Toxicon最新文献

{"title":"Barietin, a snake venom vascular endothelial growth factor from puff adder Bitis arietans venom, increases the heart rate with minor effect on blood pressure in rats.","authors":"Maria S Severyukhina, Alexey V Osipov, Alina M Ismailova, Elvira R Shaykhutdinova, Igor A Dyachenko, Vladislav G Starkov, Rustam H Ziganshin, Nikita D Timofeev, Arkady N Murashev, Victor I Tsetlin, Yuri N Utkin","doi":"10.1016/j.toxicon.2026.109275","DOIUrl":"10.1016/j.toxicon.2026.109275","url":null,"abstract":"<p><p>Snake venom vascular endothelial growth factors (svVEGFs) are homodimeric proteins comprising two equal subunits bound by two intermolecular disulfide bonds. The main biological effects of svVEGFs are local vasodilatation, increasing of vascular permeability, and hypotension. Barietin, a svVEGF purified from the venom of puff adder Bitis arietans, differs from other representatives of this toxin family by its shortened C-terminal amino acid sequence. No data about barietin effects on hemodynamics are available. Studying those in rats we found that barietin at a dose of 1 mg/kg significantly increased heart rate, exerting only a minor influence on blood pressure. In this respect, it differs from other svVEGFs having a significant effect on blood pressure. We aimed to find the barietin active fragment which may be responsible for its tachycardic activity. Because in literature the fragments corresponding to the so-called loop 1 of VEGF-A (a mammalian homologue of barietin) manifested some affinity to VEGF receptors, we synthesized a peptide homologous to this loop comprising barietin fragment 24-36, with two Cys residues added at the N- and C-termini to form a disulfide. At intravenous injection at a dose of 5 mg/kg, it showed a tendency to increase heart rate without any significant effect on blood pressure, thus demonstrated a trend to reproduce the effect of barietin. So, barietin is the first svVEGF which increases the heart rate without substantial effect on the blood pressure, with its fragment demonstrating a trend for a similar activity.</p>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":" ","pages":"109275"},"PeriodicalIF":2.8,"publicationDate":"2026-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148819736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From policy statement to the village clinic: closing the snakebite care gap in rural Nigeria.","authors":"Godpower Chinedu Michael, Ason Benjamin Tsuung, Lukman Abolaji Mohammed","doi":"10.1016/j.toxicon.2026.109337","DOIUrl":"https://doi.org/10.1016/j.toxicon.2026.109337","url":null,"abstract":"","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":" ","pages":"109337"},"PeriodicalIF":2.8,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mycotoxin-induced DNA damage response and its association with carcinogenesis.","authors":"Priyanka Singh, Ravindranath S Bilachi, Prakash Peralam Yegneswaran, Depanshi Pandit, Manash K Paul","doi":"10.1016/j.toxicon.2026.109313","DOIUrl":"10.1016/j.toxicon.2026.109313","url":null,"abstract":"<p><p>Fungal species produce various secondary metabolites with carcinogenic and genotoxic properties, including aflatoxins, ochratoxins, fumonisins, sterigmatocystin, and griseofulvin. Acute or chronic exposure to these mycotoxins through contaminated food and feed can cause DNA damage, chromosomal instability, and epigenetic changes, ultimately leading to cancer. This review focuses on IARC-classified carcinogenic mycotoxins and their contribution to cancer development by disrupting the DNA damage response (DDR), thereby affecting apoptosis, cell cycle regulation, and genomic stability. Current knowledge of co-exposure to mycotoxins, host susceptibility, and validated biomarkers remains limited, particularly regarding the regulation of DDR genes. This necessitates more in-depth mechanistic and epidemiological research. Network analysis of host genes associated with mycotoxins in the CTD, integrated with DDR-related genes curated from CancerSEA, identified candidate DDR-associated genes implicated in pathways related to cell cycle regulation, DNA repair, oxidative stress response, and apoptosis. These findings represent database-derived associations and computational prioritization, rather than evidence of causal mechanistic roles in mycotoxin-induced carcinogenesis. Enrichment analysis using the Enrichr tool further identified the association between mycotoxin-associated DDR genes and cancer. In brief, this review enhances the understanding of the role of mycotoxins in DDR mechanisms and their potential contribution to cancer development, thereby providing a basis for improved molecular and translational approaches to address the associated health risks.</p>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":" ","pages":"109313"},"PeriodicalIF":2.8,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149196882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroactive mini-M conotoxins in Conus tessulatus.","authors":"Charmaine B Mendoza, Zildjian G Acyatan, Ella Mae E Gamba, Baldomero M Olivera, Eizadora T Yu, Gisela P Concepcion, Arturo O Lluisma, Lilibeth Salvador-Reyes","doi":"10.1016/j.toxicon.2026.109322","DOIUrl":"https://doi.org/10.1016/j.toxicon.2026.109322","url":null,"abstract":"<p><p>Two small peptides were purified from the venom of the vermivorous cone snail, Conus tessulatus, and evaluated for neuroactivity. Structural characterization by Edman sequencing and mass spectrometry revealed that the two peptides, named ts3b and ts3c, are 14 amino acids long and can be classified as mini-M conotoxins under framework III, M-superfamily, M2 branch. Native samples of ts3b and ts3c caused temporary swimming paralysis in fish, yet elicited distinct responses in the dorsal root ganglion (DRG) assay and the Constellation Pharmacology platform. Peptide ts3b caused mild sluggishness and shaking in young mice and irreversible, indirect excitation in a primary culture of DRG neurons. Furthermore, nanomolar concentration of native ts3b affected small diameter peptidergic nociceptors (PNs) and c-low threshold mechanoreceptors (C-LTMRs) in the DRG. Interestingly, ts3c caused an irreversible block in cultured DRG neurons, primarily affecting capsaicin-sensitive PN cells and capsaicin-insensitive non-peptidergic nociceptors (NPNs). The bioactivities suggest that ts3b and ts3c may target distinct ion channels or receptors. Two ts3b toxiforms were also identified as ts3b Asn15 toxiform and ts3b Ser7Arg, Asn15 toxiform. The toxiforms have a similar loop pattern, post-translational modifications, and cysteine framework with ts3b. Native ts3b and the toxiforms caused mild lethargy in mice. Peptide ts3b and ts3c are the first neuroactive mini-M conotoxins described from C. tessulatus. Few neuroactive conotoxins have been reported under the M-2 branch, and these compounds may have novel molecular and pharmacological targets due to their diverse structural conformations.</p>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":" ","pages":"109322"},"PeriodicalIF":2.8,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reporting the neutralization capacity of recombinant antivenoms: mass dose or molar dose?","authors":"Anne Ljungars, Andreas H Laustsen","doi":"10.1016/j.toxicon.2026.109270","DOIUrl":"10.1016/j.toxicon.2026.109270","url":null,"abstract":"","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":" ","pages":"109270"},"PeriodicalIF":2.8,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148764902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"When tarantula venom comes from a misnamed spider: The importance of taxonomic accuracy in theraphosid toxinology.","authors":"Luis A Roque","doi":"10.1016/j.toxicon.2026.109262","DOIUrl":"10.1016/j.toxicon.2026.109262","url":null,"abstract":"","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":" ","pages":"109262"},"PeriodicalIF":2.8,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148761720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rafael Otero Patiño (1946-2026).","authors":"José María Gutiérrez","doi":"10.1016/j.toxicon.2026.109201","DOIUrl":"https://doi.org/10.1016/j.toxicon.2026.109201","url":null,"abstract":"","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":" ","pages":"109201"},"PeriodicalIF":2.8,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148284427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of GCN2/eIF2α signaling pathway in MC-LR-induced hepatocyte oxidative damage and alpha-lipoic acid intervention","authors":"Ailin Tan ,&nbsp;Yu Huang ,&nbsp;Hanyun Shen ,&nbsp;Chaoyun Chen ,&nbsp;Qingbi Zhang ,&nbsp;Jun Bai ,&nbsp;Liangping Luo ,&nbsp;Xuelian Jiang ,&nbsp;Shuai Li ,&nbsp;Zhixia Han","doi":"10.1016/j.toxicon.2026.109020","DOIUrl":"10.1016/j.toxicon.2026.109020","url":null,"abstract":"<div><div>Prior research indicates that α-lipoic acid (α-LA) confers protection against the hepatotoxic effects of microcystin-LR (MC-LR), although the precise mechanisms remain to be fully defined. This investigation aims to elucidate how the reactive oxygen species (ROS)-mediated GCN2/eIF2α pathway enables α-LA to mitigate oxidative damage in hepatocytes caused by MC-LR, thus providing a robust scientific foundation for elucidating the mechanisms of MC-LR-induced cellular damage and identifying novel preventive and therapeutic approaches. For this purpose, human normal hepatocytes (L02 cells) and mouse normal hepatocytes (AML12 cells) were categorized into ten experimental groups: a blank control group, a 1 μM MC-LR exposure group, a 50 μg/mL α-LA group, combined MC-LR and α-LA groups, an siGCN2 group, a GCN2 inhibitor (GCN2iB) group, and groups treated with 1 μM MC-LR in conjunction with siGCN2 or GCN2iB. The investigation revealed that MC-LR diminishes SOD activity, elevates MDA levels, reduces mitochondrial membrane potential, and stimulates ROS generation, culminating in oxidative cellular damage. MC-LR activates the GCN2/eIF2α pathway by promoting ROS, resulting in oxidative damage to cells. Furthermore, application of inhibitors or silencing of GCN2 activity can reduce ROS generation, thereby attenuating MC-LR-induced oxidative damage in hepatocytes. α-LA pretreatment enhances the antioxidant capacity of AML12 cells and L02 cells and alleviates MC-LR-induced oxidative stress (OS). It is suggested that α-LA can protect AML12 cells and L02 cells from oxidative damage caused by MC-LR to a certain extent. α-LA can alleviate MC-LR-induced oxidative damage in AML12 and L02 cells to a certain extent by inhibiting the GCN2/eIF2α pathway.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"274 ","pages":"Article 109020"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146182619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severe venom-induced consumption coagulopathy, snakebite-associated thrombotic microangiopathy, and local necrosis following Western bush viper (Atheris chlorechis) envenoming in France","authors":"Sébastien Larréché ,&nbsp;Gael Le Roux ,&nbsp;Jean-Philippe Chippaux ,&nbsp;Jérémy Hardy ,&nbsp;Anne-Laure Fédou ,&nbsp;Magali Labadie","doi":"10.1016/j.toxicon.2026.109021","DOIUrl":"10.1016/j.toxicon.2026.109021","url":null,"abstract":"<div><h3>Background</h3><div><em>Atheris</em> spp. are small African vipers whose bites are rarely reported but can result in significant envenoming. There is no specific antivenom available. We describe a case of systemic <em>A. chlorechis</em> envenoming presenting with venom-induced consumption coagulopathy (VICC), snakebite-associated thrombotic microangiopathy (TMA), and local necrosis.</div></div><div><h3>Case presentation</h3><div>A 33-year-old man was bitten on the index finger by a captive <em>A. chlorechis</em>. Within 6 hours, early laboratory abnormalities progressed to VICC with markedly prolonged PT/aPTT, undetectable fibrinogen, elevated fibrin monomers, and factor V deficiency. Despite the administration of four vials of Inoserp™ Pan-Africa and repeated transfusions of fibrinogen and fresh frozen plasma, the patient continued to exhibit signs of coagulopathy for 48 hours. Thrombocytopenia, anaemia, schistocytes, and hyperbilirubinemia indicated snakebite-associated TMA, which resolved spontaneously without renal involvement. Progressive local necrosis developed on the finger and dorsal hand, ultimately requiring amputation of the proximal phalanx and surgical debridement.</div></div><div><h3>Conclusion</h3><div>This case demonstrates that <em>A. chlorechis</em> envenoming can produce both local and systemic toxicity. The absence of clinical improvement after Inoserp™ Pan-Africa is consistent with preclinical data showing limited cross-neutralization against <em>Atheris</em> venoms. Administration of clotting factors in the presence of unneutralized procoagulant toxins may have contributed to the development of TMA. Therefore, fresh frozen plasma and fibrinogen should be reserved for cases of coagulopathy with active bleeding or when an invasive procedure is being considered, particulary in the absence of a concomitant effective antivenom. The local necrosis highlights the potential for significant local sequelae, necessitating cautious but timely surgical intervention.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"274 ","pages":"Article 109021"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating epidemiological evidence and immunodiagnostic development for early diagnosis of Bothrops spp. envenomation in Brazil","authors":"Mariana Fernandes Fonseca ,&nbsp;Alessandra Becker-Finco ,&nbsp;Bianca Prado-Costa ,&nbsp;Guilherme Rabelo Coelho ,&nbsp;Michele Marta Weber-Lima ,&nbsp;João Carlos Degraf Muzzi ,&nbsp;Isabella Gizzi Jiacomini ,&nbsp;Martina Beltramino ,&nbsp;Luciana Aparecida Freitas-de-Sousa ,&nbsp;Patrícia Bianca Clissa ,&nbsp;Juliana Ferreira de Moura ,&nbsp;Larissa Magalhães Alvarenga","doi":"10.1016/j.toxicon.2026.109022","DOIUrl":"10.1016/j.toxicon.2026.109022","url":null,"abstract":"<div><div>Snakebite envenoming remains a major public health issue in Brazil, with <em>Bothrops</em> genus responsible for most cases. To support public health planning, we analyzed epidemiological data from Paraná State and reported, for the first time, a species-level identification of snakes responsible for accidents in this region. The results revealed that <em>Bothrops jararaca</em> accounted for over 85% of cases, followed by <em>Bothrops jararacussu</em>, reinforcing their epidemiological and clinical relevance. Based on this evidence, two monoclonal antibodies were produced by hybridoma technology for application in a diagnostic tool for early identification of <em>Bothrops</em> spp. envenomation. The antibodies were sequenced and immunochemically characterized, and both specifically recognized bothropic metalloproteinases. When applied in a competitive ELISA, the assay detected venom concentrations as low as 60 ng/mL in sera spiked with <em>B. jararaca</em> and <em>Bothrops alternatus</em> and showed no reactivity with other medically relevant genera. Although detection of <em>B. jararacussu</em>, <em>Bothrops moojeni</em> and <em>Bothrops neuwiedi</em> required higher concentrations, these venoms remained detectable, indicating potential for broader application. Further optimization could enhance its sensitivity, enabling more effective detection across a wider spectrum of species. Together, these findings provide novel epidemiological and immunodiagnostic insights, that can guide the development of improved diagnostic platforms for <em>Bothrops</em> spp. envenoming.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"274 ","pages":"Article 109022"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}