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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Main Authors: Cleide Oliveira, Mayara Vioto Valois, Tatiana Fontes Ottaiano, Antonio Miranda, Daiane Hansen, Misako Uemura Sampaio, Maria Luiza Vilela Oliva, Francisco Humberto de Abreu Maffei
Format: Article
Language:English
Published: Nature Portfolio 2021-06-01
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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