Pub Date : 2025-06-01Epub Date: 2025-03-08DOI: 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":"2025-06-01","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}
Pub Date : 2025-06-01Epub Date: 2025-03-07DOI: 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":"2025-06-01","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}
Pub Date : 2025-03-01Epub Date: 2025-01-28DOI: 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":"2025-03-01","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}
Pub Date : 2025-03-01Epub Date: 2025-01-13DOI: 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 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":"2025-03-01","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}
Pub Date : 2025-03-01Epub Date: 2025-02-18DOI: 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}
Pub Date : 2024-12-01Epub Date: 2024-08-30DOI: 10.1016/j.toxcx.2024.100206
Álvaro Segura, Edwin Moscoso, Deibid Umaña, Mariángela Vargas, Andrés Sánchez, Andrés Hernández, Gina Durán, Mauren Villalta, Aarón Gómez, María Herrera, Mauricio Arguedas, José María Gutiérrez, Guillermo León
Snakebite in the Middle East and North Africa (MENA) is a public health problem whose magnitude is not fully known. Several antivenoms are available in these regions, but these formulations are designed for restricted geographical settings. Many countries do not have local production of antivenoms and must access products whose clinical performance has not been demonstrated. We hypothesize that it is possible to unify the treatment for viperid snakebites of MENA in a single antivenom formulation. Hereby we describe the design, development and preclinical evaluation of an antivenom of broad geographical coverage for this region (MENAVip-ICP). We produced this antivenom from the plasma of horses immunized with eight medically important venoms of viperid snake species from MENA. For this, we used a strategy based on two stages: first, immunization of horses with North African (NA) venoms, followed by a second immunization stage, on the same horses, with MENA venoms. We purified antivenoms from both stages: the Anti-NA and the final product Anti-MENA (MENAVip-ICP). Anti-NA was considered as intermediate formulation and was purified with the intention to study the progression of the immunoglobulin immune response of the horses. Antivenoms from both stages neutralized lethal, hemorrhagic, and procoagulant activities of homologous venoms. Compared to Anti-NA, MENAVip-ICP improved the neutralization profile of intravenous lethality and in vitro procoagulant activities of venoms. A notable finding was the difference in the neutralization of lethality when MENAVip-ICP was assessed intraperitoneally versus intravenously in the murine model. Intraperitoneally, MENAVip-ICP appears more effective in neutralizing the lethality of all venoms. Furthermore, MENAVip-ICP neutralized the lethal activity of venoms of species from other regions of MENA, Central/East Asia, and Sub-Saharan Africa that were not included in the immunization protocol. Our results showed that MENAVip-ICP neutralizes the main toxic activities induced by viperid MENA venoms at the preclinical level. Consequently, it is a promising product that could be clinically assessed for the treatment of snakebite envenomings in this region.
{"title":"Design, development and preclinical assessment of MENAVip-ICP, a new snake antivenom with potential coverage of species in the Middle East and North Africa regions","authors":"Álvaro Segura, Edwin Moscoso, Deibid Umaña, Mariángela Vargas, Andrés Sánchez, Andrés Hernández, Gina Durán, Mauren Villalta, Aarón Gómez, María Herrera, Mauricio Arguedas, José María Gutiérrez, Guillermo León","doi":"10.1016/j.toxcx.2024.100206","DOIUrl":"10.1016/j.toxcx.2024.100206","url":null,"abstract":"<div><p>Snakebite in the Middle East and North Africa (MENA) is a public health problem whose magnitude is not fully known. Several antivenoms are available in these regions, but these formulations are designed for restricted geographical settings. Many countries do not have local production of antivenoms and must access products whose clinical performance has not been demonstrated. We hypothesize that it is possible to unify the treatment for viperid snakebites of MENA in a single antivenom formulation. Hereby we describe the design, development and preclinical evaluation of an antivenom of broad geographical coverage for this region (MENAVip-ICP). We produced this antivenom from the plasma of horses immunized with eight medically important venoms of viperid snake species from MENA. For this, we used a strategy based on two stages: first, immunization of horses with North African (NA) venoms, followed by a second immunization stage, on the same horses, with MENA venoms. We purified antivenoms from both stages: the Anti-NA and the final product Anti-MENA (MENAVip-ICP). Anti-NA was considered as intermediate formulation and was purified with the intention to study the progression of the immunoglobulin immune response of the horses. Antivenoms from both stages neutralized lethal, hemorrhagic, and procoagulant activities of homologous venoms. Compared to Anti-NA, MENAVip-ICP improved the neutralization profile of intravenous lethality and <em>in vitro</em> procoagulant activities of venoms. A notable finding was the difference in the neutralization of lethality when MENAVip-ICP was assessed intraperitoneally versus intravenously in the murine model. Intraperitoneally, MENAVip-ICP appears more effective in neutralizing the lethality of all venoms. Furthermore, MENAVip-ICP neutralized the lethal activity of venoms of species from other regions of MENA, Central/East Asia, and Sub-Saharan Africa that were not included in the immunization protocol. Our results showed that MENAVip-ICP neutralizes the main toxic activities induced by viperid MENA venoms at the preclinical level. Consequently, it is a promising product that could be clinically assessed for the treatment of snakebite envenomings in this region.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"24 ","pages":"Article 100206"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171024000237/pdfft?md5=ec6d45a05b83dcdfb12958b3bde3d8de&pid=1-s2.0-S2590171024000237-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142130117","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 : 2024-12-01Epub Date: 2024-09-16DOI: 10.1016/j.toxcx.2024.100208
Diane A. Mielewczyk , Chris N. Glover , Gavin N. Saari
Under climate change scenarios freshwater eutrophication is expected to increase, and with it the occurrence of cyanobacterial toxin-producing harmful algal blooms. In the current study, microcystin toxin occurrence data from literature sources and a long-term provincial monitoring program were used to conduct a probabilistic hazard assessment for Alberta, Canada. The large temporal and spatial range of data makes Alberta a model system for identifying regional geography and water body trophic status factors driving toxin concentrations. Environmental exposure distributions of microcystin concentrations were plotted and used to identify the likelihood of a given sample exceeding water guideline values as a function of regional geography, total phosphorus and chlorophyll-a concentration. This process identified regions with intensive cultivation and those most prone to water deficits associated with climate change to be most associated with exceedances of regulatory guideline values. Elevated phosphorus and chlorophyll-a concentrations were also drivers of toxin occurrence. This assessment can be used to identify water bodies of greatest risk to human and animal populations from cyanotoxins and thereby inform regulators as to most effective monitoring strategies.
{"title":"A probabilistic hazard assessment for cyanobacterial toxins accounting for regional geography and water body trophic status","authors":"Diane A. Mielewczyk , Chris N. Glover , Gavin N. Saari","doi":"10.1016/j.toxcx.2024.100208","DOIUrl":"10.1016/j.toxcx.2024.100208","url":null,"abstract":"<div><p>Under climate change scenarios freshwater eutrophication is expected to increase, and with it the occurrence of cyanobacterial toxin-producing harmful algal blooms. In the current study, microcystin toxin occurrence data from literature sources and a long-term provincial monitoring program were used to conduct a probabilistic hazard assessment for Alberta, Canada. The large temporal and spatial range of data makes Alberta a model system for identifying regional geography and water body trophic status factors driving toxin concentrations. Environmental exposure distributions of microcystin concentrations were plotted and used to identify the likelihood of a given sample exceeding water guideline values as a function of regional geography, total phosphorus and chlorophyll-a concentration. This process identified regions with intensive cultivation and those most prone to water deficits associated with climate change to be most associated with exceedances of regulatory guideline values. Elevated phosphorus and chlorophyll-a concentrations were also drivers of toxin occurrence. This assessment can be used to identify water bodies of greatest risk to human and animal populations from cyanotoxins and thereby inform regulators as to most effective monitoring strategies.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"24 ","pages":"Article 100208"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171024000250/pdfft?md5=1961cadfcb6242435fa5bac611f967ba&pid=1-s2.0-S2590171024000250-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142272916","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}
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.
{"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":"2024-12-01","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}
Pub Date : 2024-12-01Epub Date: 2024-09-19DOI: 10.1016/j.toxcx.2024.100209
David Meléndez-Martínez , Erika Ortega-Hernández , Edwin Estefan Reza-Zaldívar , Alejandro Carbajal-Saucedo , Gustavo Arnaud-Franco , Ana Gatica-Colima , Luis Fernando Plenge-Tellechea , Marilena Antunes-Ricardo , Daniel A. Jacobo-Velázquez , Karla Mayolo-Deloisa , Omar Lozano , Marco Rito-Palomares , Jorge Benavides
Animal venoms are natural products that have served as a source of novel molecules that have inspired novel drugs for several diseases, including for metabolic diseases such as type-2 diabetes and obesity. From venoms, toxins such as exendin-4 (Heloderma suspectum) and crotamine (Crotalus durissus terrificus) have demonstrated their potential as treatments for obesity. Moreover, other toxins such as Phospholipases A2 and Disintegrins have shown their potential to modulate insulin secretion in vitro. This suggests an unexplored diversity of venom peptides with a potential anti-obesogenic in Mexican rattlesnake venoms. For that reason, this study explored the in vitro effect of Crotalus venom peptide-rich fractions on models for insulin resistance, adipocyte lipid accumulation, antioxidant activity, and inflammation process through nitric oxide production inhibition. Our results demonstrated that the peptide-rich fractions of C. aquilus, C. ravus, and C. scutulatus scutulatus were capable of reverting insulin resistance, enhancing glucose consumption to normal control; C. culminatus, C. molossus oaxacus, and C. polystictus diminished the lipid accumulation on adipocytes by 20%; C. aquilus, C. ravus, and C. s. salvini had the most significant cellular antioxidant activity, having nearly 80% of ROS inhibition. C. aquilus, C. pyrrhus, and C. s. salvini inhibited nitric oxide production by about 85%. We demonstrated the potential of these peptides from Crotalus venoms to develop novel drugs to treat type-2 diabetes and obesity. Moreover, we described for the first time that Crotalus venom peptide fractions have antioxidant and inflammatory properties in vitro models.
{"title":"Bioprospection of rattlesnake venom peptide fractions with anti-adipose and anti-insulin resistance activity in vitro","authors":"David Meléndez-Martínez , Erika Ortega-Hernández , Edwin Estefan Reza-Zaldívar , Alejandro Carbajal-Saucedo , Gustavo Arnaud-Franco , Ana Gatica-Colima , Luis Fernando Plenge-Tellechea , Marilena Antunes-Ricardo , Daniel A. Jacobo-Velázquez , Karla Mayolo-Deloisa , Omar Lozano , Marco Rito-Palomares , Jorge Benavides","doi":"10.1016/j.toxcx.2024.100209","DOIUrl":"10.1016/j.toxcx.2024.100209","url":null,"abstract":"<div><div>Animal venoms are natural products that have served as a source of novel molecules that have inspired novel drugs for several diseases, including for metabolic diseases such as type-2 diabetes and obesity. From venoms, toxins such as exendin-4 (<em>Heloderma suspectum</em>) and crotamine (<em>Crotalus durissus terrificus</em>) have demonstrated their potential as treatments for obesity. Moreover, other toxins such as Phospholipases A<sub>2</sub> and Disintegrins have shown their potential to modulate insulin secretion in vitro. This suggests an unexplored diversity of venom peptides with a potential anti-obesogenic in Mexican rattlesnake venoms. For that reason, this study explored the in vitro effect of Crotalus venom peptide-rich fractions on models for insulin resistance, adipocyte lipid accumulation, antioxidant activity, and inflammation process through nitric oxide production inhibition. Our results demonstrated that the peptide-rich fractions of <em>C. aquilus, C. ravus</em>, and <em>C. scutulatus scutulatus</em> were capable of reverting insulin resistance, enhancing glucose consumption to normal control; <em>C. culminatus, C. molossus oaxacus</em>, and <em>C. polystictus</em> diminished the lipid accumulation on adipocytes by 20%; <em>C. aquilus, C. ravus</em>, and <em>C. s. salvini</em> had the most significant cellular antioxidant activity, having nearly 80% of ROS inhibition. <em>C. aquilus, C. pyrrhus,</em> and <em>C. s. salvini</em> inhibited nitric oxide production by about 85%. We demonstrated the potential of these peptides from <em>Crotalus</em> venoms to develop novel drugs to treat type-2 diabetes and obesity. Moreover, we described for the first time that <em>Crotalus</em> venom peptide fractions have antioxidant and inflammatory properties in vitro models.</div></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"24 ","pages":"Article 100209"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142417300","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 : 2024-12-01Epub Date: 2024-08-30DOI: 10.1016/j.toxcx.2024.100205
Jorge Vasconez-Gonzalez , Karen Delgado-Moreira , Esteban Gamez-Rivera , María Belen Lopez-Molina , Fredy Lizarazo Davila , Juan S. Izquierdo-Condoy , Esteban Ortiz-Prado
Approximately 1 million scorpion stings are recorded annually worldwide, resulting in 3000 deaths. Scorpion venom has various effects on the human body, with neurological complications occurring in about 2% of cases. Among these complications, stroke—whether ischemic or hemorrhagic—is particularly significant. A systematic literature review was conducted through a bibliographic search using key terms in the PubMed, Scopus, Scielo, Latin American and Caribbean Literature in Health Sciences (LILACS) and Google Schoolar databases without date restrictions. Articles related to stroke due to scorpion stings in Spanish, English, and Portuguese were included. Our protocol was registered in PROSPERO. A total of 24 articles met the inclusion criteria for this review. The primary neurological symptoms caused by scorpion stings include hemiplegia, hemiparesis, seizures, and limb weakness. Stroke should be suspected in the presence of these symptoms, as scorpion stings can lead to both hemorrhagic and ischemic strokes in both adults and pediatric populations. While stroke is a rare complication of scorpion stings, it is crucial to consider this diagnosis in patients presenting with neurological symptoms, necessitating the use of computed tomography or magnetic resonance imaging if stroke is suspected.
{"title":"Stroke as a rare complication of scorpion stings: A systematic review and analysis","authors":"Jorge Vasconez-Gonzalez , Karen Delgado-Moreira , Esteban Gamez-Rivera , María Belen Lopez-Molina , Fredy Lizarazo Davila , Juan S. Izquierdo-Condoy , Esteban Ortiz-Prado","doi":"10.1016/j.toxcx.2024.100205","DOIUrl":"10.1016/j.toxcx.2024.100205","url":null,"abstract":"<div><p>Approximately 1 million scorpion stings are recorded annually worldwide, resulting in 3000 deaths. Scorpion venom has various effects on the human body, with neurological complications occurring in about 2% of cases. Among these complications, stroke—whether ischemic or hemorrhagic—is particularly significant. A systematic literature review was conducted through a bibliographic search using key terms in the PubMed, Scopus, Scielo, Latin American and Caribbean Literature in Health Sciences (LILACS) and Google Schoolar databases without date restrictions. Articles related to stroke due to scorpion stings in Spanish, English, and Portuguese were included. Our protocol was registered in PROSPERO. A total of 24 articles met the inclusion criteria for this review. The primary neurological symptoms caused by scorpion stings include hemiplegia, hemiparesis, seizures, and limb weakness. Stroke should be suspected in the presence of these symptoms, as scorpion stings can lead to both hemorrhagic and ischemic strokes in both adults and pediatric populations. While stroke is a rare complication of scorpion stings, it is crucial to consider this diagnosis in patients presenting with neurological symptoms, necessitating the use of computed tomography or magnetic resonance imaging if stroke is suspected.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"24 ","pages":"Article 100205"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171024000225/pdfft?md5=179dfdf271603b577c9a070d3ce41e14&pid=1-s2.0-S2590171024000225-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142122586","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}
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