Pub Date : 2024-01-04DOI: 10.1016/j.toxcx.2023.100183
Aarón Gómez, Andrés Sánchez, Gina Durán, Mauren Villalta, Álvaro Segura, Mariángela Vargas, María Herrera, Melvin Sánchez, José María Gutiérrez, Guillermo León
Snakebite envenomation is a neglected tropical disease posing a high toll of mortality and morbidity in sub-Saharan Africa. Polyspecific antivenoms of broad effectiveness and specially designed for this region require a detailed understanding of the immunological features of the mamba snake (Dendroaspis spp.) venoms for the selection of the most appropriate antigen combination to produce antivenoms of wide neutralizing scope. Monospecific antisera were generated in rabbits against the venoms of the four species of mambas. The toxic effects of the immunization scheme in the animals were evaluated, antibody titers were estimated using immunochemical assays, and neutralization of lethal activity was assessed. By the end of the immunization schedule, rabbits showed normal values of the majority of hematological parameters tested. No muscle tissue damage was noticed, and no alterations in most serum chemical parameters were observed. Immunological analyses revealed a variable extent of cross-reactivity of the monospecific antisera against the heterologous venoms. The venoms of D. jamesoni and D. viridis generated the antisera with broader cross-reactivity by immunochemical parameters. The venoms of D. polylepis and D. viridis generated the antisera with better cross-neutralization of lethality, although the neutralizing ability of all antisera was lower than 0.16 mg venom/mL antiserum against either homologous or heterologous venoms. These experimental results must be scaled to large animal models used in antivenom manufacture at industrial level to assess whether these predictions are reproducible.
蛇咬伤是一种被忽视的热带疾病,在撒哈拉以南非洲地区造成了很高的死亡率和发病率。专门为该地区设计的具有广泛效力的多特异性抗蛇毒血清需要详细了解曼巴蛇(Dendroaspis spp.)毒液的免疫学特征,以便选择最合适的抗原组合来生产具有广泛中和作用的抗蛇毒血清。在兔子身上产生了针对四种曼巴蛇毒液的单特异性抗血清。评估了免疫计划对动物的毒性影响,使用免疫化学测定法估算了抗体滴度,并评估了致死活性的中和作用。免疫计划结束时,兔子的大部分血液学指标都显示正常。未发现肌肉组织损伤,大多数血清化学参数也未发生变化。免疫学分析表明,单特异性抗血清对异种毒液的交叉反应程度不一。从免疫化学参数来看,詹姆逊蝶(D. jamesoni)和蝶形花蝶(D. viridis)的毒液产生的抗血清具有更广泛的交叉反应性。尽管所有抗血清对同源毒液或异源毒液的中和能力都低于 0.16 毫克毒液/毫升抗血清,但 D. polylepis 和 D. viridis 的毒液产生的抗血清具有更好的交叉中和致死性。这些实验结果必须扩大到工业化生产抗蛇毒血清时使用的大型动物模型,以评估这些预测是否具有可重复性。
{"title":"Intrageneric cross-reactivity of monospecific rabbit antisera against venoms of mamba (Elapidae: Dendroaspis spp.) snakes","authors":"Aarón Gómez, Andrés Sánchez, Gina Durán, Mauren Villalta, Álvaro Segura, Mariángela Vargas, María Herrera, Melvin Sánchez, José María Gutiérrez, Guillermo León","doi":"10.1016/j.toxcx.2023.100183","DOIUrl":"https://doi.org/10.1016/j.toxcx.2023.100183","url":null,"abstract":"<div><p>Snakebite envenomation is a neglected tropical disease posing a high toll of mortality and morbidity in sub-Saharan Africa. Polyspecific antivenoms of broad effectiveness and specially designed for this region require a detailed understanding of the immunological features of the mamba snake (<em>Dendroaspis</em> spp.) venoms for the selection of the most appropriate antigen combination to produce antivenoms of wide neutralizing scope. Monospecific antisera were generated in rabbits against the venoms of the four species of mambas. The toxic effects of the immunization scheme in the animals were evaluated, antibody titers were estimated using immunochemical assays, and neutralization of lethal activity was assessed. By the end of the immunization schedule, rabbits showed normal values of the majority of hematological parameters tested. No muscle tissue damage was noticed, and no alterations in most serum chemical parameters were observed. Immunological analyses revealed a variable extent of cross-reactivity of the monospecific antisera against the heterologous venoms. The venoms of <em>D. jamesoni</em> and <em>D. viridis</em> generated the antisera with broader cross-reactivity by immunochemical parameters. The venoms of <em>D. polylepis</em> and <em>D. viridis</em> generated the antisera with better cross-neutralization of lethality, although the neutralizing ability of all antisera was lower than 0.16 mg venom/mL antiserum against either homologous or heterologous venoms. These experimental results must be scaled to large animal models used in antivenom manufacture at industrial level to assess whether these predictions are reproducible.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"21 ","pages":"Article 100183"},"PeriodicalIF":0.0,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171023000358/pdfft?md5=48c19a83c02fe7e56566189241acd1e4&pid=1-s2.0-S2590171023000358-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139108887","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}
Pub Date : 2023-12-30DOI: 10.1016/j.toxcx.2023.100181
Emilio Peruzzi Sancio , Chris Alice Kratzer , John C. Carlson
Background
The venom of Megalopygidae caterpillars causes inflammation and pain. Understanding geographic and temporal variation in exposure will help physicians and the public understand when and where the species in this family may be encountered.
Methods
Photographs uploaded by community scientists to the iNaturalist database were reviewed and identified. GIS data points were used to model distribution of species based on geographic variables at the location of photographs for each group. Data on temporal abundance was also noted.
Results
Maps were created predicting the geographic range for 11 species of Megalopygidae. Peak larval abundance for the most abundant species, Megalopyge opercularis, was determined as September in the southeastern United States and October in south-central US.
Conclusion
Geographic and temporal distributions, based on community science observations, allow for more accurate predictions on the likelihood of encountering venomous Megalopygidae caterpillars.
{"title":"Geographical and temporal distribution of Megalopygidae in the United States and Puerto Rico","authors":"Emilio Peruzzi Sancio , Chris Alice Kratzer , John C. Carlson","doi":"10.1016/j.toxcx.2023.100181","DOIUrl":"https://doi.org/10.1016/j.toxcx.2023.100181","url":null,"abstract":"<div><h3>Background</h3><p>The venom of Megalopygidae caterpillars causes inflammation and pain. Understanding geographic and temporal variation in exposure will help physicians and the public understand when and where the species in this family may be encountered.</p></div><div><h3>Methods</h3><p>Photographs uploaded by community scientists to the iNaturalist database were reviewed and identified. GIS data points were used to model distribution of species based on geographic variables at the location of photographs for each group. Data on temporal abundance was also noted.</p></div><div><h3>Results</h3><p>Maps were created predicting the geographic range for 11 species of Megalopygidae. Peak larval abundance for the most abundant species, <em>Megalopyge opercularis</em>, was determined as September in the southeastern United States and October in south-central US.</p></div><div><h3>Conclusion</h3><p>Geographic and temporal distributions, based on community science observations, allow for more accurate predictions on the likelihood of encountering venomous Megalopygidae caterpillars.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"21 ","pages":"Article 100181"},"PeriodicalIF":0.0,"publicationDate":"2023-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171023000334/pdfft?md5=d44c65c2bbf9e0b44af729b0bd5bb1fe&pid=1-s2.0-S2590171023000334-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139108886","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}
Pub Date : 2023-12-29DOI: 10.1016/j.toxcx.2023.100182
Joel Ramanan da Cruz , Philippe Bulet , Cléria Mendonça de Moraes PhD
The Amazon biome is home to many scorpion species, with around two hundred identified in the region. Of these, forty-eight species have been reported in Brazil so far and six of them are of medical importance: Tityus apiacas, T. metuendus, T. obscurus, T. raquelae, T. silvestris, and T. strandi. Three non-medically important species have also been studied: Opisthanthuscayaporum, Brotheas amazonicus and Rhopalurus laticauda. The venom of the scorpion T. obscurus is the most studied, followed by O. cayaporum. We aim to update the study of these Amazonian scorpion species. We will explore the harmful and beneficial properties of scorpion venom toxins and how they could be applied in drug development. This systematic review will focus on collecting and analyzing venoms from scorpions in Brazil. Only papers on Amazonian scorpion venom studies published between 2001 and 2021 (scientific articles, theses, and dissertations) were selected, based on the lists of scorpions available in the literature. Species found in the Amazon but not confirmed to be Brazilian were omitted from the review. Theses and dissertations were chosen over their derived articles. We found 42 eligible studies (13 theses, 27 articles and 2 patents) out of 17,950 studies and a basic statistical analysis was performed. The literature showed that T. obscurus was the most studied venom with 28 publications, followed by O. cayaporum with seven articles, B. amazonicus with four articles, T. metuendus with two article and R. laticauda with one article. No publication on the characterization of T. silvestris and T. apiacas venoms were found during the reviewed period, only the clinical aspects were covered. There is still much to be explored despite the increasing number of studies conducted in recent years. Amazonian scorpions have promising potential for pharmaceutical and clinical applications.
亚马逊生物群落是许多蝎子物种的家园,该地区已发现约 200 种蝎子。迄今为止,巴西已报告了其中的 48 个物种,其中 6 个物种具有重要的医学价值:Tityus apiacas、T. metuendus、T. obscurus、T. raquelae、T. silvestris 和 T. strandi。还研究了三个非药用物种:Opisthanthus cayaporum、Brotheas amazonicus 和 Rhopalurus laticauda。对蝎子 T. obscurus 的毒液研究最多,其次是 O. cayaporum。我们旨在更新对这些亚马逊蝎子物种的研究。我们将探讨蝎毒毒素的有害和有益特性,以及如何将其应用于药物开发。本系统综述将重点关注巴西蝎子毒液的收集和分析。根据文献中的蝎子清单,仅选取 2001 年至 2021 年间发表的有关亚马逊蝎毒研究的论文(科学文章、论文和学位论文)。在亚马逊发现但未确认为巴西蝎子的物种未列入审查范围。论文和学位论文被选中,而不是其衍生文章。我们从 17950 项研究中找到了 42 项符合条件的研究(13 篇论文、27 篇文章和 2 项专利),并进行了基本的统计分析。文献显示,T. obscurus是研究最多的毒液,共发表了28篇文章,其次是O. cayaporum,共发表了7篇文章,B. amazonicus,共发表了4篇文章,T. metuendus,共发表了2篇文章,R. laticauda,共发表了1篇文章。在审查期间,没有发现关于 T. silvestris 和 T. apiacas 毒液特征的出版物,只涉及临床方面。尽管近年来进行了越来越多的研究,但仍有许多问题有待探索。亚马逊蝎子在制药和临床应用方面具有很大的潜力。
{"title":"Exploring the potential of Brazilian Amazonian scorpion venoms: A comprehensive review of research from 2001 to 2021","authors":"Joel Ramanan da Cruz , Philippe Bulet , Cléria Mendonça de Moraes PhD","doi":"10.1016/j.toxcx.2023.100182","DOIUrl":"10.1016/j.toxcx.2023.100182","url":null,"abstract":"<div><p>The Amazon biome is home to many scorpion species, with around two hundred identified in the region. Of these, forty-eight species have been reported in Brazil so far and six of them are of medical importance: <em>Tityus apiacas, T. metuendus, T. obscurus, T. raquelae, T. silvestris</em>, and T<em>. strandi</em>. Three non-medically important species have also been studied: <em>Opisthanthus</em> <em>cayaporum</em>, <em>Brotheas amazonicus</em> and <em>Rhopalurus laticauda</em>. The venom of the scorpion <em>T. obscurus</em> is the most studied, followed by <em>O. cayaporum</em>. We aim to update the study of these Amazonian scorpion species. We will explore the harmful and beneficial properties of scorpion venom toxins and how they could be applied in drug development. This systematic review will focus on collecting and analyzing venoms from scorpions in Brazil. Only papers on Amazonian scorpion venom studies published between 2001 and 2021 (scientific articles, theses, and dissertations) were selected, based on the lists of scorpions available in the literature. Species found in the Amazon but not confirmed to be Brazilian were omitted from the review. Theses and dissertations were chosen over their derived articles. We found 42 eligible studies (13 theses, 27 articles and 2 patents) out of 17,950 studies and a basic statistical analysis was performed. The literature showed that <em>T. obscurus</em> was the most studied venom with 28 publications, followed by <em>O. cayaporum</em> with seven articles, <em>B. amazonicus</em> with four articles, <em>T. metuendus</em> with two article and <em>R. laticauda</em> with one article. No publication on the characterization of <em>T. silvestris</em> and <em>T. apiacas</em> venoms were found during the reviewed period, only the clinical aspects were covered. There is still much to be explored despite the increasing number of studies conducted in recent years. Amazonian scorpions have promising potential for pharmaceutical and clinical applications.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"21 ","pages":"Article 100182"},"PeriodicalIF":0.0,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171023000346/pdfft?md5=fa68806b6b8be5d6593299f0ec11a4dc&pid=1-s2.0-S2590171023000346-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139193725","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}
Pub Date : 2023-12-07DOI: 10.1016/j.toxcx.2023.100180
Emelyn Salazar , Abcde Cirilo , Armando Reyes , Martha Barrientos , Jacob Galan , Elda E. Sánchez , Montamas Suntravat
Snake venoms contain various molecules known for activating innate immunity and causing local effects associated with increased vascular permeability, such as vascular leakage and edema, common symptoms seen in snakebite envenomings. We have demonstrated that snake venom cysteine-rich secretory proteins (svCRiSPs) from North American pit vipers increase vascular permeability. This study aimed to explore the functional role of CRiSP isolated from Mojave rattlesnake (Crotalus scutulatus scutulatus) venom (Css-CRiSP) on the activation of inflammatory responses in different models. We measured the release of inflammatory mediators in cultured human dermal blood endothelial cells (HDBEC), lymphatic endothelial cells (HDLEC) and monocyte-derived macrophages (MDM) at 0.5, 1, 3, 6, and 24 h after treatment with Css-CRiSP (1 μM). We also determined the acute inflammatory response in BALB/c mice 30 min after intraperitoneal injection of the toxin (2 μg/mouse). Css-CRiSP induced the production of IL-8 and IL-6, but not TNF-α, in HDBEC and HDLEC in a time-dependent manner. In addition, Css-CRiSP significantly enhanced the production of IL-6, TNF-α, IL-8, and IL-1β in MDM. Moreover, it caused a remarkable increase of chemotactic mediators in the exudates of experimental mice. Our results reveal that Css-CRiSPs can promote a sustained release of inflammatory mediators on cell lines and an acute activation of innate immunity in a murine model. These findings contribute to the growing body of evidence supporting the involvement of svCRiSPs in the augmentation of envenomation effects, specifically, the role of svCRiSPs in inducing vascular dysfunction, initiating early inflammatory responses, and facilitating the activation of leukocytes and releasing mediators. These findings will lead to a better understanding of the pathophysiology of envenoming by Mojave rattlesnakes, allowing the development of more efficient therapeutic strategies.
{"title":"Snake venom cysteine-rich secretory protein from Mojave rattlesnake venom (Css-CRiSP) induces acute inflammatory responses on different experimental models","authors":"Emelyn Salazar , Abcde Cirilo , Armando Reyes , Martha Barrientos , Jacob Galan , Elda E. Sánchez , Montamas Suntravat","doi":"10.1016/j.toxcx.2023.100180","DOIUrl":"https://doi.org/10.1016/j.toxcx.2023.100180","url":null,"abstract":"<div><p>Snake venoms contain various molecules known for activating innate immunity and causing local effects associated with increased vascular permeability, such as vascular leakage and edema, common symptoms seen in snakebite envenomings. We have demonstrated that snake venom cysteine-rich secretory proteins (svCRiSPs) from North American pit vipers increase vascular permeability. This study aimed to explore the functional role of CRiSP isolated from Mojave rattlesnake (<em>Crotalus scutulatus scutulatus</em>) venom (Css-CRiSP) on the activation of inflammatory responses in different models. We measured the release of inflammatory mediators in cultured human dermal blood endothelial cells (HDBEC), lymphatic endothelial cells (HDLEC) and monocyte-derived macrophages (MDM) at 0.5, 1, 3, 6, and 24 h after treatment with Css-CRiSP (1 μM). We also determined the acute inflammatory response in BALB/c mice 30 min after intraperitoneal injection of the toxin (2 μg/mouse). Css-CRiSP induced the production of IL-8 and IL-6, but not TNF-α, in HDBEC and HDLEC in a time-dependent manner. In addition, Css-CRiSP significantly enhanced the production of IL-6, TNF-α, IL-8, and IL-1β in MDM. Moreover, it caused a remarkable increase of chemotactic mediators in the exudates of experimental mice. Our results reveal that Css-CRiSPs can promote a sustained release of inflammatory mediators on cell lines and an acute activation of innate immunity in a murine model. These findings contribute to the growing body of evidence supporting the involvement of svCRiSPs in the augmentation of envenomation effects, specifically, the role of svCRiSPs in inducing vascular dysfunction, initiating early inflammatory responses, and facilitating the activation of leukocytes and releasing mediators. These findings will lead to a better understanding of the pathophysiology of envenoming by Mojave rattlesnakes, allowing the development of more efficient therapeutic strategies.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"21 ","pages":"Article 100180"},"PeriodicalIF":0.0,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171023000322/pdfft?md5=2996a61efc3449d9d3d3a67739741ee1&pid=1-s2.0-S2590171023000322-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138559001","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}
Pub Date : 2023-12-01DOI: 10.1016/j.toxcx.2023.100179
Neil R. Balchan , Cara F. Smith , Stephen P. Mackessy
Predation has the potential to impart strong selective pressures on organisms within their environments, resulting in adaptive changes in prey that minimize risk of predation. Pressures from venomous snakes present an exceptional challenge to prey, as venom represents a unique chemical arsenal evolutionarily tailored to incapacitate prey. In response, venom resistance has been detected in various snake prey species, and to varying degrees. This study analyzes venom resistance in an eastern Colorado grassland habitat, where the Prairie Rattlesnake (Crotalus viridis) and Desert Massasauga Rattlesnake (Sistrurus tergeminus edwardsii) co-occur with a suite of grassland rodents. We test for venom resistance across rodent and snake pairings using two geographically distant field sites to determine the role of 1) predation pressure and trophic ecology, and 2) sympatric and allopatric patterns of venom resistance. Resistance was measured using serum-based metalloproteinase inhibition assays to determine potential inhibition of proteolytic activity, augmented by median lethal dose (LD50) assays on rodent species to assess toxicity of crude venoms. Resistance is present in several rodent species, with strong resistance present in populations of Eastern Woodrat (Neotoma floridana), Ord's Kangaroo Rat (Dipodomys ordii), and Northern Grasshopper Mouse (Onychomys leucogaster). Resistance is less developed in other species, including the House Mouse (Mus musculus) and Plains Pocket Mouse (Perognathus flavescens). An unexpected differential is present, where Lincoln County Kangaroo Rats are highly resistant to venom of co-occurring Prairie Rattlesnakes yet are sensitive to an allopatric population of Prairie Rattlesnakes in Weld County. Lincoln Co. Northern Grasshopper Mice also demonstrate extremely elevated resistance to Weld Co. Prairie Rattlesnake venoms, and they may possess resistance mechanisms for myotoxin a, an abundant component of Weld Co. C. v viridis venoms. This study illustrates the complexity of venom resistance in biological communities that can exist when incorporating multiple species interactions. Future studies aimed at characterizing resistance mechanisms at the molecular level will provide a more detailed physiological context for understanding mechanisms by which resistance to venoms occurs.
{"title":"A plethora of rodents: Rattlesnake predators generate unanticipated patterns of venom resistance in a grassland ecosystem","authors":"Neil R. Balchan , Cara F. Smith , Stephen P. Mackessy","doi":"10.1016/j.toxcx.2023.100179","DOIUrl":"https://doi.org/10.1016/j.toxcx.2023.100179","url":null,"abstract":"<div><p>Predation has the potential to impart strong selective pressures on organisms within their environments, resulting in adaptive changes in prey that minimize risk of predation. Pressures from venomous snakes present an exceptional challenge to prey, as venom represents a unique chemical arsenal evolutionarily tailored to incapacitate prey. In response, venom resistance has been detected in various snake prey species, and to varying degrees. This study analyzes venom resistance in an eastern Colorado grassland habitat, where the Prairie Rattlesnake (<em>Crotalus viridis</em>) and Desert Massasauga Rattlesnake (<em>Sistrurus tergeminus edwardsii</em>) co-occur with a suite of grassland rodents. We test for venom resistance across rodent and snake pairings using two geographically distant field sites to determine the role of 1) predation pressure and trophic ecology, and 2) sympatric and allopatric patterns of venom resistance. Resistance was measured using serum-based metalloproteinase inhibition assays to determine potential inhibition of proteolytic activity, augmented by median lethal dose (LD<sub>50</sub>) assays on rodent species to assess toxicity of crude venoms. Resistance is present in several rodent species, with strong resistance present in populations of Eastern Woodrat (<em>Neotoma floridana</em>), Ord's Kangaroo Rat (<em>Dipodomys ordii</em>), and Northern Grasshopper Mouse (<em>Onychomys leucogaster</em>). Resistance is less developed in other species, including the House Mouse (<em>Mus musculus</em>) and Plains Pocket Mouse (<em>Perognathus flavescens</em>). An unexpected differential is present, where Lincoln County Kangaroo Rats are highly resistant to venom of co-occurring Prairie Rattlesnakes yet are sensitive to an allopatric population of Prairie Rattlesnakes in Weld County. Lincoln Co. Northern Grasshopper Mice also demonstrate extremely elevated resistance to Weld Co. Prairie Rattlesnake venoms, and they may possess resistance mechanisms for myotoxin a, an abundant component of Weld Co. <em>C. v viridis</em> venoms. This study illustrates the complexity of venom resistance in biological communities that can exist when incorporating multiple species interactions. Future studies aimed at characterizing resistance mechanisms at the molecular level will provide a more detailed physiological context for understanding mechanisms by which resistance to venoms occurs.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"21 ","pages":"Article 100179"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171023000310/pdfft?md5=12a7fb810b26ed79386c802f246b66f8&pid=1-s2.0-S2590171023000310-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138483871","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}
Pub Date : 2023-11-10DOI: 10.1016/j.toxcx.2023.100171
Spencer Greene , Matthew Gilbert , Brian Wolk , Sharan Campleman , Anne-Michelle Ruha , on behalf of the ToxIC Snakebite Study Group
The geographic variation of Mohave rattlesnake (Crotalus scutulatus) venom is well established. We reviewed all the Mohave rattlesnake bites reported to the Toxicology Investigators Consortium's North American Snakebite Registry between January 1, 2015 and 12/31/2021. Data reviewed for this study included details regarding the snake encounter, patient demographics, signs and symptoms, treatment, and outcomes. Our objective was to describe the epidemiology, clinical manifestations, and management of Mohave rattlesnake envenomations using prospective data from two geographically distinct sites. There were 20 subjects, including eight nonpregnant females. Ages ranged from seven to 75 years, median age 48. Nine of the bites were managed in Arizona and 11 in California. In Arizona, all envenomated patients had local swelling. None had neurological toxicity. In California, swelling was present in nine patients. Neurological effects were observed in five subjects. Four Arizona patients and one California patient had hypotension requiring treatment. Each site had one patient with thrombocytopenia. An Arizona patient who sustained a bite to the face was intubated. Rhabdomyolysis occurred in two California patients. All envenomated patients received antivenom. Mohave rattlesnakes have the potential to cause significant local and/or systemic toxicity. Neurotoxicity was not observed in envenomations from Mohave rattlesnakes that presumably lack Mohave toxin, but hypotension and gastrointestinal signs were more common than in bites from snakes believed to possess Mohave toxin. Neurological toxicity was limited to paresthesias and fasciculations. Significant skeletal or respiratory muscle weakness was not observed in our study population.
{"title":"Geographic variation in the clinical features of Mohave rattlesnake (Crotalus scutulatus) envenomations reported to the North American Snakebite Registry","authors":"Spencer Greene , Matthew Gilbert , Brian Wolk , Sharan Campleman , Anne-Michelle Ruha , on behalf of the ToxIC Snakebite Study Group","doi":"10.1016/j.toxcx.2023.100171","DOIUrl":"10.1016/j.toxcx.2023.100171","url":null,"abstract":"<div><p>The geographic variation of Mohave rattlesnake (<em>Crotalus scutulatus</em>) venom is well established. We reviewed all the Mohave rattlesnake bites reported to the Toxicology Investigators Consortium's North American Snakebite Registry between January 1, 2015 and 12/31/2021. Data reviewed for this study included details regarding the snake encounter, patient demographics, signs and symptoms, treatment, and outcomes. Our objective was to describe the epidemiology, clinical manifestations, and management of Mohave rattlesnake envenomations using prospective data from two geographically distinct sites. There were 20 subjects, including eight nonpregnant females. Ages ranged from seven to 75 years, median age 48. Nine of the bites were managed in Arizona and 11 in California. In Arizona, all envenomated patients had local swelling. None had neurological toxicity. In California, swelling was present in nine patients. Neurological effects were observed in five subjects. Four Arizona patients and one California patient had hypotension requiring treatment. Each site had one patient with thrombocytopenia. An Arizona patient who sustained a bite to the face was intubated. Rhabdomyolysis occurred in two California patients. All envenomated patients received antivenom. Mohave rattlesnakes have the potential to cause significant local and/or systemic toxicity. Neurotoxicity was not observed in envenomations from Mohave rattlesnakes that presumably lack Mohave toxin, but hypotension and gastrointestinal signs were more common than in bites from snakes believed to possess Mohave toxin. Neurological toxicity was limited to paresthesias and fasciculations. Significant skeletal or respiratory muscle weakness was not observed in our study population.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"21 ","pages":"Article 100171"},"PeriodicalIF":0.0,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171023000231/pdfft?md5=a8133692af30c022c247dd874ae3f932&pid=1-s2.0-S2590171023000231-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135614451","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}
Jellyfish envenomation is a common marine injury. We report a case of a 9-year-old boy who developed muscle weakness and rhabdomyolysis after a jellyfish sting. He was stung on the face, hands, and feet. He sustained immediate pain and numbness; however no immediate action was taken. He was taken to a primary health clinic and discharged with syrup Paracetamol 15mg/kg/dose and syrup Chlorpheniramine maleate 0.1mg/kg/dose for symptomatic relief. Over the next several days, the pain became generalized involving upper and lower limbs, aggravated by movement, and not alleviated by analgesia nor antihistamine. His condition worsened with the development of weakness of upper and lower limbs and ‘tea-colored’ urine from day 3 of illness. He received treatment for rhabdomyolysis at a district hospital. Maintaining hydration and urine output and symptomatic relief are central to treatment. His muscle pain and weakness improved. He was discharged well and remained asymptomatic at follow up.
{"title":"Rhabdomyolysis due to unidentified jellyfish envenomation in west Malaysian waters","authors":"Jia Shyi Loy , Chyi Chyi Khoo , Tilagavahti Arumugam , Geok Hoon Ngian , Ahmad Khaldun Ismail","doi":"10.1016/j.toxcx.2023.100170","DOIUrl":"https://doi.org/10.1016/j.toxcx.2023.100170","url":null,"abstract":"<div><p>Jellyfish envenomation is a common marine injury. We report a case of a 9-year-old boy who developed muscle weakness and rhabdomyolysis after a jellyfish sting. He was stung on the face, hands, and feet. He sustained immediate pain and numbness; however no immediate action was taken. He was taken to a primary health clinic and discharged with syrup Paracetamol 15mg/kg/dose and syrup Chlorpheniramine maleate 0.1mg/kg/dose for symptomatic relief. Over the next several days, the pain became generalized involving upper and lower limbs, aggravated by movement, and not alleviated by analgesia nor antihistamine. His condition worsened with the development of weakness of upper and lower limbs and ‘tea-colored’ urine from day 3 of illness. He received treatment for rhabdomyolysis at a district hospital. Maintaining hydration and urine output and symptomatic relief are central to treatment. His muscle pain and weakness improved. He was discharged well and remained asymptomatic at follow up.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"21 ","pages":"Article 100170"},"PeriodicalIF":0.0,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71728446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1016/j.toxcx.2023.100166
Sarah K.D. Pease , Todd A. Egerton , Kimberly S. Reece , Marta P. Sanderson , Michelle D. Onofrio , Evan Yeargan , Adam Wood , Amanda Roach , I-Shuo Wade Huang , Gail P. Scott , Allen R. Place , Amy M. Hayes , Juliette L. Smith
Oysters (Crassostrea virginica) were screened for 12 phycotoxins over two years in nearshore waters to collect baseline phycotoxin data and to determine prevalence of phycotoxin co-occurrence in the commercially and ecologically-relevant species. Trace to low concentrations of azaspiracid-1 and -2 (AZA1, AZA2), domoic acid (DA), okadaic acid (OA), and dinophysistoxin-1 (DTX1) were detected, orders of magnitude below seafood safety action levels. Microcystins (MCs), MC-RR and MC-YR, were also found in oysters (maximum: 7.12 μg MC-RR/kg shellfish meat wet weight), warranting consideration of developing action levels for freshwater phycotoxins in marine shellfish. Oysters contained phycotoxins that impair shellfish health: karlotoxin1-1 and 1–3 (KmTx1-1, KmTx1-3), goniodomin A (GDA), and pectenotoxin-2 (PTX2). Co-occurrence of phycotoxins in oysters was common (54%, n = 81). AZAs and DA co-occurred most frequently of the phycotoxins investigated that are a concern for human health (n = 13) and PTX2 and KmTxs co-occurred most frequently amongst the phycotoxins of concern for shellfish health (n = 9). Various harmful algal bloom (HAB) monitoring methods and tools were assessed for their effectiveness at indicating levels of phycotoxins in oysters. These included co-deployed solid phase adsorption toxin tracking (SPATT) devices, toxin levels in particulate organic matter (POM, >1.5 μm) and whole water samples and cell concentrations from water samples as determined by microscopy and quantitative real-time PCR (qPCR). The dominant phycotoxin varied between SPATTs and all other phycotoxin sample types, and out of the 11 phycotoxins detected in oysters, only four and seven were detected in POM and whole water respectively, indicating phycotoxin profile mismatch between ecosystem compartments. Nevertheless, there were correlations between DA in oysters and whole water (simple linear regression [LR]: R2 = 0.6, p < 0.0001, n = 40), and PTX2 in oysters and SPATTs (LR: R2 = 0.3, p = 0.001, n = 36), providing additional monitoring tools for these phycotoxins, but oyster samples remain the best overall indicators of seafood safety.
{"title":"Co-occurrence of marine and freshwater phycotoxins in oysters, and analysis of possible predictors for management","authors":"Sarah K.D. Pease , Todd A. Egerton , Kimberly S. Reece , Marta P. Sanderson , Michelle D. Onofrio , Evan Yeargan , Adam Wood , Amanda Roach , I-Shuo Wade Huang , Gail P. Scott , Allen R. Place , Amy M. Hayes , Juliette L. Smith","doi":"10.1016/j.toxcx.2023.100166","DOIUrl":"10.1016/j.toxcx.2023.100166","url":null,"abstract":"<div><p>Oysters (<em>Crassostrea virginica</em>) were screened for 12 phycotoxins over two years in nearshore waters to collect baseline phycotoxin data and to determine prevalence of phycotoxin co-occurrence in the commercially and ecologically-relevant species. Trace to low concentrations of azaspiracid-1 and -2 (AZA1, AZA2), domoic acid (DA), okadaic acid (OA), and dinophysistoxin-1 (DTX1) were detected, orders of magnitude below seafood safety action levels. Microcystins (MCs), MC-RR and MC-YR, were also found in oysters (maximum: 7.12 μg MC-RR/kg shellfish meat wet weight), warranting consideration of developing action levels for freshwater phycotoxins in marine shellfish. Oysters contained phycotoxins that impair shellfish health: karlotoxin1-1 and 1–3 (KmTx1-1, KmTx1-3), goniodomin A (GDA), and pectenotoxin-2 (PTX2). Co-occurrence of phycotoxins in oysters was common (54%, n = 81). AZAs and DA co-occurred most frequently of the phycotoxins investigated that are a concern for human health (n = 13) and PTX2 and KmTxs co-occurred most frequently amongst the phycotoxins of concern for shellfish health (n = 9). Various harmful algal bloom (HAB) monitoring methods and tools were assessed for their effectiveness at indicating levels of phycotoxins in oysters. These included co-deployed solid phase adsorption toxin tracking (SPATT) devices, toxin levels in particulate organic matter (POM, >1.5 μm) and whole water samples and cell concentrations from water samples as determined by microscopy and quantitative real-time PCR (qPCR). The dominant phycotoxin varied between SPATTs and all other phycotoxin sample types, and out of the 11 phycotoxins detected in oysters, only four and seven were detected in POM and whole water respectively, indicating phycotoxin profile mismatch between ecosystem compartments. Nevertheless, there were correlations between DA in oysters and whole water (simple linear regression [LR]: R<sup>2</sup> = 0.6, p < 0.0001, n = 40), and PTX2 in oysters and SPATTs (LR: R<sup>2</sup> = 0.3, p = 0.001, n = 36), providing additional monitoring tools for these phycotoxins, but oyster samples remain the best overall indicators of seafood safety.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"19 ","pages":"Article 100166"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b3/90/main.PMC10336265.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10180375","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}
Brevetoxins (BTX) are a group of marine neurotoxins produced by the harmful alga Karenia brevis. Numerous studies have shown that BTX are rapidly accumulated and metabolized in shellfish and mammals. However, there are only limited data on BTX metabolism in fish, despite growing evidence that fish serve as vectors for BTX transfer in marine food webs. In this study, we aimed to investigate the in vitro biotransformation of BTX-2, the major constituent of BTX profiles in K. brevis, in several species of northern Gulf of Mexico fish. Metabolism assays were performed using hepatic microsomes prepared in-house as well as commercially available human microsomes for comparison, focusing on phase I reactions mediated by cytochrome P450 monooxygenase (CYP) enzymes. Samples were analyzed by UHPLC-HRMS(/MS) to monitor BTX-2 depletion and characterize BTX metabolites based on MS/MS fragmentation pathways. Our results showed that both fish and human liver microsomes rapidly depleted BTX-2, resulting in a 72–99% reduction within 1 h of incubation. We observed the simultaneous production of 22 metabolites functionalized by reductions, oxidations, and other phase I reactions. We were able to identify the previously described congeners BTX-3 and BTX-B5, and tentatively identified BTX-9, 41,43-dihydro-BTX-2, several A-ring hydrolysis products, as well as several novel metabolites. Our results confirmed that fish are capable of similar BTX biotransformation reactions as reported for shellfish and mammals, but comparison of metabolite formation across the tested species suggested considerable interspecific variation in BTX-2 metabolism potentially leading to divergent BTX profiles. We additionally observed non-enzymatic formation of BTX-2 and BTX-3 glutathione conjugates. Collectively, these findings have important implications for determining the ecotoxicological fate of BTX in marine food webs.
{"title":"Identification and cross-species comparison of in vitro phase I brevetoxin (BTX-2) metabolites in northern Gulf of Mexico fish and human liver microsomes by UHPLC-HRMS(/MS)","authors":"Jessica Kay Gwinn , Alison Robertson , Lada Ivanova , Christiane Kruse Fæste , Fedor Kryuchkov , Silvio Uhlig","doi":"10.1016/j.toxcx.2023.100168","DOIUrl":"https://doi.org/10.1016/j.toxcx.2023.100168","url":null,"abstract":"<div><p>Brevetoxins (BTX) are a group of marine neurotoxins produced by the harmful alga <em>Karenia brevis</em>. Numerous studies have shown that BTX are rapidly accumulated and metabolized in shellfish and mammals. However, there are only limited data on BTX metabolism in fish, despite growing evidence that fish serve as vectors for BTX transfer in marine food webs. In this study, we aimed to investigate the <em>in vitro</em> biotransformation of BTX-2, the major constituent of BTX profiles in <em>K. brevis</em>, in several species of northern Gulf of Mexico fish. Metabolism assays were performed using hepatic microsomes prepared in-house as well as commercially available human microsomes for comparison, focusing on phase I reactions mediated by cytochrome P450 monooxygenase (CYP) enzymes. Samples were analyzed by UHPLC-HRMS(/MS) to monitor BTX-2 depletion and characterize BTX metabolites based on MS/MS fragmentation pathways. Our results showed that both fish and human liver microsomes rapidly depleted BTX-2, resulting in a 72–99% reduction within 1 h of incubation. We observed the simultaneous production of 22 metabolites functionalized by reductions, oxidations, and other phase I reactions. We were able to identify the previously described congeners BTX-3 and BTX-B5, and tentatively identified BTX-9, 41,43-dihydro-BTX-2, several A-ring hydrolysis products, as well as several novel metabolites. Our results confirmed that fish are capable of similar BTX biotransformation reactions as reported for shellfish and mammals, but comparison of metabolite formation across the tested species suggested considerable interspecific variation in BTX-2 metabolism potentially leading to divergent BTX profiles. We additionally observed non-enzymatic formation of BTX-2 and BTX-3 glutathione conjugates. Collectively, these findings have important implications for determining the ecotoxicological fate of BTX in marine food webs.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"19 ","pages":"Article 100168"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50170895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1016/j.toxcx.2023.100159
Enrique de Jesus-López , Luis Cuéllar-Balleza , Luis Fernando Díaz-Peña , Francisco Javier Luna-Vázquez , César Ibarra-Alvarado , José Alejandro García-Arredondo
Tarantula venoms may be a natural source of new vasodilator components useful in pharmacological research. Moreover, biological function data of the venoms are important to enhance the knowledge about the biodiversity and evolution of these species. The present study aims to describe the vasodilatory activity induced by the venom of Poecilotheria ornata on isolated rat aortic rings. This venom induced a vasodilator activity that was significantly reduced after incubation with L-NAME or ODQ. Measurements of nitrite concentrations on rat aorta homogenates showed that the venom significantly increased the basal levels. Moreover, the venom attenuates the contraction induced by calcium. These results suggest that P. ornata venom contains a mixture of vasodilator components that act through the activation of the nitric oxide/cGMP pathway, as well as, through an endothelium-independent mechanism that involves the calcium influx into vascular smooth muscle cells.
{"title":"Vasodilator activity of Poecilotheria ornata venom involves activation of the NO/cGMP pathway and inhibition of calcium influx to vascular smooth muscle cells","authors":"Enrique de Jesus-López , Luis Cuéllar-Balleza , Luis Fernando Díaz-Peña , Francisco Javier Luna-Vázquez , César Ibarra-Alvarado , José Alejandro García-Arredondo","doi":"10.1016/j.toxcx.2023.100159","DOIUrl":"https://doi.org/10.1016/j.toxcx.2023.100159","url":null,"abstract":"<div><p>Tarantula venoms may be a natural source of new vasodilator components useful in pharmacological research. Moreover, biological function data of the venoms are important to enhance the knowledge about the biodiversity and evolution of these species. The present study aims to describe the vasodilatory activity induced by the venom of <em>Poecilotheria ornata</em> on isolated rat aortic rings. This venom induced a vasodilator activity that was significantly reduced after incubation with L-NAME or ODQ. Measurements of nitrite concentrations on rat aorta homogenates showed that the venom significantly increased the basal levels. Moreover, the venom attenuates the contraction induced by calcium. These results suggest that <em>P. ornata</em> venom contains a mixture of vasodilator components that act through the activation of the nitric oxide/cGMP pathway, as well as, through an endothelium-independent mechanism that involves the calcium influx into vascular smooth muscle cells.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"19 ","pages":"Article 100159"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50170894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}