The First Anti-Snakebite and Hepatoprotective Characterization of a Trypsin Kunitz-like Inhibitor (EcTI) from the Plant <i>Enterolobium contortisiliquum;</i> A Case of Two Soul Mates Meeting
Snake venom serine protease (SVSP) interferes with the regulation and control of important biological reactions in homeostasis and can be classified as an activator of the fibrinolytic system and platelet aggregation. Our group has recently isolated a new serine protease from <i>Crotalus duris...
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| Format: | Article |
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MDPI AG
2023-04-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/4/632 |
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| author | Caroline R. C. Costa Mariana N. Belchor Airam Roggero Laila L. Moraes Ricardo Samelo Isabelly Annunciato Camila R. Bonturi Maria L. V. Oliva Sergio F. Sousa Marcos A. de Oliveira Marcos H. Toyama |
| author_facet | Caroline R. C. Costa Mariana N. Belchor Airam Roggero Laila L. Moraes Ricardo Samelo Isabelly Annunciato Camila R. Bonturi Maria L. V. Oliva Sergio F. Sousa Marcos A. de Oliveira Marcos H. Toyama |
| author_sort | Caroline R. C. Costa |
| collection | DOAJ |
| description | Snake venom serine protease (SVSP) interferes with the regulation and control of important biological reactions in homeostasis and can be classified as an activator of the fibrinolytic system and platelet aggregation. Our group has recently isolated a new serine protease from <i>Crotalus durissus terrificus</i> total venom (Cdtsp-2). This protein exhibits edematogenic capacity and myotoxic activity. A Kunitz-like EcTI inhibitor protein with a molecular mass of 20 kDa was isolated from <i>Enterolobium contortisiliquum</i> and showed high trypsin inhibition. Thus, the objective of this work is to verify the possible inhibition of the pharmacological activities of Cdtsp-2 by the Kutinz-type inhibitor EcTI. To isolate Cdtsp-2 from total <i>C. d. terrificus</i> venom, we used three-step chromatographic HPLC. Using the mice paw edema model, we observed an edematogenic effect, myotoxicity and hepatotoxicity caused by Cdtsp-2. In vitro and in vivo experiments showed that the alterations in hemostasis caused by Cdtsp-2 are crucial for the development of marked hepatotoxicity and that EcTI significantly inhibits the enzymatic and pharmacological activities of Cdtsp-2. Kunitz-like inhibitor may be a viable alternative for the development of ancillary treatments against the biological activities of venoms. |
| first_indexed | 2024-03-11T04:38:33Z |
| format | Article |
| id | doaj.art-badf2beca4ff48c2bbd3bd0f3547816f |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-11T04:38:33Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-badf2beca4ff48c2bbd3bd0f3547816f2023-11-17T20:51:40ZengMDPI AGPharmaceuticals1424-82472023-04-0116463210.3390/ph16040632The First Anti-Snakebite and Hepatoprotective Characterization of a Trypsin Kunitz-like Inhibitor (EcTI) from the Plant <i>Enterolobium contortisiliquum;</i> A Case of Two Soul Mates MeetingCaroline R. C. Costa0Mariana N. Belchor1Airam Roggero2Laila L. Moraes3Ricardo Samelo4Isabelly Annunciato5Camila R. Bonturi6Maria L. V. Oliva7Sergio F. Sousa8Marcos A. de Oliveira9Marcos H. Toyama10Center of Natural and Human Sciences, Federal University of ABC (UFABC), Santo André 09210-580, SP, BrazilCenter of Natural and Human Sciences, Federal University of ABC (UFABC), Santo André 09210-580, SP, BrazilBiosciences Institute of Paulista Coast Campus (IB/CLP), University of São Paulo State (UNESP), São Vicente 11330-900, SP, BrazilBiosciences Institute of Paulista Coast Campus (IB/CLP), University of São Paulo State (UNESP), São Vicente 11330-900, SP, BrazilBiosciences Institute of Paulista Coast Campus (IB/CLP), University of São Paulo State (UNESP), São Vicente 11330-900, SP, BrazilBiosciences Institute of Paulista Coast Campus (IB/CLP), University of São Paulo State (UNESP), São Vicente 11330-900, SP, BrazilNational Institute of Pharmacology (INFAR), Federal University of São Paulo (UNIFESP), São Paulo 04044-020, SP, BrazilNational Institute of Pharmacology (INFAR), Federal University of São Paulo (UNIFESP), São Paulo 04044-020, SP, BrazilUnit of Applied Biomolecular Sciences (UCIBIO), REQUIMTE-BioSIM-Medicine Faculty, Porto University, 4050-345 Porto, PortugalCenter of Natural and Human Sciences, Federal University of ABC (UFABC), Santo André 09210-580, SP, BrazilCenter of Natural and Human Sciences, Federal University of ABC (UFABC), Santo André 09210-580, SP, BrazilSnake venom serine protease (SVSP) interferes with the regulation and control of important biological reactions in homeostasis and can be classified as an activator of the fibrinolytic system and platelet aggregation. Our group has recently isolated a new serine protease from <i>Crotalus durissus terrificus</i> total venom (Cdtsp-2). This protein exhibits edematogenic capacity and myotoxic activity. A Kunitz-like EcTI inhibitor protein with a molecular mass of 20 kDa was isolated from <i>Enterolobium contortisiliquum</i> and showed high trypsin inhibition. Thus, the objective of this work is to verify the possible inhibition of the pharmacological activities of Cdtsp-2 by the Kutinz-type inhibitor EcTI. To isolate Cdtsp-2 from total <i>C. d. terrificus</i> venom, we used three-step chromatographic HPLC. Using the mice paw edema model, we observed an edematogenic effect, myotoxicity and hepatotoxicity caused by Cdtsp-2. In vitro and in vivo experiments showed that the alterations in hemostasis caused by Cdtsp-2 are crucial for the development of marked hepatotoxicity and that EcTI significantly inhibits the enzymatic and pharmacological activities of Cdtsp-2. Kunitz-like inhibitor may be a viable alternative for the development of ancillary treatments against the biological activities of venoms.https://www.mdpi.com/1424-8247/16/4/632serine proteaseCdtsp-2Kunitz-type inhibitor<i>Crotalus durissus terrificus</i> |
| spellingShingle | Caroline R. C. Costa Mariana N. Belchor Airam Roggero Laila L. Moraes Ricardo Samelo Isabelly Annunciato Camila R. Bonturi Maria L. V. Oliva Sergio F. Sousa Marcos A. de Oliveira Marcos H. Toyama The First Anti-Snakebite and Hepatoprotective Characterization of a Trypsin Kunitz-like Inhibitor (EcTI) from the Plant <i>Enterolobium contortisiliquum;</i> A Case of Two Soul Mates Meeting Pharmaceuticals serine protease Cdtsp-2 Kunitz-type inhibitor <i>Crotalus durissus terrificus</i> |
| title | The First Anti-Snakebite and Hepatoprotective Characterization of a Trypsin Kunitz-like Inhibitor (EcTI) from the Plant <i>Enterolobium contortisiliquum;</i> A Case of Two Soul Mates Meeting |
| title_full | The First Anti-Snakebite and Hepatoprotective Characterization of a Trypsin Kunitz-like Inhibitor (EcTI) from the Plant <i>Enterolobium contortisiliquum;</i> A Case of Two Soul Mates Meeting |
| title_fullStr | The First Anti-Snakebite and Hepatoprotective Characterization of a Trypsin Kunitz-like Inhibitor (EcTI) from the Plant <i>Enterolobium contortisiliquum;</i> A Case of Two Soul Mates Meeting |
| title_full_unstemmed | The First Anti-Snakebite and Hepatoprotective Characterization of a Trypsin Kunitz-like Inhibitor (EcTI) from the Plant <i>Enterolobium contortisiliquum;</i> A Case of Two Soul Mates Meeting |
| title_short | The First Anti-Snakebite and Hepatoprotective Characterization of a Trypsin Kunitz-like Inhibitor (EcTI) from the Plant <i>Enterolobium contortisiliquum;</i> A Case of Two Soul Mates Meeting |
| title_sort | first anti snakebite and hepatoprotective characterization of a trypsin kunitz like inhibitor ecti from the plant i enterolobium contortisiliquum i a case of two soul mates meeting |
| topic | serine protease Cdtsp-2 Kunitz-type inhibitor <i>Crotalus durissus terrificus</i> |
| url | https://www.mdpi.com/1424-8247/16/4/632 |
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