Clinical implications of ontogenetic differences in the coagulotoxic activity of Bothrops jararacussu venoms

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dc.contributorLab. Herpetologiapt_BR
dc.contributorLab. Imunopatologiapt_BR
dc.contributorLECZ - Laboratório de Coleções Zoológicaspt_BR
dc.contributor.authorFabri, Carolinept_BR
dc.contributor.authorZdenek, Christina N.pt_BR
dc.contributor.authorBourke, Lachlan A.pt_BR
dc.contributor.authorSeneci, Lorenzopt_BR
dc.contributor.authorChowdhury, Abhinandanpt_BR
dc.contributor.authorFreitas-de-Sousa, Luciana Aparecidapt_BR
dc.contributor.authorMenezes, Frederico de Alcântarapt_BR
dc.contributor.authorMoura-da-Silva, Ana Mariapt_BR
dc.contributor.authorTanaka-Azevedo, Anita Miticopt_BR
dc.contributor.authorFry, Bryan G.pt_BR
dc.identifier.citationFabri C, Zdenek CN., Bourke LA., Seneci L, Chowdhury A, Freitas-de-Sousa LA, et al. Clinical implications of ontogenetic differences in the coagulotoxic activity of Bothrops jararacussu venoms. Toxicol. Lett.. 2021 Sept;348:59-72. doi:10.1016/j.toxlet.2021.05.005.pt_BR
dc.description.abstractIs snake venom activity influenced by size? This is a long-standing question that can have important consequences for the treatment of snake envenomation. Ontogenetic shifts in venom composition are a well-documented characteristic of numerous snake species. Although snake venoms can cause a range of pathophysiological disturbances, establishing the coagulotoxic profiles related to such shifts is a justified approach because coagulotoxicity can be deadly, and its neutralisation is a challenge for current antivenom therapy. Thus, we aimed to assess the coagulotoxicity patterns on plasma and fibrinogen produced by B. jararacussu venoms from individuals of different sizes and sex, and the neutralisation potential of SAB (anti bothropic serum produced by Butantan Institute). The use of a metalloproteinase inhibitor (Prinomastat) and a serine proteinase inhibitor (AEBSF) enabled us to determine the toxin class responsible for the observed coagulopathy: activity on plasma was found to be metalloprotease driven, while the activity on fibrinogen is serine protease driven. To further explore differences in venom activity, the activation of Factor X and prothrombin by as a function of snake size was also evaluated. All the venoms exhibited a potent procoagulant effect upon plasma and were less potent in their pseudo-procoagulant clotting effect upon fibrinogen. On human plasma, the venoms from smaller snakes produced more rapid clotting than the larger ones. In contrast, the venom activity on fibrinogen had no relation with size or sex. The difference in procoagulant potency was correlated with the bigger snakes being proportionally better neutralized by antivenom due to the lower levels of procoagulant toxins, than the smaller. Thus, while the antivenom ultimately neutralized the venoms, proportionally more would be needed for an equal mass of venom from a small snake than a large one. Similarly, the neutralisation by SAB of the pseudo-procoagulant clotting effects was also correlated with relative potency, with the smaller and bigger snakes being neutralized proportional to potency, but with no correlation to size. Thromboelastography (TEG) tests on human and toad plasma revealed that small snakes’ venoms acted quicker than large snakes’ venom on both plasmas, with the action upon amphibian plasma consistent with smaller snakes taking a larger proportion of anuran prey than adults. Altogether, the ontogenetic differences regarding coagulotoxic potency and corresponding impact upon relative antivenom neutralisation of snakes with different sizes were shown, underscores the medical importance of investigating ontogenetic changes in order to provide data crucial for evidence-based design of clinical management strategies.pt_BR
dc.description.sponsorshipAustralian Research Council (ARC)pt_BR
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)pt_BR
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado do Amazonas (FAPEAM)pt_BR
dc.relation.ispartofToxicology Letterspt_BR
dc.rightsRestricted Accesspt_BR
dc.titleClinical implications of ontogenetic differences in the coagulotoxic activity of Bothrops jararacussu venomspt_BR
dc.contributor.externalUniversity of Queensland (UQ)pt_BR
dc.contributor.externalLeiden Universitypt_BR
dc.contributor.externalFundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD)pt_BR
dc.subject.keywordB. jararacussupt_BR
dc.subject.keywordAntivenom neutralisationpt_BR
dc.relation.ispartofabbreviatedToxicol. Lett.pt_BR
dc.identifier.citationabntv. 348, p. 59-72, set. 2021pt_BR
dc.identifier.citationvancouver2021 Sept;348:59-72pt_BR
dc.contributor.butantanFabri, Caroline|:Aluno|:Lab. Herpetologia:PrimeiroAutorpt_BR
dc.contributor.butantanFreitas-de-Sousa, Luciana Aparecida|:Aluno|:Lab. Imunopatologiapt_BR
dc.contributor.butantanMenezes, Frederico de Alcântara|:Aluno|:LECZ - Laboratório de Coleções Zoológicaspt_BR
dc.contributor.butantanMoura-da-Silva, Ana Maria|:Pesquisador:Docente permanente PPGTOX|:Lab. Imunopatologiapt_BR
dc.contributor.butantanTanaka-Azevedo, Anita Mitico|:Pesquisador|:Lab. Herpetologiapt_BR
dc.sponsorship.butantanAustralian Research Council (ARC)¦¦DP190100304pt_BR
dc.sponsorship.butantanCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)¦¦001pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2016/50127-5pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado do Amazonas (FAPEAM)¦¦pt_BR
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