Toxicon: X最新文献

{"title":"In vitro and in vivo preclinical venom inhibition assays identify metalloproteinase inhibiting drugs as potential future treatments for snakebite envenoming by Dispholidus typus","authors":"Stefanie K. Menzies ,&nbsp;Rachel H. Clare ,&nbsp;Chunfang Xie ,&nbsp;Adam Westhorpe ,&nbsp;Steven R. Hall ,&nbsp;Rebecca J. Edge ,&nbsp;Jaffer Alsolaiss ,&nbsp;Edouard Crittenden ,&nbsp;Amy E. Marriott ,&nbsp;Robert A. Harrison ,&nbsp;Jeroen Kool ,&nbsp;Nicholas R. Casewell","doi":"10.1016/j.toxcx.2022.100118","DOIUrl":"https://doi.org/10.1016/j.toxcx.2022.100118","url":null,"abstract":"<div><p>Snakebite envenoming affects more than 250,000 people annually in sub-Saharan Africa. Envenoming by <em>Dispholidus typus</em> (boomslang) results in venom-induced consumption coagulopathy (VICC), whereby highly abundant prothrombin-activating snake venom metalloproteinases (SVMPs) consume clotting factors and deplete fibrinogen. The only available treatment for <em>D. typus</em> envenoming is the monovalent SAIMR Boomslang antivenom. Treatment options are urgently required because this antivenom is often difficult to source and, at US$6000/vial, typically unaffordable for most snakebite patients. We therefore investigated the <em>in vitro</em> and <em>in vivo</em> preclinical efficacy of four SVMP inhibitors to neutralise the effects of <em>D. typus</em> venom; the matrix metalloproteinase inhibitors marimastat and prinomastat, and the metal chelators dimercaprol and DMPS<em>.</em> The venom of <em>D. typus</em> exhibited an SVMP-driven procoagulant phenotype <em>in vitro</em>. Marimastat and prinomastat demonstrated equipotent inhibition of the SVMP-mediated procoagulant activity of the venom <em>in vitro</em>, whereas dimercaprol and DMPS showed considerably lower potency. However, when tested in preclinical murine models of envenoming using mixed sex CD1 mice, DMPS and marimastat demonstrated partial protection against venom lethality, demonstrated by prolonged survival times of experimental animals, whereas dimercaprol and prinomastat failed to confer any protection at the doses tested. The preclinical results presented here demonstrate that DMPS and marimastat show potential as novel small molecule-based therapeutics for <em>D. typus</em> snakebite envenoming. These two drugs have been previously shown to be effective against <em>Echis ocellatus</em> VICC in preclinical models, and thus we conclude that marimastat and DMPS should be further explored as potentially valuable early intervention therapeutics to broadly treat VICC following snakebite envenoming in sub-Saharan Africa.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"14 ","pages":"Article 100118"},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171022000285/pdfft?md5=208c541ca8bd1a7377592109b6e10d09&pid=1-s2.0-S2590171022000285-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92095876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profiling hymenopteran venom toxins: Protein families, structural landscape, biological activities, and pharmacological benefits","authors":"Juan Carlos Guido-Patiño ,&nbsp;Fabien Plisson","doi":"10.1016/j.toxcx.2022.100119","DOIUrl":"10.1016/j.toxcx.2022.100119","url":null,"abstract":"<div><p>Hymenopterans are an untapped source of venom secretions. Their recent proteo-transcriptomic studies have revealed an extraordinary pool of toxins that participate in various biological processes, including pain, paralysis, allergic reactions, and antimicrobial activities. Comprehensive and clade-specific campaigns to collect hymenopteran venoms are therefore needed. We consider that data-driven bioprospecting may help prioritise sampling and alleviate associated costs. This work established the current protein landscape from hymenopteran venoms to evaluate possible sample bias by studying their origins, sequence diversity, known structures, and biological functions. We collected all 282 reported hymenopteran toxins (peptides and proteins) from the UniProt database that we clustered into 21 protein families from the three studied clades - wasps, bees, and ants. We identified 119 biological targets of hymenopteran toxins ranging from pathogen membranes to eukaryotic proteases, ion channels and protein receptors. Our systematic study further extended to hymenopteran toxins' therapeutic and biotechnological values, where we revealed promising applications in crop pests, human infections, autoimmune diseases, and neurodegenerative disorders.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"14 ","pages":"Article 100119"},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171022000297/pdfft?md5=02a7ddd19385c79beb148abded09d3a6&pid=1-s2.0-S2590171022000297-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45369393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An investigation into the toxicity of tissue extracts from two distinct marine Polychaeta","authors":"Mariaelena D'Ambrosio ,&nbsp;Íris Ramos ,&nbsp;Carla Martins ,&nbsp;Pedro M. Costa","doi":"10.1016/j.toxcx.2022.100116","DOIUrl":"10.1016/j.toxcx.2022.100116","url":null,"abstract":"<div><p>The present study investigated the potential toxicity of venomous secretions of two polychaetes, <em>Hediste diversicolor</em> and <em>Glycera alba</em> (Annelida: Phyllodocida). Toxic activity of putative toxins, measured on mussel gills through the Comet assay, revealed higher effects caused by extracts from <em>H. diversicolor</em> skin and <em>G. alba</em> specialised, jawed proboscis, when compared to control. The results suggest that <em>H</em>. <em>diversicolor</em> secretes toxins via skin for protection against predators, contrarily to <em>G. alba</em>, who secretes toxins for predation.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"14 ","pages":"Article 100116"},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171022000261/pdfft?md5=77b86e2b571fa5bdd143efb9a1697f05&pid=1-s2.0-S2590171022000261-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42337875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicon and Toxicon: X – 2022 and beyond","authors":"Raymond S. Norton ,&nbsp;Denise V. Tambourgi","doi":"10.1016/j.toxcx.2022.100098","DOIUrl":"10.1016/j.toxcx.2022.100098","url":null,"abstract":"","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"13 ","pages":"Article 100098"},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1d/5d/main.PMC8844711.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39948819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Verified envenomations by crevice weaver spiders (genus Kukulcania): Bites are of minor expression but the spiders are commonly misidentified as medically important brown recluses (genus Loxosceles) in North America","authors":"Richard S. Vetter","doi":"10.1016/j.toxcx.2022.100091","DOIUrl":"10.1016/j.toxcx.2022.100091","url":null,"abstract":"<div><p>From southern North America, five verified bites by crevice weaver spiders, <em>Kukulcania</em> spp. (Filistatidae), are presented here, three of which are pediatric cases. Although the envenomation manifestations were of minimal expression, the salient aspect of this report is that <em>Kukulcania</em> spiders are frequently misidentified as brown recluse spiders (genus <em>Loxosceles</em>) which are infamous for causing serious dermonecrosis and rarely, life-threatening systemic effects. Misidentification of this relatively harmless spider as a medically important recluse when presented to a physician in an envenomation episode could lead to unwarranted and overzealous treatment such as contraindicated debridement of the affected area.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"13 ","pages":"Article 100091"},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8789574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39879613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A transdisciplinary approach to snakebite envenoming","authors":"Rafael Ruiz de Castañeda ,&nbsp;Isabelle Bolon ,&nbsp;José María Gutiérrez","doi":"10.1016/j.toxcx.2021.100088","DOIUrl":"10.1016/j.toxcx.2021.100088","url":null,"abstract":"","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"13 ","pages":"Article 100088"},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39891921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Behaviour of the Sydney funnel-web spider Atrax robustus over different contexts, time, and stimuli","authors":"Linda Hernández Duran ,&nbsp;David Thomas Wilson ,&nbsp;Tasmin Lee Rymer","doi":"10.1016/j.toxcx.2022.100093","DOIUrl":"https://doi.org/10.1016/j.toxcx.2022.100093","url":null,"abstract":"<div><p><em>Atrax robustus</em> is an iconic Australian spider because the venom can be lethal to humans. Moreover, some of the venom biomolecules have promise as therapeutic and bioinsecticidal leads. Nonetheless, aspects related to the life history and behaviour of this species, which might influence changes in venom components, have been overlooked. We assessed different behavioural traits (antipredator behaviour, defensiveness and activity) of juveniles and adult females across different contexts (predation, conspecific tolerance and exploration of a new territory) and stimuli (puff of air versus prod) over time. Adults responded to a puff of air faster than juveniles, but in response to a prod, both juveniles and adults become more defensive over time. No differences were observed between adults and juveniles for conspecific tolerance and exploration. Understanding behaviour of venomous species is important because behaviours may affect physiological traits, such as venom, and the ability of spiders to adapt to different conditions.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"13 ","pages":"Article 100093"},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171022000030/pdfft?md5=1eccf8013ff220686ada70e83b6a3dfc&pid=1-s2.0-S2590171022000030-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92167674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implications of bleaching on cnidarian venom ecology","authors":"K.L. Kaposi ,&nbsp;R.L. Courtney ,&nbsp;J.E. Seymour","doi":"10.1016/j.toxcx.2022.100094","DOIUrl":"10.1016/j.toxcx.2022.100094","url":null,"abstract":"<div><p>Cnidarian bleaching research often focuses on the effects on a cnidarian's physiological health and fitness, whilst little focus has been towards the impacts of these events on their venom ecology. Given the importance of a cnidarian's venom to their survival and the increasing threat of bleaching events, it is important to understand the effects that this threat may have on this important aspect of their ecology as it may have unforeseen impacts on their ability to catch prey and defend themselves. This review aims to explore evidence that suggests that bleaching may impact on each of the key aspects of a cnidarians' venom ecology: cnidae, venom composition, and venom toxicity. Additionally, the resulting energy deficit, compensatory heterotrophic feeding, and increased defensive measures have been highlighted as possible ecological factors driving these changes. Suggestions are also made to guide the success of research in this field into the future, specifically in regards to selecting a study organism, the importance of accurate symbiont and cnidae identification, use of appropriate bleaching methods, determination of bleaching, and animal handling. Ultimately, this review highlights a significant and important gap in our knowledge into how cnidarians are, and will, continue to be impacted by bleaching stress.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"13 ","pages":"Article 100094"},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/45/e1/main.PMC8819380.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39614364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Snakebite envenoming in humanitarian crises and migration: A scoping review and the Médecins Sans Frontières experience","authors":"Gabriel Alcoba ,&nbsp;Julien Potet ,&nbsp;Renaud Vatrinet ,&nbsp;Saschveen Singh ,&nbsp;Carolina Nanclares ,&nbsp;Alexandra Kruse ,&nbsp;Margriet Den Boer ,&nbsp;Lucas Molfino ,&nbsp;Koert Ritmeijer","doi":"10.1016/j.toxcx.2021.100089","DOIUrl":"10.1016/j.toxcx.2021.100089","url":null,"abstract":"<div><p>Snakebite envenoming is a public health concern in many countries affected by humanitarian crises. Its magnitude was recognized internationally but associations between snakebite peaks and humanitarian crises were never clearly established or analysed. This scoping review searched any available evidence of this hypothesized association between snakebite types of crises, through PubMed/Medline by two researchers. The search also included hand searching, and reports from humanitarian organizations working in this area.</p><p>The scoping review yielded 41 results. None described a robust epidemiological link or evidence of causality. There is an evidence gap regarding our research question. Several publications however point or hint towards the occurrence of snakebite outbreaks during conflict, displacement, floods, and migration of impoverished agricultural workers. Non-systematic screening yielded another 11 publications (52 in total). We found Médecins Sans Frontières routine reports showing that 6469 patients were admitted in 2019 throughout its projects in 17 countries. The impact of snakebite was the highest in four countries particularly affected by humanitarian crises, South Sudan, Ethiopia, Central African Republic, and Yemen, with some hospitals receiving more than 1000 annual admissions. Time correlations with conflict and events are shown in Figures. We found no published epidemiological data formally showing any associations between humanitarian crises and snakebite incidence. However, the search publications showing peaks during crises, and monitoring curves in four countries point towards an increased risk during humanitarian crises.</p><p>We call for urgent population-based studies and surveillance. Stakeholders should consider upgrading snakebite care and antivenom supply during humanitarian crises in snakebite-endemic countries.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"13 ","pages":"Article 100089"},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/01/85/main.PMC8718667.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39891922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic and toxicological analysis of the venom of Micrurus yatesi and its neutralization by an antivenom","authors":"Gianni Mena ,&nbsp;Stephanie Chaves-Araya ,&nbsp;Johelen Chacón ,&nbsp;Enikő Török ,&nbsp;Ferenc Török ,&nbsp;Fabián Bonilla ,&nbsp;Mahmood Sasa ,&nbsp;José María Gutiérrez ,&nbsp;Bruno Lomonte ,&nbsp;Julián Fernández","doi":"10.1016/j.toxcx.2022.100097","DOIUrl":"10.1016/j.toxcx.2022.100097","url":null,"abstract":"<div><p>Coralsnakes belong to the family Elapidae and possess venoms which are lethal to humans and can be grouped based on the predominance of either three finger toxins (3FTxs) or phospholipases A₂ (PLA₂s). A proteomic and toxicological analysis of the venom of the coralsnake <em>Micrurus yatesi</em> was performed. This species, distributed in southeastern Costa Rica, was formerly considered a subspecies of <em>M. alleni</em>. Results showed that this venom is PLA₂-rich, in contrast with the previously studied venom of <em>Micrurus alleni</em>. Toxicological evaluation of the venom, in accordance with proteomic data, revealed that it has a markedly higher <em>in vitro</em> PLA₂ activity upon a synthetic substrate than M. <em>alleni.</em> The evaluation of <em>in vivo</em> myotoxicity in CD-1 mice using histological evaluation and plasma creatine kinase release also showed that <em>M. yatesi</em> venom caused muscle damage. A commercial equine antivenom prepared using the venom of <em>Micrurus nigrocinctus</em> displayed a similar recognition of the venoms of <em>M. yatesi</em> and <em>M. nigrocinctus</em> by enzyme immunoassay<em>.</em> This antivenom also immunorecognized the main fractions of the venom of <em>M. yatesi</em> and was able to neutralize its lethal effect in a murine model.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"13 ","pages":"Article 100097"},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171022000078/pdfft?md5=d8f7513dd9a61f46cdd2b5eae98b0e01&pid=1-s2.0-S2590171022000078-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41496564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}