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Intrageneric cross-reactivity of monospecific rabbit antisera against venoms of mamba (Elapidae: Dendroaspis spp.) snakes 针对曼巴蛇(Elapidae: Dendroaspis spp.)
Q2 TOXICOLOGY Pub Date : 2024-01-04 DOI: 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。
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引用次数: 0
Geographical and temporal distribution of Megalopygidae in the United States and Puerto Rico 美国和波多黎各 Megalopygidae 的地理和时间分布情况
Q2 TOXICOLOGY Pub Date : 2023-12-30 DOI: 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.

背景Megalopygidae毛虫的毒液会引起炎症和疼痛。方法对社区科学家上传到 iNaturalist 数据库的照片进行审查和识别。根据每组照片拍摄地点的地理变量,使用 GIS 数据点建立物种分布模型。结果绘制了预测 11 种巨蜥科动物地理分布的地图。最丰富的物种 Megalopyge opercularis 的幼虫丰度高峰期被确定为美国东南部的 9 月和美国中南部的 10 月。
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引用次数: 0
Exploring the potential of Brazilian Amazonian scorpion venoms: A comprehensive review of research from 2001 to 2021 探索巴西亚马逊蝎毒的潜力:2001 年至 2021 年研究综述
Q2 TOXICOLOGY Pub Date : 2023-12-29 DOI: 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: Opisthanthus cayaporum, 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。
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引用次数: 0
Snake venom cysteine-rich secretory protein from Mojave rattlesnake venom (Css-CRiSP) induces acute inflammatory responses on different experimental models 莫哈韦响尾蛇蛇毒富半胱氨酸分泌蛋白(Css-CRiSP)在不同实验模型上诱导急性炎症反应
Q2 TOXICOLOGY Pub Date : 2023-12-07 DOI: 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.

蛇毒含有各种已知的分子,可激活先天性免疫,并引起与血管通透性增加有关的局部效应,如血管渗漏和水肿,这些都是蛇咬伤中常见的症状。我们已经证明,北美蝮蛇的蛇毒富半胱氨酸分泌蛋白(svCRiSPs)会增加血管通透性。本研究旨在探索从莫哈韦响尾蛇(Crotalus scutulatus scutulatus)毒液中分离出的 CRiSP(Css-CRiSP)在不同模型中激活炎症反应的功能作用。我们在 Css-CRiSP(1 μM)处理后 0.5、1、3、6 和 24 小时测定了培养的人真皮血液内皮细胞(HDBEC)、淋巴内皮细胞(HDLEC)和单核细胞衍生巨噬细胞(MDM)中炎症介质的释放。我们还测定了腹腔注射毒素(2 μg/只小鼠)30 分钟后 BALB/c 小鼠的急性炎症反应。Css-CRiSP 以时间依赖性方式诱导 HDBEC 和 HDLEC 产生 IL-8 和 IL-6,但不诱导 TNF-α。此外,Css-CRiSP 还能显著增强 MDM 中 IL-6、TNF-α、IL-8 和 IL-1β 的产生。此外,它还导致实验小鼠渗出液中的趋化介质明显增加。我们的研究结果表明,在小鼠模型中,Css-CRiSPs 可促进细胞系炎症介质的持续释放和先天性免疫的急性激活。越来越多的证据支持 svCRiSPs 参与增强噬毒效应,特别是 svCRiSPs 在诱导血管功能障碍、启动早期炎症反应、促进白细胞活化和释放介质方面的作用,这些研究结果为这些证据做出了贡献。这些发现将有助于更好地了解莫哈韦响尾蛇致病的病理生理学,从而制定更有效的治疗策略。
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引用次数: 0
A plethora of rodents: Rattlesnake predators generate unanticipated patterns of venom resistance in a grassland ecosystem 大量的啮齿动物:响尾蛇捕食者在草原生态系统中产生了意想不到的毒液抗性模式
Q2 TOXICOLOGY Pub Date : 2023-12-01 DOI: 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.

捕食有可能给环境中的生物带来强大的选择压力,导致猎物的适应性变化,从而最大限度地降低被捕食的风险。来自毒蛇的压力对猎物来说是一个特殊的挑战,因为毒液代表了一种独特的化学武器库,进化上专门用来使猎物丧失能力。因此,在不同种类的蛇类猎物中发现了不同程度的毒液抗性。本研究分析了科罗拉多州东部草原栖息地的毒液抗性,在那里,草原响尾蛇(Crotalus viridis)和沙漠马萨索加响尾蛇(Sistrurus tergeminus edwardsii)与一组草原啮齿动物共同生活。我们在两个地理位置较远的野外地点测试了啮齿动物和蛇对毒液的抗性,以确定1)捕食压力和营养生态的作用,以及2)同域和异域模式的毒液抗性。采用基于血清的金属蛋白酶抑制试验来测定其对蛋白水解活性的潜在抑制作用,并通过对啮齿动物的中位致死剂量(LD50)试验来评估粗毒液的毒性。抗性存在于几种啮齿动物中,在东部木鼠(Neotoma florida)、Ord's Kangaroo Rat (Dipodomys ordii)和Northern Grasshopper Mouse (Onychomys leucogaster)种群中存在较强的抗性。在其他物种中,包括家鼠(小家鼠)和平原口袋鼠(Perognathus flavescens),抗性较弱。一个意想不到的差异是存在的,林肯县袋鼠鼠对共同发生的草原响尾蛇的毒液具有高度抗性,但对威尔德县的异域草原响尾蛇种群敏感。林肯公司的北方蚱蜢老鼠对威尔德公司的草原响尾蛇毒液也表现出极高的抗性,它们可能具有对肌肉毒素a的抗性机制,这是威尔德公司c.v病毒毒液的丰富成分。这项研究说明了生物群落中毒液抗性的复杂性,当纳入多物种相互作用时,可能存在。未来旨在分子水平上表征抗性机制的研究将为理解对毒液产生抗性的机制提供更详细的生理背景。
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引用次数: 0
Geographic variation in the clinical features of Mohave rattlesnake (Crotalus scutulatus) envenomations reported to the North American Snakebite Registry 向北美蛇咬伤登记处报告的莫哈维响尾蛇(Crotalus scutulatus)中毒的临床特征的地理变异
Q2 TOXICOLOGY Pub Date : 2023-11-10 DOI: 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.

莫哈维响尾蛇(Crotalus scutulatus)毒液的地理变异已经得到了很好的证实。我们回顾了2015年1月1日至2021年12月31日期间向毒理学调查协会北美蛇咬伤登记处报告的所有莫哈维响尾蛇咬伤。本研究回顾的数据包括与蛇接触的细节、患者人口统计、体征和症状、治疗和结果。我们的目的是描述莫哈维响尾蛇中毒的流行病学、临床表现和管理,使用来自两个地理位置不同的地点的前瞻性数据。共有20名受试者,包括8名未怀孕的女性。年龄从7岁到75岁不等,中位年龄48岁。其中9个在亚利桑那州,11个在加利福尼亚州。在亚利桑那州,所有中毒患者都有局部肿胀。没有一例具有神经毒性。在加州,9名患者出现肿胀。在5名受试者中观察到神经学效应。四名亚利桑那州患者和一名加州患者患有低血压,需要治疗。每个部位有1例血小板减少患者。亚利桑那州的一名患者因面部被咬伤而接受了插管治疗。两名加州患者出现横纹肌溶解。所有中毒患者均接受抗蛇毒血清治疗。莫哈维响尾蛇有可能造成严重的局部和/或全身毒性。在可能缺乏莫哈维毒素的莫哈维响尾蛇的毒液中没有观察到神经毒性,但低血压和胃肠道症状比被认为含有莫哈维毒素的蛇咬伤更常见。神经毒性仅限于感觉异常和束控。在我们的研究人群中没有观察到明显的骨骼肌或呼吸肌无力。
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引用次数: 0
Rhabdomyolysis due to unidentified jellyfish envenomation in west Malaysian waters 西马来西亚水域不明水母中毒导致横纹肌溶解
Q2 TOXICOLOGY Pub Date : 2023-11-02 DOI: 10.1016/j.toxcx.2023.100170
Jia Shyi Loy , Chyi Chyi Khoo , Tilagavahti Arumugam , Geok Hoon Ngian , Ahmad Khaldun Ismail

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.

水母中毒是一种常见的海洋损伤。我们报告了一例9岁男孩在水母蜇伤后出现肌无力和横纹肌溶解症的病例。他的脸、手和脚都被刺痛了。他立即感到疼痛和麻木;但没有立即采取行动。他被送往初级卫生诊所,出院时服用对乙酰氨基酚15mg/kg/剂糖浆和马来酸氯苯那敏0.1mg/kg/剂,以缓解症状。在接下来的几天里,疼痛变得普遍,包括上肢和下肢,因运动而加剧,但镇痛和抗组胺药都没有缓解。从患病第3天起,他的病情随着上下肢无力和“茶色”尿液的发展而恶化。他在一家地区医院接受了横纹肌溶解症的治疗。保持水合作用和尿量以及症状缓解是治疗的核心。他的肌肉疼痛和虚弱有所好转。他出院后情况良好,随访时仍无症状。
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引用次数: 0
Co-occurrence of marine and freshwater phycotoxins in oysters, and analysis of possible predictors for management 牡蛎中海洋和淡水藻毒素的共存,以及可能的管理预测因素分析
Q2 TOXICOLOGY Pub Date : 2023-09-01 DOI: 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.

在近海水域对牡蛎(Crassostrea virginica)进行为期两年的12种藻毒素筛选,以收集基线藻毒素数据,并确定商业和生态相关物种中藻毒素共现的流行率。检测到微量低浓度的氮杂螺旋体酸-1和-2(AZA1、AZA2)、软骨藻酸(DA)、冈田酸(OA)和藻毒素-1(DTX1),比海鲜安全作用水平低几个数量级。在牡蛎中也发现了微囊藻毒素(MCs)、MC-RR和MC-YR(最大值:7.12μg MC-RR/kg贝类肉湿重),值得考虑开发海洋贝类中淡水藻毒素的作用水平。牡蛎中含有损害贝类健康的藻毒素:卡罗毒素1-1和1-3(KmTx1-1,KmTx1-3)、角蛋白A(GDA)和果胶毒素-2(PTX2)。藻毒素在牡蛎中的共存是常见的(54%,n=81)。在关注人类健康的所研究的藻毒素中,AZAs和DA共同出现的频率最高(n=13),而PTX2和KmTxs共同发生的频率最高,是关注贝类健康的藻毒素(n=9)。评估了各种有害藻华(HAB)监测方法和工具在指示牡蛎中藻毒素水平方面的有效性。其中包括共同部署的固相吸附毒素跟踪(SPATT)设备、颗粒有机物(POM,>;1.5μm)和全水样中的毒素水平以及通过显微镜和定量实时PCR(qPCR)测定的水样中的细胞浓度。SPATT和所有其他藻毒素样品类型之间的优势藻毒素各不相同,在牡蛎中检测到的11种藻毒素中,POM和全水中分别只有4种和7种检测到,这表明生态系统区室之间的藻毒素图谱不匹配。然而,牡蛎和淡水中的DA(简单线性回归[LR]:R2=0.6,p<;0.0001,n=40)与牡蛎和SPATT中的PTX2(LR:R2=0.3,p=0.001,n=36)之间存在相关性,为这些藻毒素提供了额外的监测工具,但牡蛎样本仍然是海鲜安全的最佳总体指标。
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引用次数: 1
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) UHPLC-HRMS(/MS)在墨西哥湾北部鱼类和人肝微粒体中体外I期brevetoxin(BTX-2)代谢产物的鉴定和跨物种比较
Q2 TOXICOLOGY Pub Date : 2023-09-01 DOI: 10.1016/j.toxcx.2023.100168
Jessica Kay Gwinn , Alison Robertson , Lada Ivanova , Christiane Kruse Fæste , Fedor Kryuchkov , Silvio Uhlig

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.

Brevetoxins(BTX)是由有害藻类Karenia brevis产生的一组海洋神经毒素。大量研究表明,BTX在贝类和哺乳动物中快速积累和代谢。然而,尽管越来越多的证据表明鱼类是海洋食物网中BTX转移的载体,但关于鱼类BTX代谢的数据有限。在这项研究中,我们旨在研究短鳍金枪鱼BTX图谱的主要成分BTX-2在墨西哥湾北部几种鱼类中的体外生物转化。使用内部制备的肝微粒体和市售的人微粒体进行代谢测定以进行比较,重点是细胞色素P450单加氧酶(CYP)介导的I期反应。通过UHPLC-HRMS(/MS)分析样品,以监测BTX-2的耗竭,并基于MS/MS裂解途径表征BTX代谢产物。我们的研究结果表明,鱼类和人类肝微粒体都迅速耗尽了BTX-2,在孵育1小时内减少了72–99%。我们观察到通过还原、氧化和其他I相反应同时产生22种功能化的代谢物。我们能够鉴定先前描述的同源物BTX-3和BTX-B5,并初步鉴定了BTX-9,41,4-二氢-BTX-2、几种A环水解产物以及几种新的代谢产物。我们的研究结果证实,鱼类能够进行与贝类和哺乳动物类似的BTX生物转化反应,但对测试物种代谢产物形成的比较表明,BTX-2代谢的种间差异很大,可能导致BTX图谱的差异。我们还观察到BTX-2和BTX-3谷胱甘肽缀合物的非酶促形成。总之,这些发现对确定BTX在海洋食物网中的生态毒理学命运具有重要意义。
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引用次数: 0
Vasodilator activity of Poecilotheria ornata venom involves activation of the NO/cGMP pathway and inhibition of calcium influx to vascular smooth muscle cells 珊瑚虫毒液的血管舒张活性包括激活NO/cGMP途径和抑制钙流入血管平滑肌细胞
Q2 TOXICOLOGY Pub Date : 2023-09-01 DOI: 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.

狼蛛毒液可能是药理学研究中有用的新血管舒张剂成分的天然来源。此外,毒液的生物功能数据对于增强对这些物种的生物多样性和进化的了解非常重要。本研究旨在描述蛇床子毒液对离体大鼠主动脉环的血管舒张活性。这种毒液诱导的血管舒张活性在与L-NAME或ODQ孵育后显著降低。对大鼠主动脉匀浆中亚硝酸盐浓度的测量表明,毒液显著提高了基础水平。此外,毒液可以减弱钙引起的收缩。这些结果表明,P.ornata毒液含有血管舒张剂成分的混合物,这些成分通过激活一氧化氮/cGMP途径以及通过涉及钙流入血管平滑肌细胞的内皮非依赖性机制发挥作用。
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引用次数: 0
期刊
Toxicon: X
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