Varanid Lizard Venoms Disrupt the Clotting Ability of Human Fibrinogen through Destructive Cleavage

The functional activities of Anguimorpha lizard venoms have received less attention compared to serpent lineages. Bite victims of varanid lizards often report persistent bleeding exceeding that expected for the mechanical damage of the bite. Research to date has identified the blockage of platelet a...

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Main Authors: James S. Dobson, Christina N. Zdenek, Chris Hay, Aude Violette, Rudy Fourmy, Chip Cochran, Bryan G. Fry
Format: Article
Language:English
Published: MDPI AG 2019-05-01
Series:Toxins
Subjects:
Online Access:https://www.mdpi.com/2072-6651/11/5/255
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author James S. Dobson
Christina N. Zdenek
Chris Hay
Aude Violette
Rudy Fourmy
Chip Cochran
Bryan G. Fry
author_facet James S. Dobson
Christina N. Zdenek
Chris Hay
Aude Violette
Rudy Fourmy
Chip Cochran
Bryan G. Fry
author_sort James S. Dobson
collection DOAJ
description The functional activities of Anguimorpha lizard venoms have received less attention compared to serpent lineages. Bite victims of varanid lizards often report persistent bleeding exceeding that expected for the mechanical damage of the bite. Research to date has identified the blockage of platelet aggregation as one bleeding-inducing activity, and destructive cleavage of fibrinogen as another. However, the ability of the venoms to prevent clot formation has not been directly investigated. Using a thromboelastograph (TEG5000), clot strength was measured after incubating human fibrinogen with <i>Heloderma</i> and <i>Varanus</i> lizard venoms. Clot strengths were found to be highly variable, with the most potent effects produced by incubation with <i>Varanus</i> venoms from the <i>Odatria</i> and <i>Euprepriosaurus</i> clades. The most fibrinogenolytically active venoms belonged to arboreal species and therefore prey escape potential is likely a strong evolutionary selection pressure. The results are also consistent with reports of profusive bleeding from bites from other notably fibrinogenolytic species, such as <i>V. giganteus</i>. Our results provide evidence in favour of the predatory role of venom in varanid lizards, thus shedding light on the evolution of venom in reptiles and revealing potential new sources of bioactive molecules useful as lead compounds in drug design and development.
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spelling doaj.art-784a69d0048f433fb53fc262ce18f28d2022-12-22T02:57:45ZengMDPI AGToxins2072-66512019-05-0111525510.3390/toxins11050255toxins11050255Varanid Lizard Venoms Disrupt the Clotting Ability of Human Fibrinogen through Destructive CleavageJames S. Dobson0Christina N. Zdenek1Chris Hay2Aude Violette3Rudy Fourmy4Chip Cochran5Bryan G. Fry6Venom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, QLD 4072, AustraliaVenom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, QLD 4072, AustraliaVenom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, QLD 4072, AustraliaAlphabiotoxine Laboratory sprl, Barberie 15, 7911 Montroeul-au-bois, BelgiumAlphabiotoxine Laboratory sprl, Barberie 15, 7911 Montroeul-au-bois, BelgiumDepartment of Earth and Biological Sciences, Loma Linda University, Loma Linda, CA 92350, USAVenom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, QLD 4072, AustraliaThe functional activities of Anguimorpha lizard venoms have received less attention compared to serpent lineages. Bite victims of varanid lizards often report persistent bleeding exceeding that expected for the mechanical damage of the bite. Research to date has identified the blockage of platelet aggregation as one bleeding-inducing activity, and destructive cleavage of fibrinogen as another. However, the ability of the venoms to prevent clot formation has not been directly investigated. Using a thromboelastograph (TEG5000), clot strength was measured after incubating human fibrinogen with <i>Heloderma</i> and <i>Varanus</i> lizard venoms. Clot strengths were found to be highly variable, with the most potent effects produced by incubation with <i>Varanus</i> venoms from the <i>Odatria</i> and <i>Euprepriosaurus</i> clades. The most fibrinogenolytically active venoms belonged to arboreal species and therefore prey escape potential is likely a strong evolutionary selection pressure. The results are also consistent with reports of profusive bleeding from bites from other notably fibrinogenolytic species, such as <i>V. giganteus</i>. Our results provide evidence in favour of the predatory role of venom in varanid lizards, thus shedding light on the evolution of venom in reptiles and revealing potential new sources of bioactive molecules useful as lead compounds in drug design and development.https://www.mdpi.com/2072-6651/11/5/255Anguimorpha<i>Varanus</i><i>Heloderma</i>lizard venomfibrinogenolyticanticoagulation
spellingShingle James S. Dobson
Christina N. Zdenek
Chris Hay
Aude Violette
Rudy Fourmy
Chip Cochran
Bryan G. Fry
Varanid Lizard Venoms Disrupt the Clotting Ability of Human Fibrinogen through Destructive Cleavage
Toxins
Anguimorpha
<i>Varanus</i>
<i>Heloderma</i>
lizard venom
fibrinogenolytic
anticoagulation
title Varanid Lizard Venoms Disrupt the Clotting Ability of Human Fibrinogen through Destructive Cleavage
title_full Varanid Lizard Venoms Disrupt the Clotting Ability of Human Fibrinogen through Destructive Cleavage
title_fullStr Varanid Lizard Venoms Disrupt the Clotting Ability of Human Fibrinogen through Destructive Cleavage
title_full_unstemmed Varanid Lizard Venoms Disrupt the Clotting Ability of Human Fibrinogen through Destructive Cleavage
title_short Varanid Lizard Venoms Disrupt the Clotting Ability of Human Fibrinogen through Destructive Cleavage
title_sort varanid lizard venoms disrupt the clotting ability of human fibrinogen through destructive cleavage
topic Anguimorpha
<i>Varanus</i>
<i>Heloderma</i>
lizard venom
fibrinogenolytic
anticoagulation
url https://www.mdpi.com/2072-6651/11/5/255
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