Neutralization of the haemorrhagic activities of viperine snake venoms and venom metalloproteinases using synthetic peptide inhibitors and chelators
Envenoming by the West African saw-scaled viper, Echis ocellatus resembles that of most vipers, in that it results in local blistering, necrosis and sometimes life-threatening systemic haemorrhage. While effective against systemic envenoming, current antivenoms have little or no effect against local...
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| Veröffentlicht in: | Toxicon (Oxford) 2007-04, Vol.49 (5), p.734-739 |
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| creator | Howes, J.-M. Theakston, R.D.G. Laing, G.D. |
| description | Envenoming by the West African saw-scaled viper,
Echis ocellatus resembles that of most vipers, in that it results in local blistering, necrosis and sometimes life-threatening systemic haemorrhage. While effective against systemic envenoming, current antivenoms have little or no effect against local tissue damage. The major mediators of local venom pathology are the zinc-dependant snake venom metalloproteinases (SVMPs). The high degree of structural and functional homology between SVMPs and their mammalian relatives the matrix metalloproteinases (MMPs) suggests that substrate/inhibitor interactions between these subfamilies are likely to be analogous. In this study, four recently developed MMP inhibitors (MMPIs) (Marimastat, AG-3340, CGS-270 23A and Bay-12 9566) are evaluated in addition to three metal ion chelators (EDTA, TPEN and BAPTA) for their ability to inhibit the haemorrhagic activities of the medically important
E. ocellatus venom and one of its haemorrhagic SVMPs, EoVMP2. As expected, the metal ion chelators significantly inhibited the haemorrhagic activities of both whole
E. ocellatus venom and EoVMP2, while the synthetic MMPIs show more variation in their efficacies. These variations suggest that individual MMPIs show specificity towards SVMPs and that their application to the neutralization of local haemorrhage may require a synthetic MMPI mixture, ensuring that a close structural component for each SVMP is represented. |
| doi_str_mv | 10.1016/j.toxicon.2006.11.020 |
| format | Article |
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Echis ocellatus resembles that of most vipers, in that it results in local blistering, necrosis and sometimes life-threatening systemic haemorrhage. While effective against systemic envenoming, current antivenoms have little or no effect against local tissue damage. The major mediators of local venom pathology are the zinc-dependant snake venom metalloproteinases (SVMPs). The high degree of structural and functional homology between SVMPs and their mammalian relatives the matrix metalloproteinases (MMPs) suggests that substrate/inhibitor interactions between these subfamilies are likely to be analogous. In this study, four recently developed MMP inhibitors (MMPIs) (Marimastat, AG-3340, CGS-270 23A and Bay-12 9566) are evaluated in addition to three metal ion chelators (EDTA, TPEN and BAPTA) for their ability to inhibit the haemorrhagic activities of the medically important
E. ocellatus venom and one of its haemorrhagic SVMPs, EoVMP2. As expected, the metal ion chelators significantly inhibited the haemorrhagic activities of both whole
E. ocellatus venom and EoVMP2, while the synthetic MMPIs show more variation in their efficacies. These variations suggest that individual MMPIs show specificity towards SVMPs and that their application to the neutralization of local haemorrhage may require a synthetic MMPI mixture, ensuring that a close structural component for each SVMP is represented.</description><identifier>ISSN: 0041-0101</identifier><identifier>EISSN: 1879-3150</identifier><identifier>DOI: 10.1016/j.toxicon.2006.11.020</identifier><identifier>PMID: 17196631</identifier><identifier>CODEN: TOXIA6</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Animal poisons toxicology. Antivenoms ; Animals ; Biological and medical sciences ; Biphenyl Compounds ; Chelating Agents - pharmacology ; Chelating Agents - therapeutic use ; Chelator ; Chromatography, Gel ; Chromatography, Liquid ; Echis ; Edetic Acid - pharmacology ; Edetic Acid - therapeutic use ; Egtazic Acid - analogs & derivatives ; Egtazic Acid - pharmacology ; Egtazic Acid - therapeutic use ; Ethylenediamines - pharmacology ; Ethylenediamines - therapeutic use ; Evaluation Studies as Topic ; Haemorrhagic activity ; Hemorrhage - etiology ; Hemorrhage - prevention & control ; Hydroxamic Acids - pharmacology ; Hydroxamic Acids - therapeutic use ; Medical sciences ; Metalloproteases - antagonists & inhibitors ; Metalloproteases - toxicity ; Metalloproteinase ; Mice ; Molecular Structure ; Organic Chemicals - pharmacology ; Organic Chemicals - therapeutic use ; Peptide inhibitor ; Phenylbutyrates ; Protein Kinase Inhibitors - pharmacology ; Protein Kinase Inhibitors - therapeutic use ; Pyrazines - pharmacology ; Pyrazines - therapeutic use ; Snake Bites - complications ; Snake Bites - drug therapy ; Snake venom ; Statistics, Nonparametric ; Sulfonamides - pharmacology ; Sulfonamides - therapeutic use ; Toxicology ; Viper Venoms - antagonists & inhibitors ; Viper Venoms - toxicity</subject><ispartof>Toxicon (Oxford), 2007-04, Vol.49 (5), p.734-739</ispartof><rights>2006 Elsevier Ltd</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c490t-e416ced91f9a900689c6868d7a1140b05cefcdc49edce05616eb6ff58adf5ece3</citedby><cites>FETCH-LOGICAL-c490t-e416ced91f9a900689c6868d7a1140b05cefcdc49edce05616eb6ff58adf5ece3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0041010106004430$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18772853$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17196631$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Howes, J.-M.</creatorcontrib><creatorcontrib>Theakston, R.D.G.</creatorcontrib><creatorcontrib>Laing, G.D.</creatorcontrib><title>Neutralization of the haemorrhagic activities of viperine snake venoms and venom metalloproteinases using synthetic peptide inhibitors and chelators</title><title>Toxicon (Oxford)</title><addtitle>Toxicon</addtitle><description>Envenoming by the West African saw-scaled viper,
Echis ocellatus resembles that of most vipers, in that it results in local blistering, necrosis and sometimes life-threatening systemic haemorrhage. While effective against systemic envenoming, current antivenoms have little or no effect against local tissue damage. The major mediators of local venom pathology are the zinc-dependant snake venom metalloproteinases (SVMPs). The high degree of structural and functional homology between SVMPs and their mammalian relatives the matrix metalloproteinases (MMPs) suggests that substrate/inhibitor interactions between these subfamilies are likely to be analogous. In this study, four recently developed MMP inhibitors (MMPIs) (Marimastat, AG-3340, CGS-270 23A and Bay-12 9566) are evaluated in addition to three metal ion chelators (EDTA, TPEN and BAPTA) for their ability to inhibit the haemorrhagic activities of the medically important
E. ocellatus venom and one of its haemorrhagic SVMPs, EoVMP2. As expected, the metal ion chelators significantly inhibited the haemorrhagic activities of both whole
E. ocellatus venom and EoVMP2, while the synthetic MMPIs show more variation in their efficacies. These variations suggest that individual MMPIs show specificity towards SVMPs and that their application to the neutralization of local haemorrhage may require a synthetic MMPI mixture, ensuring that a close structural component for each SVMP is represented.</description><subject>Animal poisons toxicology. Antivenoms</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biphenyl Compounds</subject><subject>Chelating Agents - pharmacology</subject><subject>Chelating Agents - therapeutic use</subject><subject>Chelator</subject><subject>Chromatography, Gel</subject><subject>Chromatography, Liquid</subject><subject>Echis</subject><subject>Edetic Acid - pharmacology</subject><subject>Edetic Acid - therapeutic use</subject><subject>Egtazic Acid - analogs & derivatives</subject><subject>Egtazic Acid - pharmacology</subject><subject>Egtazic Acid - therapeutic use</subject><subject>Ethylenediamines - pharmacology</subject><subject>Ethylenediamines - therapeutic use</subject><subject>Evaluation Studies as Topic</subject><subject>Haemorrhagic activity</subject><subject>Hemorrhage - etiology</subject><subject>Hemorrhage - prevention & control</subject><subject>Hydroxamic Acids - pharmacology</subject><subject>Hydroxamic Acids - therapeutic use</subject><subject>Medical sciences</subject><subject>Metalloproteases - antagonists & inhibitors</subject><subject>Metalloproteases - toxicity</subject><subject>Metalloproteinase</subject><subject>Mice</subject><subject>Molecular Structure</subject><subject>Organic Chemicals - pharmacology</subject><subject>Organic Chemicals - therapeutic use</subject><subject>Peptide inhibitor</subject><subject>Phenylbutyrates</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Protein Kinase Inhibitors - therapeutic use</subject><subject>Pyrazines - pharmacology</subject><subject>Pyrazines - therapeutic use</subject><subject>Snake Bites - complications</subject><subject>Snake Bites - drug therapy</subject><subject>Snake venom</subject><subject>Statistics, Nonparametric</subject><subject>Sulfonamides - pharmacology</subject><subject>Sulfonamides - therapeutic use</subject><subject>Toxicology</subject><subject>Viper Venoms - antagonists & inhibitors</subject><subject>Viper Venoms - toxicity</subject><issn>0041-0101</issn><issn>1879-3150</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFu1DAURS0EokPhE0DewC7Bb5I4yQqhigJSBZt2bXmcl-YNiR1sZ0T5Dj64HiVSl6xsy-deP9_L2FsQOQiQH495dH_IOJvvhZA5QC724hnbQVO3WQGVeM52QpSQiYRfsFchHIUQRdPKl-wCamilLGDH_v3AJXo90l8dyVnueh4H5IPGyXk_6HsyXJtIJ4qE4Xx9ohk9WeTB6l_IT2jdFLi23brlE0Y9jm72LiJZHZJqCWTveXiwyTomwxnnSB1ysgMdKDq_6s2Aoz6fXrMXvR4DvtnWS3Z3_eX26lt28_Pr96vPN5kpWxEzLEEa7FroW92mEJrWyEY2Xa0BSnEQlcHedInFzqCoJEg8yL6vGt31FRosLtmH1TcN-3vBENVEweA4aotuCSqF1FZ1WSawWkHjXQgeezV7mrR_UCDUuQ51VFsd6lyHAlCpjqR7tz2wHCbsnlRb_gl4vwE6GD32XltD4Ylr6nrfVEXiPq0cpjhOhF4FQ2jT78mjiapz9J9RHgFMdLGf</recordid><startdate>20070401</startdate><enddate>20070401</enddate><creator>Howes, J.-M.</creator><creator>Theakston, R.D.G.</creator><creator>Laing, G.D.</creator><general>Elsevier Ltd</general><general>Elsevier Science</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>20070401</creationdate><title>Neutralization of the haemorrhagic activities of viperine snake venoms and venom metalloproteinases using synthetic peptide inhibitors and chelators</title><author>Howes, J.-M. ; Theakston, R.D.G. ; Laing, G.D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c490t-e416ced91f9a900689c6868d7a1140b05cefcdc49edce05616eb6ff58adf5ece3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animal poisons toxicology. Antivenoms</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Biphenyl Compounds</topic><topic>Chelating Agents - pharmacology</topic><topic>Chelating Agents - therapeutic use</topic><topic>Chelator</topic><topic>Chromatography, Gel</topic><topic>Chromatography, Liquid</topic><topic>Echis</topic><topic>Edetic Acid - pharmacology</topic><topic>Edetic Acid - therapeutic use</topic><topic>Egtazic Acid - analogs & derivatives</topic><topic>Egtazic Acid - pharmacology</topic><topic>Egtazic Acid - therapeutic use</topic><topic>Ethylenediamines - pharmacology</topic><topic>Ethylenediamines - therapeutic use</topic><topic>Evaluation Studies as Topic</topic><topic>Haemorrhagic activity</topic><topic>Hemorrhage - etiology</topic><topic>Hemorrhage - prevention & control</topic><topic>Hydroxamic Acids - pharmacology</topic><topic>Hydroxamic Acids - therapeutic use</topic><topic>Medical sciences</topic><topic>Metalloproteases - antagonists & inhibitors</topic><topic>Metalloproteases - toxicity</topic><topic>Metalloproteinase</topic><topic>Mice</topic><topic>Molecular Structure</topic><topic>Organic Chemicals - pharmacology</topic><topic>Organic Chemicals - therapeutic use</topic><topic>Peptide inhibitor</topic><topic>Phenylbutyrates</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Protein Kinase Inhibitors - therapeutic use</topic><topic>Pyrazines - pharmacology</topic><topic>Pyrazines - therapeutic use</topic><topic>Snake Bites - complications</topic><topic>Snake Bites - drug therapy</topic><topic>Snake venom</topic><topic>Statistics, Nonparametric</topic><topic>Sulfonamides - pharmacology</topic><topic>Sulfonamides - therapeutic use</topic><topic>Toxicology</topic><topic>Viper Venoms - antagonists & inhibitors</topic><topic>Viper Venoms - toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Howes, J.-M.</creatorcontrib><creatorcontrib>Theakston, R.D.G.</creatorcontrib><creatorcontrib>Laing, G.D.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Toxicon (Oxford)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Howes, J.-M.</au><au>Theakston, R.D.G.</au><au>Laing, G.D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neutralization of the haemorrhagic activities of viperine snake venoms and venom metalloproteinases using synthetic peptide inhibitors and chelators</atitle><jtitle>Toxicon (Oxford)</jtitle><addtitle>Toxicon</addtitle><date>2007-04-01</date><risdate>2007</risdate><volume>49</volume><issue>5</issue><spage>734</spage><epage>739</epage><pages>734-739</pages><issn>0041-0101</issn><eissn>1879-3150</eissn><coden>TOXIA6</coden><abstract>Envenoming by the West African saw-scaled viper,
Echis ocellatus resembles that of most vipers, in that it results in local blistering, necrosis and sometimes life-threatening systemic haemorrhage. While effective against systemic envenoming, current antivenoms have little or no effect against local tissue damage. The major mediators of local venom pathology are the zinc-dependant snake venom metalloproteinases (SVMPs). The high degree of structural and functional homology between SVMPs and their mammalian relatives the matrix metalloproteinases (MMPs) suggests that substrate/inhibitor interactions between these subfamilies are likely to be analogous. In this study, four recently developed MMP inhibitors (MMPIs) (Marimastat, AG-3340, CGS-270 23A and Bay-12 9566) are evaluated in addition to three metal ion chelators (EDTA, TPEN and BAPTA) for their ability to inhibit the haemorrhagic activities of the medically important
E. ocellatus venom and one of its haemorrhagic SVMPs, EoVMP2. As expected, the metal ion chelators significantly inhibited the haemorrhagic activities of both whole
E. ocellatus venom and EoVMP2, while the synthetic MMPIs show more variation in their efficacies. These variations suggest that individual MMPIs show specificity towards SVMPs and that their application to the neutralization of local haemorrhage may require a synthetic MMPI mixture, ensuring that a close structural component for each SVMP is represented.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>17196631</pmid><doi>10.1016/j.toxicon.2006.11.020</doi><tpages>6</tpages></addata></record> |
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| issn | 0041-0101 1879-3150 |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animal poisons toxicology. Antivenoms Animals Biological and medical sciences Biphenyl Compounds Chelating Agents - pharmacology Chelating Agents - therapeutic use Chelator Chromatography, Gel Chromatography, Liquid Echis Edetic Acid - pharmacology Edetic Acid - therapeutic use Egtazic Acid - analogs & derivatives Egtazic Acid - pharmacology Egtazic Acid - therapeutic use Ethylenediamines - pharmacology Ethylenediamines - therapeutic use Evaluation Studies as Topic Haemorrhagic activity Hemorrhage - etiology Hemorrhage - prevention & control Hydroxamic Acids - pharmacology Hydroxamic Acids - therapeutic use Medical sciences Metalloproteases - antagonists & inhibitors Metalloproteases - toxicity Metalloproteinase Mice Molecular Structure Organic Chemicals - pharmacology Organic Chemicals - therapeutic use Peptide inhibitor Phenylbutyrates Protein Kinase Inhibitors - pharmacology Protein Kinase Inhibitors - therapeutic use Pyrazines - pharmacology Pyrazines - therapeutic use Snake Bites - complications Snake Bites - drug therapy Snake venom Statistics, Nonparametric Sulfonamides - pharmacology Sulfonamides - therapeutic use Toxicology Viper Venoms - antagonists & inhibitors Viper Venoms - toxicity |
| title | Neutralization of the haemorrhagic activities of viperine snake venoms and venom metalloproteinases using synthetic peptide inhibitors and chelators |
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