Toxicon: X最新文献

Toxicon and Toxicon: X - Editorial transitions and future directions in 2025

IF 3.6 Q2 TOXICOLOGY

Toxicon: X

Pub Date : 2025-04-11 DOI: 10.1016/j.toxcx.2025.100223

Raymond S. Norton , Denise V. Tambourgi

引用次数: 0

Predictive analysis of B-cell antigenic epitopes in phospholipase D toxins from Loxosceles spiders

IF 3.6 Q2 TOXICOLOGY

Toxicon: X

Pub Date : 2025-03-26 DOI: 10.1016/j.toxcx.2025.100222

Alejandro Catalán , Carolina García , Valentina Sambra , Nicole Cadena , José Rojas , Tomás Arán-Sekul , Juan San Francisco , Valeria Vásquez-Saez , Christian Muñoz , Abel Vásquez , Jorge E. Araya

The Phospholipase D (PLD) toxin family, a major component of the Loxosceles spider venom, is a valuable biotechnological tool for developing antivenom treatment and diagnostic assays to overcome and prevent loxoscelism. However, there is limited knowledge about the antigenic structure of the PLD family or if sequence diversity correlates with antigenic variability. This study aimed to evaluate the possible antigenic diversity of PLDs sequences among different species of spiders of the Loxosceles genus through a predictive analysis of potential continuous and discontinuous antigenic epitopes of two phylogenetic interspecies clusters. Thus, L. laeta had higher amino acid sequence variation than other species, being classified into three phylogenetic clusters at the intra-specie level. Furthermore, multiple alignments of consensus PLD sequences from each Loxosceles species showed two different phylogenetic clusters at interspecies level depending on the amino acid conservation. For each cluster, at least nine continuous antigenic domains were identified, and depending on the phylogenetic cluster belonging to the Loxosceles species, the PLD continuous and discontinuous antigenic structure varies. Also, L. laeta PLDs vary significantly within the Loxosceles species and possess their own antigenic structure compared to other species with common continuous epitopes. Finally, the catalytic loop was identified as a common discontinuous epitope in the PLDs independently of the cluster or the class it belongs to. This antigenic diversity of PLD toxins could have implications for antibody recognition and should be considered in the design strategies for the development of serum treatments and diagnostic assays to detect Loxosceles venom.

{"title":"Predictive analysis of B-cell antigenic epitopes in phospholipase D toxins from Loxosceles spiders","authors":"Alejandro Catalán , Carolina García , Valentina Sambra , Nicole Cadena , José Rojas , Tomás Arán-Sekul , Juan San Francisco , Valeria Vásquez-Saez , Christian Muñoz , Abel Vásquez , Jorge E. Araya","doi":"10.1016/j.toxcx.2025.100222","DOIUrl":"10.1016/j.toxcx.2025.100222","url":null,"abstract":"<div><div>The Phospholipase D (PLD) toxin family, a major component of the <em>Loxosceles</em> spider venom, is a valuable biotechnological tool for developing antivenom treatment and diagnostic assays to overcome and prevent loxoscelism. However, there is limited knowledge about the antigenic structure of the PLD family or if sequence diversity correlates with antigenic variability. This study aimed to evaluate the possible antigenic diversity of PLDs sequences among different species of spiders of the <em>Loxosceles</em> genus through a predictive analysis of potential continuous and discontinuous antigenic epitopes of two phylogenetic interspecies clusters. Thus, <em>L. laeta</em> had higher amino acid sequence variation than other species, being classified into three phylogenetic clusters at the intra-specie level. Furthermore, multiple alignments of consensus PLD sequences from each <em>Loxosceles</em> species showed two different phylogenetic clusters at interspecies level depending on the amino acid conservation. For each cluster, at least nine continuous antigenic domains were identified, and depending on the phylogenetic cluster belonging to the <em>Loxosceles</em> species, the PLD continuous and discontinuous antigenic structure varies. Also, <em>L. laeta</em> PLDs vary significantly within the <em>Loxosceles</em> species and possess their own antigenic structure compared to other species with common continuous epitopes. Finally, the catalytic loop was identified as a common discontinuous epitope in the PLDs independently of the cluster or the class it belongs to. This antigenic diversity of PLD toxins could have implications for antibody recognition and should be considered in the design strategies for the development of serum treatments and diagnostic assays to detect <em>Loxosceles</em> venom.</div></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"26 ","pages":"Article 100222"},"PeriodicalIF":3.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725598","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}

引用次数: 0

Epidemiological and geodemographic patterns of scorpionism in Ecuador: A nationwide analysis (2021–2024)

IF 3.6 Q2 TOXICOLOGY

Toxicon: X

Pub Date : 2025-03-08 DOI: 10.1016/j.toxcx.2025.100218

Jorge Vasconez-Gonzalez , Juan S. Izquierdo-Condoy , Camila Miño , María de Lourdes Noboa-Lasso , Esteban Ortiz-Prado

Background

Approximately 1.2 million scorpion stings are reported globally each year, resulting in an estimated 3000 deaths. Of the 2500 known scorpion species, about 40 are considered medically significant. In Ecuador, where at least 47 scorpion species exist, information on scorpion stings remains scarce.

Methods

A nationwide cross-sectional analysis was conducted on all officially reported cases of scorpion stings documented in the epidemiological surveillance reports from the Ministry of Public Health in Ecuador between 2021 and 2024.

Results

A total of 1633 cases were identified, with women accounting for 52% of cases (n = 849). The highest incidence was observed among children aged one to four years old, with rates of 18.16 and 19.11 per 100,000 inhabitants for males and females, respectively. Geographically, the Amazon region was the most affected, with the province of Morona Santiago reporting the highest incidence at 284.14 cases per 100,000 inhabitants.

Conclusion

Scorpion stings represent a significant and underreported public health threat in Ecuador. This study highlights the considerable disease burden, particularly in specific regions of the country, and underscores the urgent need for targeted public health interventions and policy changes, including the local production of antivenoms.

{"title":"Epidemiological and geodemographic patterns of scorpionism in Ecuador: A nationwide analysis (2021–2024)","authors":"Jorge Vasconez-Gonzalez , Juan S. Izquierdo-Condoy , Camila Miño , María de Lourdes Noboa-Lasso , Esteban Ortiz-Prado","doi":"10.1016/j.toxcx.2025.100218","DOIUrl":"10.1016/j.toxcx.2025.100218","url":null,"abstract":"<div><h3>Background</h3><div>Approximately 1.2 million scorpion stings are reported globally each year, resulting in an estimated 3000 deaths. Of the 2500 known scorpion species, about 40 are considered medically significant. In Ecuador, where at least 47 scorpion species exist, information on scorpion stings remains scarce.</div></div><div><h3>Methods</h3><div>A nationwide cross-sectional analysis was conducted on all officially reported cases of scorpion stings documented in the epidemiological surveillance reports from the Ministry of Public Health in Ecuador between 2021 and 2024.</div></div><div><h3>Results</h3><div>A total of 1633 cases were identified, with women accounting for 52% of cases (n = 849). The highest incidence was observed among children aged one to four years old, with rates of 18.16 and 19.11 per 100,000 inhabitants for males and females, respectively. Geographically, the Amazon region was the most affected, with the province of Morona Santiago reporting the highest incidence at 284.14 cases per 100,000 inhabitants.</div></div><div><h3>Conclusion</h3><div>Scorpion stings represent a significant and underreported public health threat in Ecuador. This study highlights the considerable disease burden, particularly in specific regions of the country, and underscores the urgent need for targeted public health interventions and policy changes, including the local production of antivenoms.</div></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"26 ","pages":"Article 100218"},"PeriodicalIF":3.6,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143601758","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}

引用次数: 0

Methods matter: Comparison of techniques used for sea anemone venom extraction

IF 3.6 Q2 TOXICOLOGY

Toxicon: X

Pub Date : 2025-03-08 DOI: 10.1016/j.toxcx.2025.100219

K.L. Kaposi , D.T. Wilson , A. Jones , J.E. Seymour

The study of cnidarian (coral, sea anemone, and jellyfish) venom provides important evolutionary and ecological insights and unlocks vast opportunities for biodiscovery of novel compounds. The success of the field is dependent on not only the acquisition of sufficient quantities of venom but also the ability to compare venom between species and studies. To date, no direct comparison of the main techniques used to acquire sea anemone venom has been performed to determine the comparability or validity of these methods to yield venom derived from within cnidarian venom apparatus – cnidae. This study aims to compare the venom extracted from a sea anemone via three common methods: isolated cnidae, electrostimulation, and physical manipulation. Using a range of non-targeted proteomic and mass spectrometric techniques, we showed each method yielded distinct differences in both the composition and abundance of components detected for extraction method. Furthermore, few identified components were shared between each of the extraction methods. These results highlight that different venom collection methods yield vastly different results. While further investigation is required, to validate the source of each of the components from within each sample, we argue that sample collection from isolated cnidae is likely to be the most representative of true venom components.

{"title":"Methods matter: Comparison of techniques used for sea anemone venom extraction","authors":"K.L. Kaposi , D.T. Wilson , A. Jones , J.E. Seymour","doi":"10.1016/j.toxcx.2025.100219","DOIUrl":"10.1016/j.toxcx.2025.100219","url":null,"abstract":"<div><div>The study of cnidarian (coral, sea anemone, and jellyfish) venom provides important evolutionary and ecological insights and unlocks vast opportunities for biodiscovery of novel compounds. The success of the field is dependent on not only the acquisition of sufficient quantities of venom but also the ability to compare venom between species and studies. To date, no direct comparison of the main techniques used to acquire sea anemone venom has been performed to determine the comparability or validity of these methods to yield venom derived from within cnidarian venom apparatus – cnidae. This study aims to compare the venom extracted from a sea anemone via three common methods: isolated cnidae, electrostimulation, and physical manipulation. Using a range of non-targeted proteomic and mass spectrometric techniques, we showed each method yielded distinct differences in both the composition and abundance of components detected for extraction method. Furthermore, few identified components were shared between each of the extraction methods. These results highlight that different venom collection methods yield vastly different results. While further investigation is required, to validate the source of each of the components from within each sample, we argue that sample collection from isolated cnidae is likely to be the most representative of true venom components.</div></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"26 ","pages":"Article 100219"},"PeriodicalIF":3.6,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143611721","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}

引用次数: 0

A comparative analysis of toxin gene families across diverse sea anemone species

IF 3.6 Q2 TOXICOLOGY

Toxicon: X

Pub Date : 2025-03-07 DOI: 10.1016/j.toxcx.2025.100217

Hayden L. Smith , Daniel A. Broszczak , Chloé A. van der Burg , Joachim M. Surm , Libby Liggins , Raymond S. Norton , Peter J. Prentis

All species from order Actiniaria (sea anemones) are venomous, even though most are of no threat to humans. Currently, we know very little about the toxin gene complement of highly venomous members of this order. To address this gap in knowledge, we sequenced the transcriptome of the highly venomous and medically significant Hell's Fire sea anemone, Actinodendron plumosum, as well as five distantly related species, Cryptodendrum adhaesivum, Epiactis australiensis, Heteractis aurora, Isactinia olivacea and Stichodactyla mertensii. We used bioinformatic approaches to identify their toxin gene complements and performed a comparative evolutionary analysis of seven understudied toxin families. Of the 16 toxin families identified, 12–40 candidate toxins were found in the six new sea anemone transcriptomes, with only 12 candidates in eight toxin families identified in A. plumosum. Across 26 sea anemone species, six neurotoxin families showed evidence of taxonomic restriction, whereas the phospholipase A2 toxin family was ubiquitously distributed. Additionally, we identified two alternative forms for the phospholipase A2 toxin family, a 10- and 14-cysteine framework, which warrant further structural and functional characterisation. Overall, we have identified a comprehensive list of toxins from a wide diversity of sea anemone species that provides the basis for future research to structurally and functionally characterise novel candidates for potential use as therapeutics or for agricultural applications.

海葵目（Actiniaria）的所有物种都有毒，尽管大多数物种对人类没有威胁。目前，我们对该目剧毒成员的毒素基因补体知之甚少。为了填补这一知识空白，我们对剧毒且在医学上具有重要意义的地狱之火海葵（Actinodendron plumosum）以及五个远缘物种（Cryptodendrum adhaesivum、Epiactis australiensis、Heteractis aurora、Isactinia olivacea 和 Stichodactyla mertensii）的转录组进行了测序。我们利用生物信息学方法确定了它们的毒素基因补体，并对七个研究不足的毒素家族进行了比较进化分析。在鉴定出的 16 个毒素家族中，有 12-40 个候选毒素在 6 个新海葵转录组中被发现，而在 A. plumosum 中仅鉴定出 8 个毒素家族中的 12 个候选毒素。在 26 个海葵物种中，有 6 个神经毒素家族显示出分类限制的证据，而磷脂酶 A2 毒素家族则普遍分布。此外，我们还发现了磷脂酶 A2 毒素家族的两种替代形式--10-半胱氨酸框架和 14-半胱氨酸框架，这两种形式的结构和功能特征值得进一步研究。总之，我们从种类繁多的海葵物种中鉴定出了一份全面的毒素清单，为今后研究新型候选毒素的结构和功能特性提供了基础，这些毒素可能被用作治疗剂或农业应用。

{"title":"A comparative analysis of toxin gene families across diverse sea anemone species","authors":"Hayden L. Smith , Daniel A. Broszczak , Chloé A. van der Burg , Joachim M. Surm , Libby Liggins , Raymond S. Norton , Peter J. Prentis","doi":"10.1016/j.toxcx.2025.100217","DOIUrl":"10.1016/j.toxcx.2025.100217","url":null,"abstract":"<div><div>All species from order Actiniaria (sea anemones) are venomous, even though most are of no threat to humans. Currently, we know very little about the toxin gene complement of highly venomous members of this order. To address this gap in knowledge, we sequenced the transcriptome of the highly venomous and medically significant Hell's Fire sea anemone, <em>Actinodendron plumosum</em>, as well as five distantly related species, <em>Cryptodendrum adhaesivum</em>, <em>Epiactis australiensis</em>, <em>Heteractis aurora</em>, <em>Isactinia olivacea</em> and <em>Stichodactyla mertensii</em>. We used bioinformatic approaches to identify their toxin gene complements and performed a comparative evolutionary analysis of seven understudied toxin families. Of the 16 toxin families identified, 12–40 candidate toxins were found in the six new sea anemone transcriptomes, with only 12 candidates in eight toxin families identified in <em>A. plumosum</em>. Across 26 sea anemone species, six neurotoxin families showed evidence of taxonomic restriction, whereas the phospholipase A2 toxin family was ubiquitously distributed. Additionally, we identified two alternative forms for the phospholipase A2 toxin family, a 10- and 14-cysteine framework, which warrant further structural and functional characterisation. Overall, we have identified a comprehensive list of toxins from a wide diversity of sea anemone species that provides the basis for future research to structurally and functionally characterise novel candidates for potential use as therapeutics or for agricultural applications.</div></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"26 ","pages":"Article 100217"},"PeriodicalIF":3.6,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143621280","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}

引用次数: 0

Oligomer assembly of Bacillus thuringiensis Cyt2Aa2 on lipid membranes reveals a thread-like structure

IF 3.6 Q2 TOXICOLOGY

Toxicon: X

Pub Date : 2025-03-07 DOI: 10.1016/j.toxcx.2025.100220

Chontida Tangsongcharoen , Jose L. Toca-Herrera , Boonhiang Promdonkoy , Kanokporn Srisucharitpanit , Sudarat Tharad

Bacillus thuringiensis, a well-known insecticidal bacterium, produces several insecticidal proteins, including cytolytic (Cyt) proteins. Cyt proteins bind directly to the lipid membrane and form large protein complexes. In addition to the protein ladder bands, information on the oligomeric structure in lipid membranes is necessary to understand the mechanism of Cyt proteins on target cells. In this work, we have investigated the oligomeric Cyt2Aa2 complex with synthetic lipid and with erythrocyte membranes. When the activated Cyt2Aa2 protein was incubated with these lipid membranes, the protein ladder pattern relevant to hemolytic activity was detected in SDS-PAGE. Moreover, AFM topographic images revealed a fusilli-like structure and a ring-like structure for synthetic POPC and POPC/Chol, respectively. Furthermore, TEM micrographs provided an additional information on the oligomeric structure of Cyt2Aa2 in erythrocytes. Cyt2Aa2 appears to oligomerise/aggregate into mixed structures between the filamentous structure and small protein complexes in erythrocytes. In addition, a nanopore was found to be a substructure of the filamentous structure. These results strengthen the understanding of Cyt2Aa2 behavior in these two membrane systems, the fusilli and ring-like structures, depending on the type of lipid membrane. Furthermore, the structure of Cyt2Aa2 in insect target membranes remains to be investigated.

{"title":"Oligomer assembly of Bacillus thuringiensis Cyt2Aa2 on lipid membranes reveals a thread-like structure","authors":"Chontida Tangsongcharoen , Jose L. Toca-Herrera , Boonhiang Promdonkoy , Kanokporn Srisucharitpanit , Sudarat Tharad","doi":"10.1016/j.toxcx.2025.100220","DOIUrl":"10.1016/j.toxcx.2025.100220","url":null,"abstract":"<div><div><em>Bacillus thuringiensis</em>, a well-known insecticidal bacterium, produces several insecticidal proteins, including cytolytic (Cyt) proteins. Cyt proteins bind directly to the lipid membrane and form large protein complexes. In addition to the protein ladder bands, information on the oligomeric structure in lipid membranes is necessary to understand the mechanism of Cyt proteins on target cells. In this work, we have investigated the oligomeric Cyt2Aa2 complex with synthetic lipid and with erythrocyte membranes. When the activated Cyt2Aa2 protein was incubated with these lipid membranes, the protein ladder pattern relevant to hemolytic activity was detected in SDS-PAGE. Moreover, AFM topographic images revealed a fusilli-like structure and a ring-like structure for synthetic POPC and POPC/Chol, respectively. Furthermore, TEM micrographs provided an additional information on the oligomeric structure of Cyt2Aa2 in erythrocytes. Cyt2Aa2 appears to oligomerise/aggregate into mixed structures between the filamentous structure and small protein complexes in erythrocytes. In addition, a nanopore was found to be a substructure of the filamentous structure. These results strengthen the understanding of Cyt2Aa2 behavior in these two membrane systems, the fusilli and ring-like structures, depending on the type of lipid membrane. Furthermore, the structure of Cyt2Aa2 in insect target membranes remains to be investigated.</div></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"26 ","pages":"Article 100220"},"PeriodicalIF":3.6,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143593361","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}

引用次数: 0

Biochemical characterization of the venom of the Bolivian endemic pit viper Bothrops sanctaecrucis

IF 3.6 Q2 TOXICOLOGY

Toxicon: X

Pub Date : 2025-03-01 DOI: 10.1016/j.toxcx.2025.100216

Kevin Lobo-López , Matías E. Martínez , Micaela A. Gritti , María E. Peichoto

Ophidic accidents are an important public health problem in South America, specifically those related to the Bothrops genus, due to their high incidence, complexity and severity of envenomation symptoms. The species B. sanctaecrucis, the only one from this genus endemic to Bolivia, is the most frequently found and involved in snakebites in the Chapare region of Cochabamba; however, its toxicological implications on human health are poorly known. Herein we conducted the first biochemical characterization of its venom. Its electrophoretic profile showed components mainly ranging from ∼10 to 37 kDa, resembling other Bothrops venoms. The venom exhibited high activity on azocasein (47.65 U/mg) and the thrombin-specific substrate S-2238 (625.55 μmol/min/mg), and noticeably hydrolyzed gelatin and human fibrin(ogen). The venom also degraded lecithin and hyaluronic acid, but both at low levels. These in vitro results point out a toxic mechanism of action fundamentally at a local level, with tissue damage likely caused (although not exclusively) by SVMPs. Immunochemical reactivity was evaluated against Bothrops antivenoms produced in Argentina, which not only exhibited cross-reaction by Western Blotting but also neutralized the procoagulant activity of the venom. This study offers first insights into the venom components of B. sanctaecrucis, and provides preliminary and important information about the pathophysiological mechanisms involved in the envenomation by this species, paving the way for treatment strategies in such accidents.

{"title":"Biochemical characterization of the venom of the Bolivian endemic pit viper Bothrops sanctaecrucis","authors":"Kevin Lobo-López , Matías E. Martínez , Micaela A. Gritti , María E. Peichoto","doi":"10.1016/j.toxcx.2025.100216","DOIUrl":"10.1016/j.toxcx.2025.100216","url":null,"abstract":"<div><div>Ophidic accidents are an important public health problem in South America, specifically those related to the <em>Bothrops</em> genus, due to their high incidence, complexity and severity of envenomation symptoms. The species <em>B. sanctaecrucis</em>, the only one from this genus endemic to Bolivia, is the most frequently found and involved in snakebites in the Chapare region of Cochabamba; however, its toxicological implications on human health are poorly known. Herein we conducted the first biochemical characterization of its venom. Its electrophoretic profile showed components mainly ranging from ∼10 to 37 kDa, resembling other <em>Bothrops</em> venoms. The venom exhibited high activity on azocasein (47.65 U/mg) and the thrombin-specific substrate S-2238 (625.55 μmol/min/mg), and noticeably hydrolyzed gelatin and human fibrin(ogen). The venom also degraded lecithin and hyaluronic acid, but both at low levels. These <em>in vitro</em> results point out a toxic mechanism of action fundamentally at a local level, with tissue damage likely caused (although not exclusively) by SVMPs. Immunochemical reactivity was evaluated against <em>Bothrops</em> antivenoms produced in Argentina, which not only exhibited cross-reaction by Western Blotting but also neutralized the procoagulant activity of the venom. This study offers first insights into the venom components of <em>B. sanctaecrucis</em>, and provides preliminary and important information about the pathophysiological mechanisms involved in the envenomation by this species, paving the way for treatment strategies in such accidents.</div></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"25 ","pages":"Article 100216"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143519230","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}

引用次数: 0

Drugs from poisonous plants: Ethnopharmacological relevance to modern perspectives

IF 3.6 Q2 TOXICOLOGY

Toxicon: X

Pub Date : 2025-01-28 DOI: 10.1016/j.toxcx.2025.100215

Bhagya Lakhmi Rajbongshi , Ashis K. Mukherjee

The world of plant diversity is endlessly fascinating and essential for life on Earth. Since the inception of early civilization, humans have utilized plants for several purposes, particularly for their medicinal value. While some plants are known for their toxicity, they also contain beneficial phytochemicals that are important for both plants and humans, indicating their dual nature. This study aims to explore and synthesize the existing knowledge on various poisonous plant species found worldwide. It primarily focuses on the therapeutic potential of specific types of phytochemicals responsible for treating multiple diseases. This review includes a list of 70 poisonous plants with medicinal properties for treating various ailments, as well as some of their traditional uses. A few of these plants are emphasized, which have been tremendously explored and studied, hold significant potential to contribute to modern drug discovery. Furthermore, it addresses the possible prospects and challenges of using poisonous plants and their phytochemicals as therapeutic agents. Although the therapeutic potential of poisonous plants is substantial, many toxins remain unexplored. This review accentuates the need for rigorous scientific investigations, prior to clinical trials to validate their traditional uses, which would reveal the pharmacological interventions that will eventually advance human health and well-being.

{"title":"Drugs from poisonous plants: Ethnopharmacological relevance to modern perspectives","authors":"Bhagya Lakhmi Rajbongshi , Ashis K. Mukherjee","doi":"10.1016/j.toxcx.2025.100215","DOIUrl":"10.1016/j.toxcx.2025.100215","url":null,"abstract":"<div><div>The world of plant diversity is endlessly fascinating and essential for life on Earth. Since the inception of early civilization, humans have utilized plants for several purposes, particularly for their medicinal value. While some plants are known for their toxicity, they also contain beneficial phytochemicals that are important for both plants and humans, indicating their dual nature. This study aims to explore and synthesize the existing knowledge on various poisonous plant species found worldwide. It primarily focuses on the therapeutic potential of specific types of phytochemicals responsible for treating multiple diseases. This review includes a list of 70 poisonous plants with medicinal properties for treating various ailments, as well as some of their traditional uses. A few of these plants are emphasized, which have been tremendously explored and studied, hold significant potential to contribute to modern drug discovery. Furthermore, it addresses the possible prospects and challenges of using poisonous plants and their phytochemicals as therapeutic agents. Although the therapeutic potential of poisonous plants is substantial, many toxins remain unexplored. This review accentuates the need for rigorous scientific investigations, prior to clinical trials to validate their traditional uses, which would reveal the pharmacological interventions that will eventually advance human health and well-being.</div></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"25 ","pages":"Article 100215"},"PeriodicalIF":3.6,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143157119","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}

引用次数: 0

Feasibility study: Varespladib protects CD-1 mice from lethal doses of whole bee (Apis mellifera) venom

IF 3.6 Q2 TOXICOLOGY

Toxicon: X

Pub Date : 2025-01-13 DOI: 10.1016/j.toxcx.2025.100214

James Hearth , Kaitlin Linne , Jerry Harrison , Hossein Zolfaghari , Matthew R. Lewin

Swarming Hymenoptera attacks can deliver high cumulative doses of venom resulting in death and life-threatening or chronically disabling injuries. Varespladib, a potent inhibitor of snake venom secretory PLA2 (sPLA2), is a relatively weak inhibitor of whole bee venom sPLA2 in vitro (pico-to low nanomolar for snake venom compared to

μ

M for Apis millera). Animal studies of varespladib against wasp (Vespa mandarinia) venom have shown promise against both nephropathy and coagulopathy, major markers of severe systemic toxicity distinct from hypersensitivity such as anaphylactoid and anaphylaxis reactions. We conducted a simple pilot study to evaluate if varespladib could feasibly decrease mortality against lethal doses of honeybee (Apis mellifera) venom in a murine model. When pre-mixed with a single dose of 10 mg/kg varespladib and administered intravenously (IV), varespladib prevented all mortality (0 of 10) in comparison to a cohort of mice administered lethal doses of whole bee venom alone (6 of 10) during a 24-h study period (N = 10 each group; log rank χ² = 8.29; p < 0.005), and it eliminated signs of toxicity within 2 h while control animals either died or continued to show signs of toxicity. Survival in these animals despite poor in vitro sPLA2 inhibition suggests that suppression of the host sPLA2 response itself might play a role in the treatment of venom toxicity using an enzyme inhibitor rather than antivenom antibodies. Varespladib could be a useful tool for dissecting fundamental interactions between exogenous toxins and their corresponding endogenous counterparts.

{"title":"Feasibility study: Varespladib protects CD-1 mice from lethal doses of whole bee (Apis mellifera) venom","authors":"James Hearth , Kaitlin Linne , Jerry Harrison , Hossein Zolfaghari , Matthew R. Lewin","doi":"10.1016/j.toxcx.2025.100214","DOIUrl":"10.1016/j.toxcx.2025.100214","url":null,"abstract":"<div><div>Swarming Hymenoptera attacks can deliver high cumulative doses of venom resulting in death and life-threatening or chronically disabling injuries. Varespladib, a potent inhibitor of snake venom secretory PLA2 (sPLA2), is a relatively weak inhibitor of whole bee venom sPLA2 <em>in vitro</em> (pico-to low nanomolar for snake venom compared to <span><math><mrow><mi>μ</mi></mrow></math></span> M for <em>Apis millera</em>). Animal studies of varespladib against wasp (<em>Vespa mandarinia</em>) venom have shown promise against both nephropathy and coagulopathy, major markers of severe systemic toxicity distinct from hypersensitivity such as anaphylactoid and anaphylaxis reactions. We conducted a simple pilot study to evaluate if varespladib could feasibly decrease mortality against lethal doses of honeybee (<em>Apis mellifera</em>) venom in a murine model. When pre-mixed with a single dose of 10 mg/kg varespladib and administered intravenously (IV), varespladib prevented all mortality (0 of 10) in comparison to a cohort of mice administered lethal doses of whole bee venom alone (6 of 10) during a 24-h study period (N = 10 each group; log rank χ<sup>2</sup> = 8.29; p < 0.005), and it eliminated signs of toxicity within 2 h while control animals either died or continued to show signs of toxicity. Survival in these animals despite poor <em>in vitro</em> sPLA2 inhibition suggests that suppression of the host sPLA2 response itself might play a role in the treatment of venom toxicity using an enzyme inhibitor rather than antivenom antibodies. Varespladib could be a useful tool for dissecting fundamental interactions between exogenous toxins and their corresponding endogenous counterparts.</div></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"25 ","pages":"Article 100214"},"PeriodicalIF":3.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143157118","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}

引用次数: 0

A polygeneric immunogen composed of 22 venoms from sub-Saharan African snakes to expand the neutralization scope of the EchiTAb-plus-ICP antivenom 由 22 种撒哈拉以南非洲蛇类毒液组成的多基因免疫原，可扩大 EchiTAb-plus-ICP 抗蛇毒血清的中和范围

IF 3.6 Q2 TOXICOLOGY

Toxicon: X

Pub Date : 2024-11-16 DOI: 10.1016/j.toxcx.2024.100213

Andrés Sánchez, Gina Durán, Maykel Cerdas, Jairo Gutiérrez, Álvaro Segura, María Herrera, Mariángela Vargas, Adriana Sánchez, Paola Sánchez, Gabriela Solano, Mauren Villalta, Edwin Moscoso, Deibid Umaña, Mauricio Arguedas, Aarón Gómez, José María Gutiérrez, Guillermo León

Recent research suggests that a polygeneric immunogen made from the venoms of the most medically important viperid and elapid snakes in sub-Saharan Africa could elicit a broader antibody response in horses compared to the current EchiTAb-plus-ICP antivenom, especially against neurotoxic elapid venoms. To test this, 25 horses that have been regularly immunized to produce this antivenom were reimmunized with an immunogen containing 22 venoms from various snake species from the genera Bitis, Echis, Dendroaspis, and both spitting and non-spitting Naja. The plasma collected from these horses was processed using the caprylic acid method to produce an industrial-scale freeze-dried antivenom. The anti-lethal neutralization scope of this new formulation was then compared to that of EchiTAb-plus-ICP which is designed to target the venoms of Bitis arietans, Echis ocellatus, Naja nigricollis, and Dendroaspis polylepis. The results indicated that adding more venoms to the immunogen did not significantly enhance the neutralization of the lethal effect of viperid venoms (except for Bitis nasicornis) or of venoms of spitting cobras (except for Naja katiensis). However, incorporating additional venoms from non-spitting neurotoxic Naja spp. and Dendroaspis spp. improved the neutralization scope of EchiTAb-plus-ICP against these neurotoxic venoms. The antivenom generated showed a wider anti-lethal neutralizing scope, as compared to the standard EchiTAb-plus-ICP antivenom and constitutes a good candidate to be tested in clinical trials in sub-Saharan Africa.

最近的研究表明，与目前的EchiTAb-plus-ICP抗蛇毒血清相比，一种由撒哈拉以南非洲医学上最重要的蝰蛇和伶毒蛇毒液制成的多属免疫原可在马匹体内引起更广泛的抗体反应，尤其是针对神经毒性伶毒蛇毒液的抗体反应。为了验证这一点，用含有 22 种毒液的免疫原对 25 匹定期免疫以生产这种抗蛇毒血清的马进行了再免疫，这些毒液来自 Bitis 属、Echis 属、Dendroaspis 属以及会吐和不会吐的 Naja 属的各种蛇类。从这些马身上采集的血浆经辛酸法处理后，制成了工业规模的冻干抗蛇毒血清。然后将这种新制剂的抗致命中和范围与 EchiTAb-plus-ICP 的抗致命中和范围进行了比较，后者是针对 Bitis arietans、Echis ocellatus、Naja nigricollis 和 Dendroaspis polylepis 的毒液而设计的。结果表明，在免疫原中加入更多毒液并不能显著增强对蝰蛇毒（鼻角蝰除外）或吐毒眼镜蛇毒（卡提蛇除外）致死效应的中和作用。然而，加入了更多的非吐丝神经毒性眼镜蛇毒液后，EchiTAb-plus-ICP 对这些神经毒性毒液的中和范围得到了改善。与标准的 EchiTAb-plus-ICP 抗蛇毒血清相比，生成的抗蛇毒血清显示出更大的抗致命中和范围，是在撒哈拉以南非洲进行临床试验的理想候选物质。

{"title":"A polygeneric immunogen composed of 22 venoms from sub-Saharan African snakes to expand the neutralization scope of the EchiTAb-plus-ICP antivenom","authors":"Andrés Sánchez, Gina Durán, Maykel Cerdas, Jairo Gutiérrez, Álvaro Segura, María Herrera, Mariángela Vargas, Adriana Sánchez, Paola Sánchez, Gabriela Solano, Mauren Villalta, Edwin Moscoso, Deibid Umaña, Mauricio Arguedas, Aarón Gómez, José María Gutiérrez, Guillermo León","doi":"10.1016/j.toxcx.2024.100213","DOIUrl":"10.1016/j.toxcx.2024.100213","url":null,"abstract":"<div><div>Recent research suggests that a polygeneric immunogen made from the venoms of the most medically important viperid and elapid snakes in sub-Saharan Africa could elicit a broader antibody response in horses compared to the current EchiTAb-plus-ICP antivenom, especially against neurotoxic elapid venoms. To test this, 25 horses that have been regularly immunized to produce this antivenom were reimmunized with an immunogen containing 22 venoms from various snake species from the genera <em>Bitis</em>, <em>Echis</em>, <em>Dendroaspis</em>, and both spitting and non-spitting <em>Naja</em>. The plasma collected from these horses was processed using the caprylic acid method to produce an industrial-scale freeze-dried antivenom. The anti-lethal neutralization scope of this new formulation was then compared to that of EchiTAb-plus-ICP which is designed to target the venoms of <em>Bitis arietans</em>, <em>Echis ocellatus</em>, <em>Naja nigricollis</em>, and <em>Dendroaspis polylepis</em>. The results indicated that adding more venoms to the immunogen did not significantly enhance the neutralization of the lethal effect of viperid venoms (except for <em>Bitis nasicornis</em>) or of venoms of spitting cobras (except for <em>Naja katiensis</em>). However, incorporating additional venoms from non-spitting neurotoxic <em>Naja</em> spp. and <em>Dendroaspis</em> spp. improved the neutralization scope of EchiTAb-plus-ICP against these neurotoxic venoms. The antivenom generated showed a wider anti-lethal neutralizing scope, as compared to the standard EchiTAb-plus-ICP antivenom and constitutes a good candidate to be tested in clinical trials in sub-Saharan Africa.</div></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"24 ","pages":"Article 100213"},"PeriodicalIF":3.6,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142704511","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}

引用次数: 0