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Erratum to “The influence of ecological factors on cnidarian venoms” [Toxicon: X 9–10C (2021) 100067] 《生态因子对刺胞动物毒液的影响》的勘误[毒物学:X 9-10C (2021) 100067]
Q2 TOXICOLOGY Pub Date : 2022-09-01 DOI: 10.1016/j.toxcx.2022.100134
E.P. O'Hara, D. Wilson, J.E. Seymour
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引用次数: 0
Preclinical efficacy testing of three antivenoms against Naja ashei venom-induced lethality 三种抗眼镜蛇毒素致人死亡的临床前疗效测试
Q2 TOXICOLOGY Pub Date : 2022-06-01 DOI: 10.1016/j.toxcx.2022.100124
Mitchel Otieno Okumu , James Mucunu Mbaria , Joseph Kangangi Gikunju , Paul Gichohi Mbuthia , Vincent Odongo Madadi , Francis Okumu Ochola , Kenneth Narotso Maloba , Joseph Gichuki Nderitu

This study aimed to determine the efficacy of Inoserp, Vins bioproducts, and South African Institute of Medical Research (SAIMR) polyvalent antivenoms in neutralizing Naja ashei venom-induced lethality in mice. The neutralization efficacy of the antivenoms were expressed as effective dose, median effective ratio, potency, normalized potency, volume, and the number of vials of antivenom required to neutralize 100 mg of Naja ashei venom (NAV).

本研究旨在确定Inoserp、Vins生物制品和南非医学研究所(SAIMR)多价抗蛇毒血清在中和Naja ashei毒液致小鼠死亡中的功效。用有效剂量、中位有效比、效价、归一化效价、体积和中和100 mg NAV所需的抗蛇毒血清瓶数来表示抗蛇毒血清的中和效果。
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引用次数: 1
The myth of cobra venom cytotoxin: More than just direct cytolytic actions 眼镜蛇毒液细胞毒素的神话:不仅仅是直接的细胞溶解作用
Q2 TOXICOLOGY Pub Date : 2022-06-01 DOI: 10.1016/j.toxcx.2022.100123
Jia Jin Hiu , Michelle Khai Khun Yap

Cobra venom cytotoxin (CTX) is a non-enzymatic three-finger toxin that constitutes 40–60% of cobra venom. Thus, it plays an important role in the pathophysiology of cobra envenomation, especially in local dermonecrosis. The three-finger hydrophobic loops of CTX determine the cytotoxicity. Nevertheless, the actual mechanisms of cytotoxicity are not fully elucidated as they involve not only cytolytic actions but also intracellular signalling-mediated cell death pathways. Furthermore, the possible transition cell death pattern remains to be explored. The actual molecular mechanisms require further studies to unveil the relationship between different CTXs from different cobra species and cell types which may result in differential cell death patterns. Here, we discuss the biophysical interaction of CTX with the cell membrane involving four binding modes: electrostatic interaction, hydrophobic partitioning, isotropic phase, and oligomerisation. Oligomerisation of CTX causes pore formation in the membrane lipid bilayer. Additionally, the CTX-induced apoptotic pathway can be executed via death receptor-mediated extrinsic pathways and mitochondrial-mediated intrinsic pathways. We also discuss lysosomal-mediated necrosis and the occurrence of necroptosis following CTX action. Collectively, we provided an insight into concentration-dependent transition of cell death pattern which involves different mechanistic actions. This contributes a new direction for further investigation of cytotoxic pathways activated by the CTXs for future development of biotherapeutics targeting pathological effects caused by CTX.

眼镜蛇毒液细胞毒素(CTX)是一种非酶的三指毒素,占眼镜蛇毒液的40-60%。因此,它在眼镜蛇中毒的病理生理中起重要作用,特别是在局部皮肤坏死中。CTX的三指疏水环决定细胞毒性。然而,细胞毒性的实际机制尚未完全阐明,因为它们不仅涉及细胞溶解作用,还涉及细胞内信号介导的细胞死亡途径。此外,可能的过渡细胞死亡模式仍有待探索。实际的分子机制需要进一步研究,以揭示不同眼镜蛇物种的不同ctx与细胞类型之间的关系,这可能导致不同的细胞死亡模式。在这里,我们讨论了CTX与细胞膜的生物物理相互作用,涉及四种结合模式:静电相互作用、疏水分配、各向同性相和寡聚化。CTX的寡聚化导致膜脂双分子层形成孔。此外,ctx诱导的凋亡途径可以通过死亡受体介导的外在途径和线粒体介导的内在途径来实现。我们还讨论了溶酶体介导的坏死和CTX作用后坏死下垂的发生。总的来说,我们提供了对涉及不同机制作用的细胞死亡模式的浓度依赖性转变的见解。这为进一步研究CTX激活的细胞毒性途径提供了新的方向,为未来开发针对CTX病理作用的生物治疗药物提供了新的思路。
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引用次数: 6
Venom profile of the European carpenter bee Xylocopa violacea: Evolutionary and applied considerations on its toxin components 欧洲木蜂(Xylocopa violacea)的毒液谱:毒素成分的进化和应用考虑
Q2 TOXICOLOGY Pub Date : 2022-06-01 DOI: 10.1016/j.toxcx.2022.100117
Björn M. von Reumont , Sebastien Dutertre , Ivan Koludarov

Modern venomics is increasing its focus on hymenopterans such as honeybees, bumblebees, parasitoid wasps, ants and true wasps. However solitary bees remain understudied in comparison and the few available venom studies focus on short melittin-like sequences and antimicrobial peptides. Herein we describe the first comprehensive venom profile of a solitary bee, the violet carpenter bee Xylocopa violacea, by using proteo-transcriptomics. We reveal a diverse and complex venom profile with 43 different protein families identified from dissected venom gland extracts of which 32 are also detected in the defensively injected venom. Melittin and apamin are the most highly secreted components, followed by Phospholipase A2, Icarapin, Secapin and three novel components. Other components, including eight novel protein families, are rather lowly expressed. We further identify multiple forms of apamin-like peptides. The melittin-like sequences of solitary bees separate into two clades, one comprised most sequences from solitary bees including xylopin (the variant in Xylocopa), while sequences from Lasioglossa appear closer related to melittin-like peptides from Bombus (Bombolittins). Our study suggests that more proteo-transcriptomic data from other solitary bees should be complemented with corresponding genome data to fully understand the evolution and complexity of bee venom proteins, and is of a particular need to disentangle the ambiguous phylogenetic relations of short peptides.

现代基因组学越来越关注膜翅目昆虫,如蜜蜂、大黄蜂、寄生蜂、蚂蚁和真黄蜂。然而,相比之下,对独居蜜蜂的研究仍然不足,而且很少有关于毒液的研究集中在蜂毒蛋白样短序列和抗菌肽上。在这里,我们通过蛋白质转录组学描述了一种孤独的蜜蜂,紫罗兰木匠蜂Xylocopa violacea的第一个全面的毒液特征。我们揭示了一个多样化和复杂的毒液轮廓与43个不同的蛋白质家族鉴定从解剖的毒腺提取物,其中32也检测到防御性注射毒液。Melittin和apamin是分泌最多的成分,其次是磷脂酶A2, Icarapin, Secapin和三个新成分。其他成分,包括8个新的蛋白质家族,表达水平相当低。我们进一步鉴定了多种形式的阿帕胺样肽。独居蜂的蜂毒蛋白样序列分为两个分支,一个分支包含了大部分来自独居蜂的序列,包括xylopin (Xylocopa的变体),而来自Lasioglossa的序列似乎与来自Bombus的蜂毒蛋白样肽(bombolittin)更接近。我们的研究表明,更多来自其他独居蜜蜂的蛋白质转录组学数据应该与相应的基因组数据相补充,以充分了解蜂毒蛋白质的进化和复杂性,特别是需要解开短肽的模糊系统发育关系。
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引用次数: 5
Does probiotic Kefir reduce dyslipidemia, hematological disorders and oxidative stress induced by zearalenone toxicity in wistar rats? 益生菌开非尔是否能降低wistar大鼠由玉米赤霉烯酮中毒引起的血脂异常、血液学紊乱和氧化应激?
Q2 TOXICOLOGY Pub Date : 2022-06-01 DOI: 10.1016/j.toxcx.2022.100121
Fadia Ben Taheur , Chalbia Mansour , Sondes Mechri , Sihem Safta Skhiri , Bassem Jaouadi , Ridha Mzoughi , Kamel Chaieb , Nacim Zouari

Zearalenone (ZEA) is a toxic metabolite of the genus Fusarium, which causes hepatotoxicity and induces oxidative stress. Kefir is an important probiotic dairy-product showing important in vitro antioxidant potential. In this study, the effect of Kefir supplementation to mitigate ZEA toxicity in rats was investigated. Animals were divided into four groups of five rats each, which received sterile milk (200 μL/day) during the first week. Then, they were switched to Kefir (200 μL/day), ZEA (40 mg/kg b. w./day) and Kefir + ZEA for the second week. Hematological and biochemical parameters, as well as liver histological analysis were determined. Kefir administration prevented the changes occurred in the count of all blood cells, and improved the antioxidant enzymes in the liver, such as catalase, glutathione peroxidase and superoxide dismutase activities that increased by 6, 4.5 and 1.3 folds, respectively, compared to ZEA group. Interestingly, the concurrent regimen Kefir + ZEA removed ZEA residues in the serum and liver. Furthermore, the Kefir + ZEA group showed a reduction in the levels of bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and hepatic malonaldehyde by ∼82, 54, 66, 50 and 36%, respectively, compared to the ZEA group. The histopathological analysis showed a normal liver histological architecture in Kefir + ZEA group, while degenerative changes were observed in ZEA group. These results suggest that Kefir as probiotic consortium may have a hepatoprotective effect against ZEA poisoning.

玉米赤霉烯酮(ZEA)是镰刀菌属的一种有毒代谢物,可引起肝毒性并诱导氧化应激。开菲尔是一种重要的益生菌乳制品,具有重要的体外抗氧化潜力。本研究探讨了添加开非尔对大鼠ZEA毒性的影响。动物分为4组,每组5只大鼠,第1周给予200 μL/d的无菌乳。第二周分别饲喂开菲尔(200 μL/d)、ZEA (40 mg/kg b.w. /d)和开菲尔+ ZEA。测定血液学、生化指标及肝脏组织学分析。开非尔能抑制所有血细胞计数的变化,提高肝脏中过氧化氢酶、谷胱甘肽过氧化物酶和超氧化物歧化酶活性,分别比ZEA组提高6倍、4.5倍和1.3倍。有趣的是,同时使用Kefir + ZEA方案可以去除血清和肝脏中的ZEA残留物。此外,与ZEA组相比,Kefir + ZEA组的胆红素、丙氨酸转氨酶、天冬氨酸转氨酶、碱性磷酸酶和肝丙二醛水平分别降低了82%、54%、66%、50%和36%。组织病理学分析显示,Kefir + ZEA组肝脏组织结构正常,ZEA组肝脏组织结构发生退行性改变。上述结果提示,开非尔作为益生菌联合体可能具有抗ZEA中毒的保肝作用。
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引用次数: 2
“At the hospital they do not treat venom from snakebites”: A qualitative assessment of health seeking perspectives and experiences among snakebite victims in Rwanda "在医院,他们不治疗蛇咬伤的毒液":对卢旺达蛇咬伤受害者寻求保健的观点和经验的定性评估
Q2 TOXICOLOGY Pub Date : 2022-06-01 DOI: 10.1016/j.toxcx.2022.100100
Janna M. Schurer , Aleta Dam , Marie Thérèse Mutuyimana , Daniel Muhire Runanira , Richard Nduwayezu , J. Hellen Amuguni

Snakebite envenomation (SBE) is a serious medical condition with human, animal, and environmental factors driving occurrence. In Rwanda, the number of SBE cases reported by the medical system is far lower than regional estimates for SBE incidence, suggesting that victims might be seeking care outside of formal medical structures. Our goals were to describe circumstances surrounding snakebite and to explore experiences of snakebite victims in accessing treatment. For this qualitative study, our team recruited individuals bitten by snakes between 2013 and 2018, who sought care either from traditional healers (N = 40) or hospitals (N = 65). In-depth interviews based on a semi-structured interview guide were conducted by telephone in Kinyarwanda. Inductive thematic analysis was conducted by two team members. Our respondents reported similar environmental circumstances surrounding their snake encounters; namely, farm fields, roads, and their homes, as well as inadequate lighting. Unsafe First Aid practices, including burning/sucking/cutting the skin and tourniquet, were often performed immediately after bites. Respondents reported various reasons for seeking traditional or hospital care, such as perceived cost, distance, transportation, and especially, community beliefs and treatment outcomes of other victims. Respondents described envenomation of livestock as well as the sale of livestock to pay SBE-related medical expenses. Improving trust and use of formal medical services will require enhanced hospital delivery of high quality medical services for SBE through improved stocking of appropriate anti-venom and reduced delays during intake. Communities might also benefit from education campaigns that discourage unsafe First Aid practices and address the common misperception that physicians are not trained to treat SBE.

蛇咬中毒(SBE)是一种严重的疾病,与人类、动物和环境因素有关。在卢旺达,医疗系统报告的SBE病例数量远低于该地区对SBE发病率的估计,这表明受害者可能在正规医疗机构之外寻求治疗。我们的目标是描述蛇咬伤周围的情况,并探索蛇咬伤受害者在获得治疗方面的经历。在这项定性研究中,我们的团队招募了2013年至2018年间被蛇咬伤的个体,他们从传统治疗师(N = 40)或医院(N = 65)那里寻求治疗。根据半结构化访谈指南,在卢旺达通过电话进行了深度访谈。由两名组员进行归纳性专题分析。我们的受访者报告了他们遇到蛇的类似环境;也就是说,农田、道路和他们的家,以及照明不足。不安全的急救做法,包括烧伤/吸吮/切割皮肤和止血带,通常在咬伤后立即进行。答复者报告了寻求传统或医院治疗的各种原因,例如认为费用、距离、交通,特别是社区信仰和其他受害者的治疗结果。受访者描述了对牲畜的毒害以及出售牲畜以支付与sbe相关的医疗费用。提高对正规医疗服务的信任和使用,需要医院通过改善适当抗蛇毒血清的储存和减少摄入期间的延误,加强为SBE提供高质量的医疗服务。社区也可以从教育活动中受益,这些教育活动可以阻止不安全的急救做法,并解决医生没有接受过治疗SBE培训的普遍误解。
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引用次数: 9
Antifungal activity of Rhopalurus crassicauda venom against Candida spp. 荆芥毒对念珠菌的抗真菌活性研究。
Q2 TOXICOLOGY Pub Date : 2022-06-01 DOI: 10.1016/j.toxcx.2022.100120
Umberto Zottich , Isadora Sousa de Oliveira , Isabela Gobbo Fereira , Felipe Augusto Cerni , Bordon Karla de Castro Figueiredo , Eliane Candiani Arantes , Valdirene Moreira Gomes , Germana Bueno Dias , Manuela Berto Pucca

Fungal infections are becoming a serious problem of human diseases, being one of the most important fungal pathogens the yeast of the genus Candida. So far, fungal infection treatment faces different challenges, including the limited number of therapeutic drugs. Scorpions are known to be a valuable source of biologically active molecules, especially of peptide-derived molecules with a variety of biological effects and useful, lead compounds for drugs development. Here, we pioneer described the antifungal effect of venom, mucus, and the major toxin (Rc1) from Rhopalurus crassicauda scorpion. These results support the potential for Rc1 to be further investigated as a novel antifungal therapeutic to treat Candida infections.

念珠菌属酵母菌是最重要的真菌病原体之一,真菌感染已成为人类疾病的一个严重问题。到目前为止,真菌感染的治疗面临着不同的挑战,包括治疗药物的数量有限。蝎子被认为是生物活性分子的宝贵来源,特别是具有多种生物效应的肽衍生分子和有用的药物开发先导化合物。本文首先研究了天蝎毒液、黏液和主要毒素(Rc1)的抗真菌作用。这些结果支持了Rc1作为一种治疗念珠菌感染的新型抗真菌药物的潜力。
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引用次数: 1
Evaluation of lethality and cytotoxic effects induced by Naja ashei (large brown spitting cobra) venom and the envenomation-neutralizing efficacy of selected commercial antivenoms in Kenya 评估肯尼亚大棕色吐痰眼镜蛇(Naja ashei)毒液的致死性和细胞毒性作用,以及选定的商业抗蛇毒血清的毒中和效果
Q2 TOXICOLOGY Pub Date : 2022-06-01 DOI: 10.1016/j.toxcx.2022.100125
Ernest Z. Manson , Mutinda C. Kyama , Joseph K. Gikunju , Josephine Kimani , James H. Kimotho

Neutralization of lethality in mice model at the preclinical level has been established by the World Health Organization as the gold standard for the evaluation of antivenom efficacy. The assessment of the neutralization profiles of antivenoms helps to discern the efficacy or otherwise of these antivenoms at neutralizing the toxic effects induced by medically significant snake venoms. However, for many antivenoms, information on their preclinical efficacy remains limited. Therefore, to strengthen global efforts at reducing the impact of snakebite envenoming, the provision of information on the preclinical efficacy of antivenoms, especially in parts of the world where antivenom availability and accessibility is problematic, including sub-Saharan Africa is crucial. This study presents the lethal and toxic activities of N. ashei venom and the neutralizing capacity of two commonly used commercial antivenoms in Kenya; VINS™ and Inoserp™. Median lethal dose (LD50), minimum necrotizing dose (MND) and minimum edema-forming dose (MED) of N. ashei venom as well as the neutralization of these effects were evaluated in mice. The LD50 of N. ashei venom was found to be 4.67 (3.34–6.54) mg/kg while MND and MED were 11.00 μg and 0.80 μg respectively. Both VINS™ and Inoserp™ antivenoms demonstrated capacity to neutralize the lethal and toxic effects induced by Naja ashei venom albeit at varying efficacies. Our results thus confirm the toxic effects of N. ashei venom as previously observed with other Naja sp. venoms and also underscore the relevance of para-specific neutralizing capacity of antivenoms in the design of antivenoms.

临床前小鼠模型的致死中和已被世界卫生组织确立为评价抗蛇毒血清疗效的金标准。对抗蛇毒血清中和特性的评估有助于辨别这些抗蛇毒血清在中和由医学上重要的蛇毒引起的毒性作用方面的功效。然而,对于许多抗蛇毒血清,关于其临床前疗效的信息仍然有限。因此,为了加强全球减少蛇咬伤影响的努力,提供关于抗蛇毒血清临床前疗效的信息至关重要,特别是在世界上抗蛇毒血清可得性和可及性存在问题的地区,包括撒哈拉以南非洲。本研究提出了致命的和有毒的活动N. ashei蛇毒和中和能力的两种常用的商业抗蛇毒在肯尼亚;VINS™和Inoserp™。在小鼠实验中,评价了灰头蛇毒的中位致死剂量(LD50)、最小坏死剂量(MND)和最小水肿形成剂量(MED)及其中和作用。毒的LD50为4.67 (3.34 ~ 6.54)mg/kg, MND和MED分别为11.00和0.80 μg。VINS™和Inoserp™抗蛇毒血清均显示有能力中和由Naja ashei毒液引起的致命和毒性作用,尽管效果不同。因此,我们的研究结果证实了以前在其他Naja sp.毒液中观察到的ashei N.毒液的毒性作用,并强调了抗蛇毒血清在抗蛇毒血清设计中的准特异性中和能力的相关性。
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引用次数: 2
Venom system variation and the division of labor in the colonial hydrozoan Hydractinia symbiolongicarpus 共生水螅虫毒液系统变异及分工
Q2 TOXICOLOGY Pub Date : 2022-06-01 DOI: 10.1016/j.toxcx.2022.100113
Anna M.L. Klompen , Steven M. Sanders , Paulyn Cartwright

Cnidarians (jellyfish, hydroids, sea anemones, and corals) possess a unique method for venom production, maintenance, and deployment through a decentralized system composed of different types of venom-filled stinging structures called nematocysts. In many species, nematocyst types are distributed heterogeneously across functionally distinct tissues. This has led to a prediction that different nematocyst types contain specific venom components. The colonial hydrozoan, Hydractinia symbiolongicarpus, is an ideal system to study the functional distribution of nematocyst types and their venoms, given that they display a division of labor through functionally distinct polyps within the colony. Here, we characterized the composition and distribution of nematocysts (cnidome) in the different polyp types and show that the feeding polyp (gastrozooid) has a distinct cnidome compared to the reproductive (gonozooid) and predatory polyp (dactylozooid). We generated a nematocyst-specific reporter line to track nematocyst development (nematogenesis) in H. symbiolongicarpus, and were able to confirm that nematogenesis primarily occurs in the mid-region of the gastrozooid and throughout stolons (tubes of epithelia that connect the polyps in the colony). This reporter line enabled us to isolate a nematocyst-specific lineage of cells for de novo transcriptome assembly, annotate venom-like genes (VLGs) and determine differential expression (DE) across polyp types. We show that a majority of VLGs are upregulated in gastrozooids, consistent with it being the primary site of active nematogenesis. However, despite gastrozooids producing more nematocysts, we found a number of VLGs significantly upregulated in dactylozooids, suggesting that these VLGs may be important for prey-capture. Our transgenic Hydractinia reporter line provides an opportunity to explore the complex interplay between venom composition, nematocyst diversity, and ecological partitioning in a colonial hydrozoan that displays a division of labor.

刺胞动物(水母、水螅、海葵和珊瑚)拥有一种独特的毒液产生、维持和释放方法,通过一个分散的系统,由不同类型的充满毒液的刺状结构组成,称为刺丝囊。在许多物种中,线虫囊类型在功能不同的组织中分布不均。这导致了一种预测,即不同类型的刺丝囊含有特定的毒液成分。共生水螅虫(Hydractinia symbiolongicarpus)是研究线虫囊类型及其毒液功能分布的理想系统,因为它们在群体内通过功能不同的息肉表现出分工。本文对不同类型的线虫囊(刺丝囊)的组成和分布进行了分析,结果表明,与生殖型(淋虫型)和掠食性(趾形虫型)相比,食性息肉(胃虫型)具有明显的刺丝囊。我们建立了一个线虫囊特异性报告系来追踪H. symbiolongicarpus的线虫囊发育(线虫发生),并能够证实线虫发生主要发生在腹虫的中部和整个匍匐茎(连接息肉的上皮管)。该报告系使我们能够分离出线虫囊特异性细胞谱系,用于新生转录组组装,注释毒液样基因(VLGs)并确定不同息肉类型的差异表达(de)。我们发现大多数VLGs在腹动物中上调,这与它是活跃的线虫发生的主要部位相一致。然而,尽管腹类动物产生更多的线虫囊,我们发现许多VLGs在趾形动物中显著上调,这表明这些VLGs可能对猎物捕获很重要。我们的转基因水螅报告系提供了一个机会来探索在一个显示劳动分工的水生动物群体中,毒液成分、刺丝囊多样性和生态分配之间复杂的相互作用。
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引用次数: 2
Non-compartmental toxicokinetic studies of the Nigerian Naja nigricollis venom 尼日利亚黑瘤蛇毒液的非室室毒性动力学研究
Q2 TOXICOLOGY Pub Date : 2022-06-01 DOI: 10.1016/j.toxcx.2022.100122
Auwal A. Bala , Sani Malami , Yusuf Abubakar Muhammad , Binta Kurfi , Ismaila Raji , Sanusi Muhammad Salisu , Mustapha Mohammed , George Oche Ambrose , Murtala Jibril , Jacob A. Galan , Elda E. Sanchez , Basheer A.Z. Chedi

Snakebite envenoming (SBE) is a neglected public health problem, especially in Asia, Latin America and Africa. There is inadequate knowledge of venom toxicokinetics especially from African snakes. To mimic a likely scenario of a snakebite envenoming, we used an enzyme-linked immunosorbent assay (ELISA) approach to study the toxicokinetic parameters in rabbits, following a single intramuscular (IM) administration of Northern Nigeria Naja nigricollis venom. We used a developed and validated non-compartmental approach in the R package PK to determine the toxicokinetic parameters of the venom and subsequently used pharmacometrics modelling to predict the movement of the toxin within biological systems. We found that N. nigricollis venom contained sixteen venom protein families following a mass spectrometric analysis of the whole venom. Most of these proteins belong to the three-finger toxins family (3FTx) and venom phospholipase A2 (PLA2) with molecular weight ranging from 3 to 16 kDa. Other venom protein families were in small proportions with higher molecular weights. The N. nigricollis venom was rapidly absorbed at 0.5 h, increased after 1 h and continued to decrease until the 16th hour (Tmax), where maximum concentration (Cmax) was observed. This was followed by a decrease in concentration at the 32nd hour. The venom of N. nigricollis was found to have high volume of distribution (1250 ± 245 mL) and low clearance (29.0 ± 2.5 mL/h) with an elimination half-life of 29 h. The area under the curve (AUC) showed that the venom remaining in the plasma over 32 h was 0.0392 ± 0.0025 mg h.L−1, and the mean residence time was 43.17 ± 8.04 h. The pharmacometrics simulation suggests that the venom toxins were instantly and rapidly absorbed into the extravascular compartment and slowly moved into the central compartment. Our study demonstrates that Nigerian N. nigricollis venom contains low molecular weight toxins that are well absorbed into the blood and deep tissues. The venom could be detected in rabbit blood 48 h after intramuscular envenoming.

蛇咬伤(SBE)是一个被忽视的公共卫生问题,特别是在亚洲、拉丁美洲和非洲。人们对毒液的毒性动力学,特别是非洲蛇的毒性动力学认识不足。为了模拟蛇咬伤的可能场景,我们采用酶联免疫吸附试验(ELISA)方法研究了北尼日利亚奈贾黑毛线虫毒液单次肌肉注射后家兔的毒动力学参数。我们在R包PK中使用了一种经过开发和验证的非区隔方法来确定毒液的毒性动力学参数,随后使用药物计量学建模来预测毒素在生物系统中的运动。通过质谱分析,我们发现黑毛线虫毒液含有16个毒液蛋白家族。这些蛋白大多属于三指毒素家族(3FTx)和毒液磷脂酶A2 (PLA2),分子量在3 ~ 16 kDa之间。其他毒蛋白科所占比例较小,分子量较高。黑毛线虫毒液在0.5 h被迅速吸收,1 h后呈上升趋势,并持续下降至第16小时(Tmax),此时观察到最大浓度(Cmax)。随后在第32小时浓度下降。黑螺旋体毒液分布量大(1250±245 mL),清除率低(29.0±2.5 mL/h),消除半衰期为29 h。曲线下面积(AUC)显示,黑螺旋体毒液在32 h内残留量为0.0392±0.0025 mg h. l−1;平均停留时间为43.17±8.04 h。药理学模拟表明,毒液毒素瞬间迅速被吸收到血管外腔室,缓慢进入中央腔室。我们的研究表明,尼日利亚黑毛线虫毒液含有低分子量的毒素,很好地吸收到血液和深层组织。兔肌注48 h后血中可检出毒。
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