The recombinant plant Bauhinia bauhinioides elastase inhibitor reduces rat thrombus without alterations in hemostatic parameters
Abstract The anti-inflammatory effects of the plant protease inhibitor BbCI (Bauhinia bauhinioides cruzipain inhibitor), which blocks elastase, cathepsin G, and L, and proteinase 3 has been demonstrated. Here, we investigated the recombinant rBbCI-His(6) (containing a histidine tail) in an experimen...
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Nature Portfolio
2021-06-01
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Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-021-92745-4 |
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author | Cleide Oliveira Mayara Vioto Valois Tatiana Fontes Ottaiano Antonio Miranda Daiane Hansen Misako Uemura Sampaio Maria Luiza Vilela Oliva Francisco Humberto de Abreu Maffei |
author_facet | Cleide Oliveira Mayara Vioto Valois Tatiana Fontes Ottaiano Antonio Miranda Daiane Hansen Misako Uemura Sampaio Maria Luiza Vilela Oliva Francisco Humberto de Abreu Maffei |
author_sort | Cleide Oliveira |
collection | DOAJ |
description | Abstract The anti-inflammatory effects of the plant protease inhibitor BbCI (Bauhinia bauhinioides cruzipain inhibitor), which blocks elastase, cathepsin G, and L, and proteinase 3 has been demonstrated. Here, we investigated the recombinant rBbCI-His(6) (containing a histidine tail) in an experimental venous thrombosis model of vena cava (VC) ligature in rats, comparing to heparin. We evaluate the effects of the inhibitors (native or recombinant) or heparin on the activated partial thromboplastin time (aPTT) and prothrombin time (PT) in human and rat plasmas. The rats undergoing treatment received a saline solution or increasing concentrations of rBbCI-His(6), heparin, or a mixture of both. After 4 h of ligature VC, thrombus, if present was removed and weighed. aPTT, PT, and cytokines were measured in blood collected by cardiac puncture. aPTT, PT, and bleeding time (BT) were also measured at the time of VC (vena cava) ligature. rBbCI-His(6) (0.45 or 1.40 mg/kg) does not alter aPTT, PT or BT. No differences in coagulation parameters were detected in rBbCI-His(6) treated rats at the time of VC ligature or when the thrombus was removed. There was a significant decrease in the weight of thrombus in the animals of the groups treated with the rBbCI-His(6) (1.40 mg/kg), with the rBbCI-His(6) mixture (1.40 mg/kg) + heparin (50 IU/kg) and heparin (100 IU/kg) in relation to control group (saline). The growth-related oncogene/keratinocyte chemoattractant (GRO/KC) serum levels in rats treated with rBbCI-His(6) (1.40 mg/kg) or heparin (200 IU/kg) were reduced. In the experimental model used, rBbCI-His(6) alone had an antithrombotic effect, not altering blood clotting or bleeding time. |
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spelling | doaj.art-5077b7d1b41043ba8742f50087c68a8f2022-12-21T23:00:18ZengNature PortfolioScientific Reports2045-23222021-06-0111111210.1038/s41598-021-92745-4The recombinant plant Bauhinia bauhinioides elastase inhibitor reduces rat thrombus without alterations in hemostatic parametersCleide Oliveira0Mayara Vioto Valois1Tatiana Fontes Ottaiano2Antonio Miranda3Daiane Hansen4Misako Uemura Sampaio5Maria Luiza Vilela Oliva6Francisco Humberto de Abreu Maffei7Departamento de Bioquímica, Universidade Federal de São PauloDepartamento de Bioquímica, Universidade Federal de São PauloDepartamento de Bioquímica, Universidade Federal de São PauloDepartamento de Biofísica, Universidade Federal de São PauloDepartamento de Bioquímica, Universidade Federal de São PauloDepartamento de Bioquímica, Universidade Federal de São PauloDepartamento de Bioquímica, Universidade Federal de São PauloDepartamento de Cirurgia e Ortopedia, Universidade Estadual PaulistaAbstract The anti-inflammatory effects of the plant protease inhibitor BbCI (Bauhinia bauhinioides cruzipain inhibitor), which blocks elastase, cathepsin G, and L, and proteinase 3 has been demonstrated. Here, we investigated the recombinant rBbCI-His(6) (containing a histidine tail) in an experimental venous thrombosis model of vena cava (VC) ligature in rats, comparing to heparin. We evaluate the effects of the inhibitors (native or recombinant) or heparin on the activated partial thromboplastin time (aPTT) and prothrombin time (PT) in human and rat plasmas. The rats undergoing treatment received a saline solution or increasing concentrations of rBbCI-His(6), heparin, or a mixture of both. After 4 h of ligature VC, thrombus, if present was removed and weighed. aPTT, PT, and cytokines were measured in blood collected by cardiac puncture. aPTT, PT, and bleeding time (BT) were also measured at the time of VC (vena cava) ligature. rBbCI-His(6) (0.45 or 1.40 mg/kg) does not alter aPTT, PT or BT. No differences in coagulation parameters were detected in rBbCI-His(6) treated rats at the time of VC ligature or when the thrombus was removed. There was a significant decrease in the weight of thrombus in the animals of the groups treated with the rBbCI-His(6) (1.40 mg/kg), with the rBbCI-His(6) mixture (1.40 mg/kg) + heparin (50 IU/kg) and heparin (100 IU/kg) in relation to control group (saline). The growth-related oncogene/keratinocyte chemoattractant (GRO/KC) serum levels in rats treated with rBbCI-His(6) (1.40 mg/kg) or heparin (200 IU/kg) were reduced. In the experimental model used, rBbCI-His(6) alone had an antithrombotic effect, not altering blood clotting or bleeding time.https://doi.org/10.1038/s41598-021-92745-4 |
spellingShingle | Cleide Oliveira Mayara Vioto Valois Tatiana Fontes Ottaiano Antonio Miranda Daiane Hansen Misako Uemura Sampaio Maria Luiza Vilela Oliva Francisco Humberto de Abreu Maffei The recombinant plant Bauhinia bauhinioides elastase inhibitor reduces rat thrombus without alterations in hemostatic parameters Scientific Reports |
title | The recombinant plant Bauhinia bauhinioides elastase inhibitor reduces rat thrombus without alterations in hemostatic parameters |
title_full | The recombinant plant Bauhinia bauhinioides elastase inhibitor reduces rat thrombus without alterations in hemostatic parameters |
title_fullStr | The recombinant plant Bauhinia bauhinioides elastase inhibitor reduces rat thrombus without alterations in hemostatic parameters |
title_full_unstemmed | The recombinant plant Bauhinia bauhinioides elastase inhibitor reduces rat thrombus without alterations in hemostatic parameters |
title_short | The recombinant plant Bauhinia bauhinioides elastase inhibitor reduces rat thrombus without alterations in hemostatic parameters |
title_sort | recombinant plant bauhinia bauhinioides elastase inhibitor reduces rat thrombus without alterations in hemostatic parameters |
url | https://doi.org/10.1038/s41598-021-92745-4 |
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