Toxicon: X最新文献

{"title":"Drugs from poisonous plants: Ethnopharmacological relevance to modern perspectives","authors":"Bhagya Lakhmi Rajbongshi ,&nbsp;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}

{"title":"Feasibility study: Varespladib protects CD-1 mice from lethal doses of whole bee (Apis mellifera) venom","authors":"James Hearth ,&nbsp;Kaitlin Linne ,&nbsp;Jerry Harrison ,&nbsp;Hossein Zolfaghari ,&nbsp;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 χ² = 8.29; p &lt; 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}

{"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,&nbsp;Gina Durán,&nbsp;Maykel Cerdas,&nbsp;Jairo Gutiérrez,&nbsp;Álvaro Segura,&nbsp;María Herrera,&nbsp;Mariángela Vargas,&nbsp;Adriana Sánchez,&nbsp;Paola Sánchez,&nbsp;Gabriela Solano,&nbsp;Mauren Villalta,&nbsp;Edwin Moscoso,&nbsp;Deibid Umaña,&nbsp;Mauricio Arguedas,&nbsp;Aarón Gómez,&nbsp;José María Gutiérrez,&nbsp;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}

{"title":"Stress levels, hematological condition, and productivity of plasma-producing horses used for snake antivenom manufacture: A comparison of two industrial bleeding methods","authors":"Ana Margarita Arias-Esquivel ,&nbsp;Edwin Moscoso ,&nbsp;Deibid Umaña ,&nbsp;Mauricio Arguedas ,&nbsp;Daniela Solano ,&nbsp;Gina Durán ,&nbsp;Aarón Gómez ,&nbsp;José María Gutiérrez ,&nbsp;Guillermo León","doi":"10.1016/j.toxcx.2024.100212","DOIUrl":"10.1016/j.toxcx.2024.100212","url":null,"abstract":"<div><div>The immunization and industrial bleeding of horses are essential stages for producing snake antivenoms. In Costa Rica, the traditional method involves stimulating the antibody response of horses by periodically injecting venoms, collecting hyperimmune plasma over three consecutive bleeding days, and repeating this process every eight weeks. While this method does not cause major physical or hematological issues in horses, the associated stress has not been evaluated. We compared this traditional method with an alternative method that involves injecting venoms, collecting hyperimmune plasma in a single bleeding day, and repeating the process every two weeks. We assessed stress (via serum and fecal cortisol levels and an ethological study), hematological parameters (hematocrit and hemoglobin concentration), and plasma productivity over eight months. Serum cortisol levels remained within the normal range for both methods throughout the immunization/bleeding cycle. However, serum and fecal cortisol levels were significantly higher in horses subjected to the traditional method compared to those in the alternative method. Neither method caused significant hematological alterations. Notably, the alternative method yielded a higher volume of plasma. We concluded that adopting the alternative method ensures horse welfare while improving industrial bleeding productivity. This approach may reduce costs and improve the availability of this essential treatment for vulnerable populations.</div></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"24 ","pages":"Article 100212"},"PeriodicalIF":3.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142535278","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}

{"title":"Diagnosis of human envenoming by terrestrial venomous animals: Routine, advances, and perspectives","authors":"Joeliton S. Cavalcante ,&nbsp;Sabrina Santana Toledo Arruda ,&nbsp;Pedro Marques Riciopo ,&nbsp;Manuela Pucca ,&nbsp;Rui Seabra Ferreira Junior","doi":"10.1016/j.toxcx.2024.100211","DOIUrl":"10.1016/j.toxcx.2024.100211","url":null,"abstract":"<div><div>Despite the development of new and advanced diagnostic approaches, monitoring the clinical evolution of accidents caused by venomous animals is still a challenge for science. In this review, we present the state of the art of laboratory tests that are routinely used for the diagnosis and monitoring of envenomings by venomous animals, as well as the use of new tools for more accurate and specific diagnoses. While a comprehensive range of tools is outlined, comprising hematological, biochemical, immunoassays, and diagnostic imaging tools, it is important to acknowledge their limitations in predicting the onset of clinical complications, since they provide an overview of organic damage after its development. Thus, the need for discovery, validation, and use of biomarkers that have greater predictive power, sensitivity and specificity is evident. This will help in the diagnosis, monitoring, and treatment of patients envenomated by venomous animals, consequently reducing the global burden of morbidity and mortality.</div></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"24 ","pages":"Article 100211"},"PeriodicalIF":3.6,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142535313","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}

{"title":"Supplementation of polyclonal antibodies, developed against epitope-string toxin-specific peptide immunogens, to commercial polyvalent antivenom, shows improved neutralization of Indian Big Four and Naja kaouthia snake venoms","authors":"Abhishek Chanda ,&nbsp;Nitin C. Salvi ,&nbsp;Pravin V. Shelke ,&nbsp;Bhargab Kalita ,&nbsp;Aparup Patra ,&nbsp;Upasana Puzari ,&nbsp;Milind V. Khadilkar ,&nbsp;Ashis K. Mukherjee","doi":"10.1016/j.toxcx.2024.100210","DOIUrl":"10.1016/j.toxcx.2024.100210","url":null,"abstract":"<div><div>Snakebites profoundly impact the rural population of tropical nations, leading to significant socio-economic repercussions. Polyvalent antivenom (PAV) therapy faces several limitations, including intra-specific variations and poor efficacy against some major toxins and low molecular mass, poorly immunogenic toxins, which contribute to increased mortality and morbidity rates. Innovative strategies for developing novel antivenoms are continuously explored to address these challenges. The present study focuses on designing of 17 epitope-string toxin-specific peptide immunogens from pharmacologically active major and/or poorly immunogenic toxins (snake venom metalloprotease, Kunitz-type serine protease inhibitor, phospholipase A₂, three-finger toxin) from the venom of the ‘Big Four’ venomous snakes and <em>Naja kaouthia</em> (NK) in India. These custom peptide antibodies demonstrated robust immuno-reactivity against the venoms ‘Big Four’ and NK. When these antibodies were supplemented with commercial PAV at a defined ratio (formulated polyvalent antivenom or FPAV), it significantly enhanced the neutralization of snake venom enzymes and <em>in vivo</em> neutralization of lethality and pharmacological activities such as haemorrhage, necrosis, pro-coagulant, defibrinogenation, and myotoxicity of ‘Big Four’ and NK venoms compared to PAV in mice. The present study highlights a promising strategy for developing next-generation antivenoms using synthetic peptide-based immunogens, offering a targeted approach to address the limitations of current antivenom therapy.</div></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"24 ","pages":"Article 100210"},"PeriodicalIF":3.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142417299","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}

{"title":"Bioprospection of rattlesnake venom peptide fractions with anti-adipose and anti-insulin resistance activity in vitro","authors":"David Meléndez-Martínez ,&nbsp;Erika Ortega-Hernández ,&nbsp;Edwin Estefan Reza-Zaldívar ,&nbsp;Alejandro Carbajal-Saucedo ,&nbsp;Gustavo Arnaud-Franco ,&nbsp;Ana Gatica-Colima ,&nbsp;Luis Fernando Plenge-Tellechea ,&nbsp;Marilena Antunes-Ricardo ,&nbsp;Daniel A. Jacobo-Velázquez ,&nbsp;Karla Mayolo-Deloisa ,&nbsp;Omar Lozano ,&nbsp;Marco Rito-Palomares ,&nbsp;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 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 <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":"2024-09-19","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}

{"title":"A probabilistic hazard assessment for cyanobacterial toxins accounting for regional geography and water body trophic status","authors":"Diane A. Mielewczyk ,&nbsp;Chris N. Glover ,&nbsp;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":"2024-09-16","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}

{"title":"Plug and play virus-like particles for the generation of anti-toxin antibodies","authors":"Rebecca J. Edge ,&nbsp;Amy E. Marriott ,&nbsp;Emma L. Stars ,&nbsp;Rohit N. Patel ,&nbsp;Mark C. Wilkinson ,&nbsp;Lloyd D.W. King ,&nbsp;Julien Slagboom ,&nbsp;Choo Hock Tan ,&nbsp;Kavi Ratanabanangkoon ,&nbsp;Simon J. Draper ,&nbsp;Stuart Ainsworth","doi":"10.1016/j.toxcx.2024.100204","DOIUrl":"10.1016/j.toxcx.2024.100204","url":null,"abstract":"<div><p>Snakebite is a major global health concern, for which antivenom remains the only approved treatment to neutralise the harmful effects of the toxins. However, some medically important toxins are poorly immunogenic, resulting in reduced efficacy of the final product. Boosting the immunogenicity of these toxins in the commercial antivenom immunising mixtures could be an effective strategy to improve the final dose efficacy, and displaying snake antigens on Virus-like particles (VLPs) is one method for this. However, despite some applications in the field of snakebite, VLPs have yet to be explored in methods that could be practical at an antivenom manufacturing scale. Here we describe the utilisation of a “plug and play” VLP system to display immunogenic linear peptide epitopes from three finger toxins (3FTxs) and generate anti-toxin antibodies. Rabbits were immunised with VLPs displaying individual consensus linear epitopes and their antibody responses were characterised by immunoassay. Of the three experimental consensus sequences, two produced antibodies capable of recognising the consensus peptides, whilst only one of these could also recognise native whole toxins. Further characterisation of antibodies raised against this peptide demonstrated a sub-class specific response, and that these were able to elicit partially neutralising antibody responses, resulting in increased survival times in a murine snakebite envenoming model.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"23 ","pages":"Article 100204"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171024000213/pdfft?md5=ba01fce4aaed7e7545df55c4bc9a9c0d&pid=1-s2.0-S2590171024000213-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142099558","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}

{"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,&nbsp;Edwin Moscoso,&nbsp;Deibid Umaña,&nbsp;Mariángela Vargas,&nbsp;Andrés Sánchez,&nbsp;Andrés Hernández,&nbsp;Gina Durán,&nbsp;Mauren Villalta,&nbsp;Aarón Gómez,&nbsp;María Herrera,&nbsp;Mauricio Arguedas,&nbsp;José María Gutiérrez,&nbsp;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":"2024-08-30","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}