kg (48.83 +/- 15.87 min), 4.0 mg/kg (73.06 +/- 21.38 min) and 8.0 mg/kg (94.13 +/- 11.25 min) compared with control (0.15 M NaCl, 29.70 +/- 7.14 min). Similar results were obtained with the RGD-peptide, 2.5 mg/kg (62.85 +/- 18.53 min) and 5.0 mg/kg (89.50 +/- 8.63 min). Thrombus sizes were decreased in the rBbKIm, RGD-peptide, and fondaparinux (0.7 mg/kg) treated groups, due to reduced adhesion of platelet to the endothelium. ADP-induced platelet aggregation ex vivo was inhibited by both rBbKIm (4.0 mg/ kg, 75 %) and the RGD-peptide (5.0 mg/kg, 56 %), and they did not modify the bleeding time in contrast to fondaparinux. rBbKIm and RGD-related-peptide delayed the artery occlusion and reduced the thrombus size without any modification of the bleeding time, thereby impairing the aggregation and/or adhesion of platelets, making them useful for thrombosis therapy. (AU) | |
| FAPESP's process: | 17/06630-7 - Fragments derived from the structure of protease inhibitors with selectivity for inhibition of mammalian and microorganism enzymes and its role as an anti-inflammatory, antimicrobial, antithrombotic and anti- tumor agent: mechanism of action |
| Grantee: | Maria Luiza Vilela Oliva |
| Support Opportunities: | Research Projects - Thematic Grants |