| Texto completo | |
| Autor(es): |
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.
Número total de Autores: 7
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Process Biochemistry; v. 122, p. 12-pg., 2022-08-22. |
| Resumo | |
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) | |
| Processo FAPESP: | 17/06630-7 - Fragmentos derivados de proteínas com seletividade para inibição de enzimas de mamíferos e micro-organismos e seu papel como agente anti-inflamatório, antimicrobiano, antitrombótico e antitumoral: mecanismo de ação |
| Beneficiário: | Maria Luiza Vilela Oliva |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |