| Texto completo | |
| Autor(es): |
Nogueira, Ruben Siedlarczyk
;
Salu, Bruno Ramos
;
Nardelli, Vinicius Goulart
;
Bonturi, Camila Ramalho
;
Pereira, Marina Rodrigues
;
Maffei, Francisco Humberto de Abreu
;
Cilli, Eduardo Maffud
;
Oliva, Maria Luiza Vilela
Número total de Autores: 8
|
| Tipo de documento: | Artigo Científico |
| Fonte: | THROMBOSIS JOURNAL; v. 21, n. 1, p. 10-pg., 2023-01-02. |
| Resumo | |
Background: (p-BthTX-I)(2) K, a dimeric analog peptide derived from the C-terminal region of phospholipase A2-like bothropstoxin-I (p-BthTX-I), is resistant to plasma proteolysis and inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains with weak cytotoxic effects. Complications of SARS-CoV-2 infection include vascular problems and increased risk of thrombosis; therefore, studies to identify new drugs for treating SARS-CoV-2 infections that also inhibit thrombosis and minimize the risk of bleeding are required.Objectives: To determine whether (p-BthTX-I)(2) K affects the hemostatic system.Methods: Platelet aggregation was induced by collagen, arachidonic acid, and adenosine diphosphate (ADP) in the Chronolog Lumi-aggregometer. The coagulation activity was evaluated by determining activated partial thromboplastin clotting time (aPTT) and prothrombin time (PT) with (p-BthTX-I)(2) K (5.0-434.5 mu g) or 0.9% NaCl. Arterial thrombosis was induced with a 540 nm laser and 3.5-20 mg kg(- 1) Rose Bengal in the carotid artery of male C57BL/6J mice using (p-BthTX-I)(2) K. Bleeding time was determined in mouse tails immersed in saline at 37 & DEG;C after (p-BthTX-I)(2) K (4.0 mg/kg and 8.0 mg/kg) or saline administration.Results: (p-BthTX-I)(2) K prolonged the aPTT and PT by blocking kallikrein and FXa-like activities. Moreover, (p-BthTX-I)(2) K inhibited ADP-, collagen-, and arachidonic acid-induced platelet aggregation in a dose-dependent manner. Further, low concentrations of (p-BthTX-I)(2) K extended the time to artery occlusion by the formed thrombus. However, (p-BthTX-I)(2) K did not prolong the bleeding time in the mouse model of arterial thrombosis.Conclusion: These results demonstrate the antithrombotic activity of the peptide (p-BthTX-I)(2) K possibly by kallikrein inhibition, suggesting its strong biotechnological potential. (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 |
| Processo FAPESP: | 20/05761-3 - Estudo da ação de peptídeos sintéticos como antivirais contra o SARS-CoV-2 (COVID-19) e avaliação combinada com anti-inflamatórios comerciais |
| Beneficiário: | Eduardo Maffud Cilli |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 19/22243-9 - 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: | Camila Ramalho Bonturi |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 20/01512-9 - Mecanismo de ação de peptídeos miméticos derivados de Enterolobium contortisiliquum sobre a sinalização e função de plaquetas |
| Beneficiário: | Ruben Siedlarczyk Nogueira |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado Direto |