Amal Megdad-Lamraoui, Sonia Adi-Bessalem, Fares Daachi, Fatima Laraba-Djebari
{"title":"Proteasome-driven modulation of immune and oxidative pathways during scorpion envenomation pathogenesis.","authors":"Amal Megdad-Lamraoui, Sonia Adi-Bessalem, Fares Daachi, Fatima Laraba-Djebari","doi":"10.1590/1678-9199-JVATITD-2025-0007","DOIUrl":"10.1590/1678-9199-JVATITD-2025-0007","url":null,"abstract":"<p><strong>Background: </strong>Scorpion venom contains a variety of toxin molecules that are the drivers of inflammation and oxidative stress, leading to significant tissue damage. While several mechanisms underlying these responses have been studied, the involvement of the proteasome complex - a key regulator of inflammation - remains poorly understood. This study explored the role of the proteasome in modulating inflammatory and oxidative responses to envenomation by <i>Androctonus australis hector</i> venom.</p><p><strong>Methods: </strong>Mice were pretreated intraperitoneally with bortezomib, a proteasome inhibitor, at low (0.05 mg/kg), medium (0.25 mg/kg), or high (0.5 mg/kg) doses, 30 minutes prior to sublethal venom administration (0.5 mg/kg, subcutaneous). Twenty-four hours after venom administration, animals were euthanized, blood and organs were collected to evaluate vascular permeability (via Evans blue dye extravasation), the extent of inflammatory cell infiltration (myeloperoxidase and eosinophil peroxidase enzymatic activities), and oxidative/nitrosative stress markers (nitric oxide, hydrogen peroxide<sub>,</sub> malondialdehyde, catalase activity, and glutathione). Histopathological examinations were performed to identify structural alterations, such as edema, hemorrhage, and cellular infiltration. Biochemical parameters reflecting organ function, including serum levels of CPK, LDH, ALT, ALP, urea, and creatinine, were also measured to assess the degree of systemic damage.</p><p><strong>Results: </strong>Our findings revealed a dose-dependent immune-modulatory role of the proteasome system. A medium dose of bortezomib reduced inflammatory and oxidative stress markers, such as vascular permeability, eosinophil peroxidase, neutrophil peroxidase, nitric oxide, and malondialdehyde in renal tissue, suggesting a reduction in local inflammation and oxidative damage. In contrast, a higher dose showed pronounced preventive effects in cardiopulmonary and hepatic tissues, significantly reducing inflammatory mediators and oxidative markers, restoring antioxidant enzyme activity (catalase) and glutathione, as well as, improving tissue structure and organ function.</p><p><strong>Conclusion: </strong>These findings underscore the proteasome involvement in inflammatory regulation, likely through modulation of vascular permeability, immune cell activation, and oxidative stress, making it a key target in scorpion envenomation.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"31 ","pages":"e20250007"},"PeriodicalIF":1.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12431687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Haohao Wu, Lutao Xie, Wang Du, Linjie Lai, Peixin Shangguan, Xingzhen Wu, Jiefeng Xu, Pin Lan
{"title":"IMRC-Exo mitigates <i>Deinagkistrodon acutus</i> venom-induced limb injury in rabbits by inhibiting GSDME-dependent pyroptosis.","authors":"Haohao Wu, Lutao Xie, Wang Du, Linjie Lai, Peixin Shangguan, Xingzhen Wu, Jiefeng Xu, Pin Lan","doi":"10.1590/1678-9199-JVATITD-2025-0009","DOIUrl":"10.1590/1678-9199-JVATITD-2025-0009","url":null,"abstract":"<p><strong>Background: </strong>Inflammation plays a critical role in the pathogenesis of limb injury caused by <i>Deinagkistrodon acutus</i> snakebite. Investigating its regulatory mechanisms and intervention strategies may help identify effective treatments. Recent studies have shown that pyroptosis exacerbates organ damage by amplifying inflammatory responses. Additionally, immune and matrix-regulatory cells (IMRC), a novel type of mesenchymal stem cell, and their exosomes (Exo) have demonstrated potential in mitigating inflammation-mediated injury by suppressing pyroptosis. This study aimed to evaluate whether IMRC-Exo could alleviate <i>D. acutus</i> venom-induced limb injury in rabbits by suppressing pyroptosis, thereby attenuating the associated inflammatory response.</p><p><strong>Methods: </strong>Eighteen healthy male New Zealand white rabbits were randomly assigned to Sham, Model, and IMRC-Exo groups. The Model group was established by intramuscular injection of <i>D. acutus</i> venom (1.5 mg/kg), followed by intravenous snake antivenom (80 U/kg) after 2 hours. The IMRC-Exo group received IMRC-Exo (7.5 × 10<sup>10</sup> particles) post-modeling. Within 24 hours, left thigh circumference, serum creatine kinase (CK), and myoglobin (Mb) were assessed. Muscle tissues were collected for histopathology, apoptosis analysis, inflammatory cytokine quantification [high-mobility group box 1 (HMGB1), IL-1β, IL-18], and pyroptosis-related protein detection [caspase-3, cleaved caspase-3, gasdermin E (GSDME), N-terminal GSDME (N-GSDME)].</p><p><strong>Results: </strong>Compared to Sham, venom injection significantly increased thigh circumference, CK, Mb, histopathological damage, apoptosis, inflammatory cytokines, and pyroptosis-related proteins. IMRC-Exo significantly reduced these indicators, mitigating muscle injury and inflammation. Additionally, inflammatory cytokines and pyroptosis markers were significantly lower in the IMRC-Exo group than in the Model group.</p><p><strong>Conclusion: </strong>IMRC-Exo effectively alleviates <i>D. acutus</i> venom-induced limb injury in rabbits, likely through inhibition of GSDME-dependent pyroptosis-mediated inflammation. These findings suggest that IMRC-Exo may serve as a promising therapeutic approach for snakebite-induced inflammatory injury.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"31 ","pages":"e20230009"},"PeriodicalIF":1.8,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12412906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Phospholipase A<sub>2</sub> from <i>Daboia siamensis</i> venom induces acute kidney injury: involvement of ion channels in an isolated perfused rabbit kidney model.","authors":"Narongsak Chaiyabutr, Taksa Vasaruchapong, Panithi Laoungbua, Orawan Khow, Lawan Chanhome, Visith Sitprija","doi":"10.1590/1678-9199-JVATITD-2025-0016","DOIUrl":"10.1590/1678-9199-JVATITD-2025-0016","url":null,"abstract":"<p><strong>Background: </strong>Acute kidney injury (AKI) is a serious complication associated with <i>Daboia siamensis</i> envenomation, primarily due to direct nephrotoxicity. This study aimed to investigate the effects of the phospholipase A<sub>2</sub> (RvPLA₂) fraction from <i>D. siamensis</i> venom on renal function and to assess whether pretreatment with ion channel blockers could mitigate these effects using an isolated perfused kidney (IPK) model.</p><p><strong>Methods: </strong>Twenty IPKs were allocated into five groups (n = 4 each): (1) RvPLA₂ in calcium-deficient modified Krebs-Henseleit solution (MKHS), (2) RvPLA₂ in standard MKHS, (3) RvPLA₂ following pretreatment with verapamil (a voltage-gated Ca²⁺ channel blocker), (4) RvPLA₂ following pretreatment with amiloride (a Na⁺ channel blocker), and (5) RvPLA₂ following pretreatment with minoxidil (a KATP channel opener). Renal function parameters were assessed accordingly.</p><p><strong>Results: </strong>Administration of 280 μg of RvPLA₂ in calcium-deficient MKHS caused no significant changes in renal function. In contrast, RvPLA₂ in standard MKHS (1.9 mM Ca²⁺) significantly increased perfusion pressure (PP), renal vascular resistance (RVR), and free water excretion (<i>p</i> < 0.05), while non-significant increases were observed in glomerular filtration rate (GFR), urinary flow rate (UF), osmolar clearance (C<sub>osm</sub>), and the fractional excretion of sodium (FE<sub>Na⁺</sub>) and potassium (FE<sub>K⁺</sub>). Verapamil alone caused significant increases in GFR and C<sub>osm</sub> (<i>p</i> < 0.05) and non-significant increases in PP, RVR, UF, FE<sub>Na⁺</sub>, and free water excretion. Amiloride and minoxidil alone did not alter renal function. Pretreatment with verapamil, amiloride, or minoxidil failed to prevent the renal functional changes induced by RvPLA₂.</p><p><strong>Conclusions: </strong>The RvPLA<sub>2</sub> activity requires Ca<sup>2+</sup> for activation which may target distinct sites on the cell membrane, including ion channel receptors in nephrons. The effects of RvPLA<sub>2</sub> on glomerular and renal tubular function are independent and cannot be modified by pretreatment with different ion channel blockers.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"31 ","pages":"e20250016"},"PeriodicalIF":1.8,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiao-Qin Yu, Qi-Yun Zhang, Shu-Ting Zhou, Qing-Yu Lu, Qian-Yun Sun
{"title":"Promucetin, a new C-type lectin-like protein modulates coagulation by activating platelets via GPIb.","authors":"Xiao-Qin Yu, Qi-Yun Zhang, Shu-Ting Zhou, Qing-Yu Lu, Qian-Yun Sun","doi":"10.1590/1678-9199-JVATITD-2025-0003","DOIUrl":"10.1590/1678-9199-JVATITD-2025-0003","url":null,"abstract":"<p><strong>Background: </strong>Snake venom C-type lectin-like proteins (also known as snaclecs) have anticoagulation and procoagulation effects by targeting platelet or coagulation factor IX/X, suggesting their potential as candidates for new anticoagulant drugs. Therefore, this study aims to evaluate the antiplatelet and antithrombotic effects of a new snaclec from <i>Protobothrops mucrosquamatus</i> venom and its potential as an anticoagulant candidate.</p><p><strong>Methods: </strong>Promucetin was purified through sequential column chromatography, and its molecular mass was determined by SDS-PAGE. The α- and β-chains of promucetin were identified using liquid chromatography-mass spectrometry (LC-MS). <i>In vitro</i> analyses of platelet aggregation were performed using turbidimetric methods, thromboelastography, and coagulation activity assays. For <i>in vivo</i> experiments, promucetin was administered to rats at varying concentrations, and platelet changes were monitored. The antithrombotic effects of promucetin were assessed using a FeCl₃-induced rat thrombosis model.</p><p><strong>Results: </strong>Promucetin existed as two multimers with molecular weights of 140.1 kDa and 91.9 kDa under non-reducing conditions. Sequence analysis revealed that its α-chain and β-chain shared 71% and 34% homology, respectively, with TMVA from the same snake venom. <i>In vitro</i> platelet aggregation assays indicated that promucetin activated platelets via glycoprotein Ib. Thromboelastography showed that promucetin inhibited both coagulation factor activity and platelet function, resulting in an anticoagulant effect. Specifically, thrombin time was prolonged, while activated partial thromboplastin time and prothrombin time remained unchanged. <i>In vivo</i>, promucetin administration led to a dose-dependent decrease in platelet count. At doses of 25 and 50 μg/kg, promucetin significantly inhibited thrombosis, with inhibition rates of 40.9% and 74.4%, respectively. For comparison, lysine acetylsalicylate produced an inhibition rate of 36.7%.</p><p><strong>Conclusion: </strong>Promucetin exhibits significant ability to modulate coagulation function and effectively inhibit thrombosis by activating platelet via GPIb and reducing platelet count, which helps us understand its biological function in snake bites, it exhibits the potential to be a candidate for anticoagulant therapy.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"31 ","pages":"e20250003"},"PeriodicalIF":1.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12258407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yenny Yolanda Lozano Jiménez, Juan Daniel Hernández Vargas, David Mateo Navarrete Benavides, Ruth Mélida Sánchez Mora
{"title":"Use of spheroids as a model to evaluate the anticancer action of animal venoms and derived molecules: 2010-2024 review.","authors":"Yenny Yolanda Lozano Jiménez, Juan Daniel Hernández Vargas, David Mateo Navarrete Benavides, Ruth Mélida Sánchez Mora","doi":"10.1590/1678-9199-JVATITD-2024-0068","DOIUrl":"10.1590/1678-9199-JVATITD-2024-0068","url":null,"abstract":"<p><strong>Background: </strong>Cancer is one of the leading causes of death worldwide, with incidence rates continuously increasing, thereby posing a major healthcare challenge. Although many oncological drugs fulfill therapeutic requirements, they often show high toxicity due to their limited specificity. To address this problem, there has been a search for natural therapies, including animal venoms that harbor bioactive molecules with therapeutic potential, as well as biological models that facilitate their study. Consequently, three-dimensional culture models, such as spheroids, play a pivotal role in evaluating anticancer molecules, as they can effectively mimic <i>in vivo</i> tumor microenvironments.</p><p><strong>Methods: </strong>This study aimed to establish the significance of spheroids in identifying venom-derived molecules as potential therapeutic alternatives against cancer, based on a systematic review conducted from 2010 to 2024. Following PRISMA guidelines, a systematic search was conducted in four databases using the terms \"Spheroid\" and \"Venom\". Of the 93 articles identified, 16 satisfied the inclusion criteria for this review.</p><p><strong>Results: </strong>Notably, several bioactive molecules derived from snake, spider, scorpion, and bee venoms were evaluated using various spheroid formation methods. These molecules demonstrated cytotoxic effects that impaired spheroid formation and disrupted invasion and migration processes.</p><p><strong>Conclusion: </strong>Overall, the findings indicate that the integration of three-dimensional culture models with venom-derived compounds constitutes a promising preclinical strategy for the development of innovative, venom-based therapeutic strategies for cancer treatment.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"31 ","pages":"e20240068"},"PeriodicalIF":1.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rui Seabra Ferreira, Cristina Kampus Mantovani, Ana Silvia Sartori Barraviera Seabra Ferreira, Laura de Oliveira Nascimento, Merari de Fátima Ramires Ferrari, Daniel Fabio Kawano, Katlin Brauer Massirer, Gabriel Forato Anhê, Rosley Anholon, Celso Pereira Caricati, Luciane Meneguin Ortega, Sarah Guilbert, Teresa Lambe, José Paes Oliveira-Filho, Sue Ann Costa Clemens, Benedito Barraviera
{"title":"Translational science at the undergraduate level: awakening talents to overcome the valley of death - case report.","authors":"Rui Seabra Ferreira, Cristina Kampus Mantovani, Ana Silvia Sartori Barraviera Seabra Ferreira, Laura de Oliveira Nascimento, Merari de Fátima Ramires Ferrari, Daniel Fabio Kawano, Katlin Brauer Massirer, Gabriel Forato Anhê, Rosley Anholon, Celso Pereira Caricati, Luciane Meneguin Ortega, Sarah Guilbert, Teresa Lambe, José Paes Oliveira-Filho, Sue Ann Costa Clemens, Benedito Barraviera","doi":"10.1590/1678-9199-JVATITD-2025-0005","DOIUrl":"10.1590/1678-9199-JVATITD-2025-0005","url":null,"abstract":"<p><strong>Background: </strong>In the biomedical field, translational science is the process of applying basic scientific knowledge to advance clinical research through the creation of new drugs, devices, medical procedures, preventive measures, and diagnostic kits. The Covid-19 pandemic exposed a shortage of professionals trained in translational research, essential for responding to global demands. To drive advancements, researchers must overcome the 'valley of death', a critical phase in clinical investigation. In response, CEVAP at São Paulo State University (UNESP), Botucatu, Brazil, has developed a strong 'knowledge industry' centered on Translational Science. As part of its research and innovation efforts, CEVAP has developed two biopharmaceuticals, the fibrin sealant and the apilic antivenom, which are currently in the final stage of development. In 2024, CEVAP began the first Brazilian Contract Development and Manufacturing Organization (CDMO) for developing and producing validated and qualified pilot-scale batches to generate clinical trial material.</p><p><strong>Case presentation: </strong>The implementation of the optional undergraduate course in Translational Science marks a crucial step in strengthening the 'knowledge industry'. The program, developed in collaboration with São Paulo's three public universities (USP, UNESP, and UNICAMP), also involves an international partnership with the University of Oxford's Department of Pediatrics and the Oxford Research Group LATAM. The successful launch of this course underscores its importance in interdisciplinary education and institutional collaboration. By bridging gaps between research and application, the program equips professionals to meet the growing demand for expertise in translational science. Given the project's success, it will transition into a one-year 'Qualification in Translational Science', available to students enrolled in São Paulo state universities.</p><p><strong>Conclusion: </strong>The preparation of these professionals will be strategic for transforming basic research into products for health, saving lives, and combating future pandemics that will emerge around the world.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"31 ","pages":"e20250005"},"PeriodicalIF":1.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mônica Lopes-Ferreira, Felipe Justiniano Pinto, Yasmin Stefanie Oliveira Costa, Alessa Aparecida Burgarelli, Louise Lene Gomes Lima, Bibiana da Silva Marques, Carla Simone Seibert, Elineide Eugenio Marques, Patrícia Charvet, Vidal Haddad, João Gabriel Dos Santos Rosa, Geonildo Rodrigo Disner, Carla Lima
{"title":"A comprehensive overview of fish envenomation and venom toxicity in Brazil.","authors":"Mônica Lopes-Ferreira, Felipe Justiniano Pinto, Yasmin Stefanie Oliveira Costa, Alessa Aparecida Burgarelli, Louise Lene Gomes Lima, Bibiana da Silva Marques, Carla Simone Seibert, Elineide Eugenio Marques, Patrícia Charvet, Vidal Haddad, João Gabriel Dos Santos Rosa, Geonildo Rodrigo Disner, Carla Lima","doi":"10.1590/1678-9199-JVATITD-2024-0061","DOIUrl":"10.1590/1678-9199-JVATITD-2024-0061","url":null,"abstract":"<p><strong>Background: </strong>Brazilian waters are home to various venomous fish species, each with its unique venom composition. Although common, envenomation cases are largely underreported, leading to a lack of public health policies for prevention and treatment. Some of the most clinically relevant fish in Brazil include the stingray <i>Potamotrygon orbignyi</i>, the toadfish <i>Thalassophryne nattereri</i>, the scorpionfish <i>Scorpaena plumieri</i>, and the catfish <i>Pseudoplatystoma fasciatum</i> and <i>Cathorops spixii</i>.</p><p><strong>Methods: </strong>We comprehensively searched reports about accidents involving venomous fish in Brazil and compared the toxic activities of some medically relevant species.</p><p><strong>Results: </strong>From the biochemical and toxicological evaluation, we found that venoms show a hierarchy in the ability to induce local toxic effects in mice, probably related to the venom compound diversity with species-specific toxins. <i>T. nattereri</i> venom presents greater toxicity, causing more severe local responses than that of <i>P. orbignyi</i>, <i>C. spixii</i>, and <i>P. fasciatum</i>, which cause moderate reactions. The <i>S. plumieri</i> venom induced only a moderate level of edema and could not cause nociception or necrosis. These results highlight that envenomation by <i>P. orbigny</i>, <i>C. spixii</i>, and <i>S. plumieri</i> is marked by proteins with intense hemolytic/proteolytic and phospholipase activity. On the other hand, <i>T. nattereri</i> and <i>P. fasciatum</i> offered a broader panel of new toxin families.</p><p><strong>Conclusion: </strong>Knowledge of fish venom biochemical and toxicological activities is crucial to antivenom therapy development and helps endorse the study of venomous fish and their impact on the public health system.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"31 ","pages":"e20240061"},"PeriodicalIF":1.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12088643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elcio Daniel Sousa Barros, Evaldo Dos Santos Monção, Mariana Helena Chaves, Cícero Alves Lopes, Gerardo Magela Vieira
{"title":"Development and validation of a spectrophotometric method for the quantification of total bufadienolides in samples of toad glandular secretions.","authors":"Elcio Daniel Sousa Barros, Evaldo Dos Santos Monção, Mariana Helena Chaves, Cícero Alves Lopes, Gerardo Magela Vieira","doi":"10.1590/1678-9199-JVATITD-2024-0064","DOIUrl":"10.1590/1678-9199-JVATITD-2024-0064","url":null,"abstract":"<p><strong>Background: </strong>Bufadienolides are the main secondary metabolites found in the paratoid gland secretions (PGS) of toads of the Bufonidae family. These compounds are considered the main bioactive components of PGS. The aim of this study was to develop and validate the first method for the quantification of total bufadienolides (free and esterified) in samples of paratoid secretions from toads, using the UV-Vis absorption spectrophotometry technique.</p><p><strong>Methods: </strong>The proposed method was based on the bathochromic shift induced by the reaction of the α-pyrone group of bufadienolides (296 nm) with a 5% (w:v) aqueous solution of sodium hydroxide and detection at 356 nm, after 60 min (time defined based on the evaluation of kinetic assays).</p><p><strong>Results: </strong>The proposed method showed wide linearity (r = 0.9999), low LOD (1.3 × 10<sup>-4</sup> µg/mL) and LOQ (3.9 × 10<sup>-4</sup> µg/mL), recovery (84%-99%), repeatability (%RSD ≤ 5), reproducibility and robustness (p > 0.05). The total bufadienolide content in PGS extracts from 12 samples of <i>R. diptycha</i> ranged from 478 to 801 mg of EqMB/g of extract, while the <i>R. granulosa</i> sample presented 661 mg of EqMB/g of extract.</p><p><strong>Conclusion: </strong>The new developed method is innovative, simple, fast, accurate, robust, low cost, and can contribute to future research focused on the quantification of total bufadienolides in samples of toad glandular secretions. In addition to serving as a strategic tool in the selection of work matrices, optimizing time, and minimizing costs.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"31 ","pages":"e20240064"},"PeriodicalIF":1.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Haiting Zhu, Yuexin Pan, Zhiyuan Tai, Mingqian Wang, Xia Liu, Xiaodong Yu, Qiyi He
{"title":"Epitope-based antibody development against metalloproteinases and phospholipases A<sub>2</sub> from <i>Deinagkistrodon acutus</i> venom.","authors":"Haiting Zhu, Yuexin Pan, Zhiyuan Tai, Mingqian Wang, Xia Liu, Xiaodong Yu, Qiyi He","doi":"10.1590/1678-9199-JVATITD-2024-0060","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2024-0060","url":null,"abstract":"<p><strong>Background: </strong><i>Deinagkistrodon acutus</i>, or the hundred-pace snake, poses severe health risks due to its venom. Envenomation by this snake leads to complications such as hemorrhage, edema, and coagulopathy. Traditional antivenoms are limited by venom variability and often contain non-neutralizing antibodies, highlighting the need for more precise and effective immunogens.</p><p><strong>Methods: </strong>This study utilized epitope-based antibody technology to develop a targeted sera against venom metalloproteinases (MPs) and phospholipases A<sub>2</sub> (PLA<sub>2</sub>s). Twelve antigenic epitopes were identified via bioinformatics, leading to the design of a composite antigen peptide, EpiMPLA. It was engineered to be expressed via two expression systems, resulting in the recombinant immunogens, ProMPLA and p2AMPLA.</p><p><strong>Results: </strong>Immunization with ProMPLA and p2AMPLA produced robust antibody responses in mice, effectively inhibiting MPs and PLA<sub>2</sub>s. <i>In vitro</i> assays demonstrated that sera from immunized mice reduced the activity of these venom enzymes, minimized venom-induced hemorrhage and edema, and restored blood coagulation. At a venom dose of 2×LD<sub>50</sub>, all mice in the control group died, while survival rates were 90% for anti-ProMPLA and 70% for anti-p2AMPLA.</p><p><strong>Conclusion: </strong>The EpiMPLA epitope represents a promising candidate for generating neutralizing antibodies against <i>D. acutus</i>venom, demonstrating its potential to address critical gaps in current antivenom therapy. These findings not only validate the feasibility of epitope-based antivenom development but also pave the way for further research to optimize this strategy.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"31 ","pages":"e20240060"},"PeriodicalIF":1.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12063738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Giovana Pedro, Felipe César da Silva Brasileiro, Rui Seabra Ferreira, Aline Márcia Marques Bráz, Renée Laufer-Amorim
{"title":"Melittin inhibits proliferation, migration, and invasion in osteosarcoma cell lines using 2D and 3D models.","authors":"Giovana Pedro, Felipe César da Silva Brasileiro, Rui Seabra Ferreira, Aline Márcia Marques Bráz, Renée Laufer-Amorim","doi":"10.1590/1678-9199-JVATITD-2024-0053","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2024-0053","url":null,"abstract":"<p><strong>Background: </strong>Osteosarcoma is the most common primary bone tumor in humans. It is a locally aggressive tumor at the primary site, with metastasis being the main cause of death in patients. Studies on dogs have gained prominence in oncology, as they are valuable spontaneous models of osteosarcoma. In the context of natural compounds, biotoxins are attracting increasing research interest as new therapeutic agents against cancer, such as melittin, that represents 40 to 50% of the dry weight of bee venom, and studies have already shown its antitumor effects.</p><p><strong>Methods: </strong>We analyzed the anti-migratory and anti-invasive potential of melittin, with the wound healing and Transwell tests, apoptosis with Annexin V/IP and cell viability with the MTT test in 2D and 3D models.</p><p><strong>Results: </strong>Melittin had a cytotoxic effect on osteosarcoma cell lines, with an IC50 between 1.5 and 2.5 µg/mL. In the wound healing test and Transwell test, melittin prevented cell migration and invasion, resulting in cell death due to iodide propidium marking in canine, murine and human cell lines. Melittin exhibited cytotoxicity in a 3D model of osteospheres, with a significantly higher IC50 in this type of culture, with values between 3.5 and 4.0 µg/mL.</p><p><strong>Conclusion: </strong>We conclude that melittin has antitumor and antimetastatic properties in canine, murine and human osteosarcoma cell lines. Consequently, we believe that further research on this promising compound will facilitate its application in the development of therapeutic agents for osteosarcoma, ultimately contributing to improved survival outcomes for cancer patients.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"31 ","pages":"e20240053"},"PeriodicalIF":1.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11996085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}