Pub Date : 2026-02-06DOI: 10.1016/j.toxicon.2026.109021
Sébastien Larréché , Gael Le Roux , Jean-Philippe Chippaux , Jérémy Hardy , Anne-Laure Fédou , Magali Labadie
Background
Atheris 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 A. chlorechis envenoming presenting with venom-induced consumption coagulopathy (VICC), snakebite-associated thrombotic microangiopathy (TMA), and local necrosis.
Case presentation
A 33-year-old man was bitten on the index finger by a captive A. chlorechis. 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.
Conclusion
This case demonstrates that A. chlorechis 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 Atheris 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.
{"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 , Gael Le Roux , Jean-Philippe Chippaux , Jérémy Hardy , Anne-Laure Fédou , 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":"2026-02-06","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}
Pub Date : 2026-02-06DOI: 10.1016/j.toxicon.2026.109022
Mariana Fernandes Fonseca , Alessandra Becker-Finco , Bianca Prado-Costa , Guilherme Rabelo Coelho , Michele Marta Weber-Lima , João Carlos Degraf Muzzi , Isabella Gizzi Jiacomini , Martina Beltramino , Luciana Aparecida Freitas-de-Sousa , Patrícia Bianca Clissa , Juliana Ferreira de Moura , Larissa Magalhães Alvarenga
Snakebite envenoming remains a major public health issue in Brazil, with Bothrops 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 Bothrops jararaca accounted for over 85% of cases, followed by Bothrops jararacussu, 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 Bothrops 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 B. jararaca and Bothrops alternatus and showed no reactivity with other medically relevant genera. Although detection of B. jararacussu, Bothrops moojeni and Bothrops neuwiedi 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 Bothrops spp. envenoming.
{"title":"Integrating epidemiological evidence and immunodiagnostic development for early diagnosis of Bothrops spp. envenomation in Brazil","authors":"Mariana Fernandes Fonseca , Alessandra Becker-Finco , Bianca Prado-Costa , Guilherme Rabelo Coelho , Michele Marta Weber-Lima , João Carlos Degraf Muzzi , Isabella Gizzi Jiacomini , Martina Beltramino , Luciana Aparecida Freitas-de-Sousa , Patrícia Bianca Clissa , Juliana Ferreira de Moura , 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":"2026-02-06","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}
Pub Date : 2026-02-05DOI: 10.1016/j.toxicon.2026.109023
Abderrezak Khelfi
Snake venoms represent a vast reservoir of bioactive molecules with both toxic and therapeutic potential. The Saharan horned viper (Cerastes cerastes), distributed across North Africa and the Middle East, produces a venom rich in proteins and peptides that modulate key physiological processes. This review synthesizes current knowledge on the pharmacological activities of Cerastes cerastes venom and its purified components, emphasizing their potential applications in medicine. Enzymes such as phospholipases A2, serine proteinases, metalloproteinases, L-amino acid oxidases, and disintegrins have been isolated and characterized, displaying diverse biological effects. These include pro- and anticoagulant activities relevant to hemostasis, cytotoxic and anti-angiogenic properties with implications in cancer therapy, and antiparasitic effects against Leishmania and Schistosoma species. Furthermore, venom-derived L-amino acid oxidases exhibit strong antibacterial activity, particularly against resistant pathogens such as MRSA, while emerging evidence highlights immunomodulatory and radioprotective roles. Despite their promise, challenges related to toxicity, stability, delivery, and potential immunogenicity must be addressed for successful clinical translation. Collectively, Cerastes cerastes venom exemplifies the therapeutic versatility of natural toxins and offers a valuable platform for the discovery and development of novel agents targeting cancer, infectious diseases, hemostatic disorders, and immune-mediated conditions.
{"title":"Therapeutic potentials of Cerastes cerastes venom: A comprehensive review of bioactive molecules and biomedical applications","authors":"Abderrezak Khelfi","doi":"10.1016/j.toxicon.2026.109023","DOIUrl":"10.1016/j.toxicon.2026.109023","url":null,"abstract":"<div><div>Snake venoms represent a vast reservoir of bioactive molecules with both toxic and therapeutic potential. The Saharan horned viper (<em>Cerastes cerastes</em>), distributed across North Africa and the Middle East, produces a venom rich in proteins and peptides that modulate key physiological processes. This review synthesizes current knowledge on the pharmacological activities of <em>Cerastes cerastes</em> venom and its purified components, emphasizing their potential applications in medicine. Enzymes such as phospholipases A<sub>2</sub>, serine proteinases, metalloproteinases, L-amino acid oxidases, and disintegrins have been isolated and characterized, displaying diverse biological effects. These include pro- and anticoagulant activities relevant to hemostasis, cytotoxic and anti-angiogenic properties with implications in cancer therapy, and antiparasitic effects against <em>Leishmania</em> and <em>Schistosoma</em> species. Furthermore, venom-derived L-amino acid oxidases exhibit strong antibacterial activity, particularly against resistant pathogens such as MRSA, while emerging evidence highlights immunomodulatory and radioprotective roles. Despite their promise, challenges related to toxicity, stability, delivery, and potential immunogenicity must be addressed for successful clinical translation. Collectively, <em>Cerastes cerastes</em> venom exemplifies the therapeutic versatility of natural toxins and offers a valuable platform for the discovery and development of novel agents targeting cancer, infectious diseases, hemostatic disorders, and immune-mediated conditions.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"274 ","pages":"Article 109023"},"PeriodicalIF":2.4,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137825","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}
Pub Date : 2026-01-31DOI: 10.1016/j.toxicon.2026.109017
Christina Sahyoun, Damien Redureau, Thomas Crasset, Rudy Fourmy, Aude Violette, Vincent Leignel, Ziad Fajloun, César Mattei, Christian Legros, Loïc Quinton
Proteomic characterization of snake venoms is essential for understanding the molecular basis of their evolution and for identifying bioactive compounds of therapeutic interest. The Montivipera species endemic to the Near and Middle East region remain poorly studied despite their interesting biological activities. Previous analyses of Montivipera venoms have provided only partial proteomic profiles, with notable discrepancies between studies. To address this gap, we conducted a proteomic analysis of five Montivipera species, including M. bornmuelleri, M. bulgardaghica, M. albizona, M. raddei and M. xanthina. We also analyzed the venom of Macrovipera lebetina ssp. to provide a broader comparative framework. These venoms were investigated using an integrated approach combining SDS-PAGE, RP-HPLC and shotgun proteomics, using both trypsin and multi-enzymatic limited digestions to maximize protein identification and coverage. SDS-PAGE and RP-HPLC analyses revealed the remarkable complexity and diversity of Montivipera venoms, which were further confirmed by shotgun proteomics, identifying between 129 and 179 proteins and peptides per species. The major protein families detected included snake venom metalloproteinases, phospholipases A2, venom serine proteases, C-type lectins, venom vascular-endothelial growth factors, and disintegrins. Notably, the relative abundance of these protein families varied across species, suggesting interspecific differences in envenomation profiles. Comparative analysis revealed a high degree of similarity among Montivipera species, with 39 shared proteins across all five venoms. Our findings confirmed the major toxin families previously reported in Montivipera venoms and revealed the presence of several low-abundance protein families that were not previously identified. Thus, this study highlights both the conserved and unique features of Montivipera venom proteomes, offering a valuable foundation for future functional and evolutionary investigations.
蛇毒的蛋白质组学特征对于了解其进化的分子基础和鉴定具有治疗意义的生物活性化合物至关重要。近东和中东地区特有的Montivipera物种尽管具有有趣的生物活动，但研究仍然很少。先前对Montivipera毒液的分析只提供了部分蛋白质组谱，研究之间存在显著差异。为了解决这一空白，我们对5种Montivipera进行了蛋白质组学分析，包括M. bornmuelleri， M. bulgardaghica， M. albizona， M. raddei和M. xanthina。并对其毒液进行了分析。提供一个更广泛的比较框架。采用SDS-PAGE、RP-HPLC和鸟枪蛋白质组学相结合的综合方法对这些毒液进行了研究，利用胰蛋白酶和多酶限制性消化来最大限度地鉴定和覆盖蛋白质。SDS-PAGE和RP-HPLC分析显示，Montivipera毒液具有显著的复杂性和多样性，霰弹枪蛋白质组学进一步证实了这一点，每个物种鉴定出129 ~ 179种蛋白质和肽。检测到的主要蛋白家族包括蛇毒金属蛋白酶、磷脂酶A2、蛇毒丝氨酸蛋白酶、c型凝集素、蛇毒血管内皮生长因子和崩解素。值得注意的是，这些蛋白家族的相对丰度在不同物种之间存在差异，这表明在毒液谱上存在种间差异。比较分析显示，Montivipera物种之间高度相似，在所有五种毒液中有39种共享蛋白质。我们的发现证实了以前在Montivipera毒液中报道的主要毒素家族，并揭示了几个以前未发现的低丰度蛋白质家族的存在。因此，本研究突出了Montivipera毒液蛋白质组的保守性和独特性，为未来的功能和进化研究提供了有价值的基础。
{"title":"Comparative proteomic analysis reveals functional and evolutionary diversity in five Montivipera snake venoms.","authors":"Christina Sahyoun, Damien Redureau, Thomas Crasset, Rudy Fourmy, Aude Violette, Vincent Leignel, Ziad Fajloun, César Mattei, Christian Legros, Loïc Quinton","doi":"10.1016/j.toxicon.2026.109017","DOIUrl":"https://doi.org/10.1016/j.toxicon.2026.109017","url":null,"abstract":"<p><p>Proteomic characterization of snake venoms is essential for understanding the molecular basis of their evolution and for identifying bioactive compounds of therapeutic interest. The Montivipera species endemic to the Near and Middle East region remain poorly studied despite their interesting biological activities. Previous analyses of Montivipera venoms have provided only partial proteomic profiles, with notable discrepancies between studies. To address this gap, we conducted a proteomic analysis of five Montivipera species, including M. bornmuelleri, M. bulgardaghica, M. albizona, M. raddei and M. xanthina. We also analyzed the venom of Macrovipera lebetina ssp. to provide a broader comparative framework. These venoms were investigated using an integrated approach combining SDS-PAGE, RP-HPLC and shotgun proteomics, using both trypsin and multi-enzymatic limited digestions to maximize protein identification and coverage. SDS-PAGE and RP-HPLC analyses revealed the remarkable complexity and diversity of Montivipera venoms, which were further confirmed by shotgun proteomics, identifying between 129 and 179 proteins and peptides per species. The major protein families detected included snake venom metalloproteinases, phospholipases A<sub>2</sub>, venom serine proteases, C-type lectins, venom vascular-endothelial growth factors, and disintegrins. Notably, the relative abundance of these protein families varied across species, suggesting interspecific differences in envenomation profiles. Comparative analysis revealed a high degree of similarity among Montivipera species, with 39 shared proteins across all five venoms. Our findings confirmed the major toxin families previously reported in Montivipera venoms and revealed the presence of several low-abundance protein families that were not previously identified. Thus, this study highlights both the conserved and unique features of Montivipera venom proteomes, offering a valuable foundation for future functional and evolutionary investigations.</p>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":" ","pages":"109017"},"PeriodicalIF":2.4,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146107291","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}
Pub Date : 2026-01-29DOI: 10.1016/j.toxicon.2026.109019
Wei Tang , Jinfeng Zhao , Kai Liu , Peng Liao
This study investigated the protective role of rosemary extract (RE) against intestinal inflammation induced by deoxynivalenol (DON) in weaned piglets. Sixty piglets were randomly allocated to three dietary treatments for a 21-day period: a basal diet (Control), a basal diet supplemented with 1.5 mg/kg DON (DON group), and a basal diet containing 200 mg/kg RE plus 1.5 mg/kg DON (RE + DON group). Dietary RE supplementation alleviated the negative impacts of DON on growth performance and organ indices (liver and spleen), while also improving DON-induced alterations in serum biochemical markers. RE effectively reduced intestinal oxidative stress, as evidenced by decreased concentrations of malondialdehyde (MDA) and reactive oxygen species (ROS), along with restored activities of glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), and superoxide dismutase (SOD) in the intestinal mucosa. Moreover, DON exposure increased the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and decreased anti-inflammatory cytokines (e.g., TGF-β, IL-10) in the mucosa, whereas RE supplementation significantly restored cytokine balance. At the molecular level, DON inhibited the Nrf2-Keap1 antioxidant pathway, while RE enhanced the expression of Nrf2, Keap1, and the downstream targets HO-1 and NQO1, thereby mitigating oxidative damage. Furthermore, RE suppressed the DON-induced activation of MAPK (ERK, p38, JNK) and NF-κB p65 signaling pathways, which contributed to the reduction of mucosal inflammation. In summary, RE attenuates DON-induced intestinal injury in weaned piglets by activating the Nrf2/HO-1 antioxidant pathway and inhibiting the MAPK/NF-κB inflammatory signaling cascade.
本研究探讨了迷迭香提取物（RE）对脱氧雪腐镰刀菌醇（DON）诱导的断奶仔猪肠道炎症的保护作用。将60头仔猪随机分为基础饲粮（对照组）、基础饲粮中添加1.5 mg/kg DON （DON组）和基础饲粮中添加200 mg/kg RE + 1.5 mg/kg DON （RE + DON组），试验期21 d。饲粮中添加RE可缓解DON对生长性能和器官指数（肝脏和脾脏）的负面影响，同时改善DON引起的血清生化指标的改变。RE可有效降低肠道氧化应激，降低丙二醛（MDA）和活性氧（ROS）浓度，恢复肠黏膜谷胱甘肽过氧化物酶（GSH-Px）、总抗氧化能力（T-AOC）和超氧化物歧化酶（SOD）活性。此外，DON暴露增加了粘膜中促炎细胞因子（TNF-α、IL-1β、IL-6）的表达，降低了抗炎细胞因子（TGF-β、IL-10）的表达，而补充RE可显著恢复细胞因子平衡。在分子水平上，DON抑制Nrf2-Keap1抗氧化途径，而RE增强Nrf2、Keap1及其下游靶点HO-1和NQO1的表达，从而减轻氧化损伤。此外，RE抑制don诱导的MAPK （ERK, p38， JNK）和NF-κB p65信号通路的激活，有助于减轻粘膜炎症。综上所述，RE通过激活Nrf2/HO-1抗氧化途径和抑制MAPK/NF-κB炎症信号级联来减轻don诱导的断奶仔猪肠道损伤。
{"title":"Rosemary extract mitigates deoxynivalenol-induced intestinal inflammation in weaned piglets via activation of the Nrf2/HO-1 pathway and suppression of NF-κB/MAPK signaling","authors":"Wei Tang , Jinfeng Zhao , Kai Liu , Peng Liao","doi":"10.1016/j.toxicon.2026.109019","DOIUrl":"10.1016/j.toxicon.2026.109019","url":null,"abstract":"<div><div>This study investigated the protective role of rosemary extract (RE) against intestinal inflammation induced by deoxynivalenol (DON) in weaned piglets. Sixty piglets were randomly allocated to three dietary treatments for a 21-day period: a basal diet (Control), a basal diet supplemented with 1.5 mg/kg DON (DON group), and a basal diet containing 200 mg/kg RE plus 1.5 mg/kg DON (RE + DON group). Dietary RE supplementation alleviated the negative impacts of DON on growth performance and organ indices (liver and spleen), while also improving DON-induced alterations in serum biochemical markers. RE effectively reduced intestinal oxidative stress, as evidenced by decreased concentrations of malondialdehyde (MDA) and reactive oxygen species (ROS), along with restored activities of glutathione peroxidase (GSH-P<em>x</em>), total antioxidant capacity (T-AOC), and superoxide dismutase (SOD) in the intestinal mucosa. Moreover, DON exposure increased the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and decreased anti-inflammatory cytokines (e.g., TGF-β, IL-10) in the mucosa, whereas RE supplementation significantly restored cytokine balance. At the molecular level, DON inhibited the Nrf2-Keap1 antioxidant pathway, while RE enhanced the expression of Nrf2, Keap1, and the downstream targets HO-1 and NQO1, thereby mitigating oxidative damage. Furthermore, RE suppressed the DON-induced activation of MAPK (ERK, p38, JNK) and NF-<em>κ</em>B p65 signaling pathways, which contributed to the reduction of mucosal inflammation. In summary, RE attenuates DON-induced intestinal injury in weaned piglets by activating the Nrf2/HO-1 antioxidant pathway and inhibiting the MAPK/NF-<em>κ</em>B inflammatory signaling cascade.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"273 ","pages":"Article 109019"},"PeriodicalIF":2.4,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146080334","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}
Pub Date : 2026-01-27DOI: 10.1016/j.toxicon.2026.109015
Dalong Wang , Xiaopeng Chen , Yueyue Li , Yingying Wang , Yaojun Wang , Zujia Chen , Jingjing Wu , Chong Wang
Epimedium, a traditional herbal medicine with a wide range of pharmacological uses, has been linked to adverse effects, including nephrotoxicity. Nevertheless, the specific toxic components and underlying mechanisms remain elusive. This research examined the nephrotoxic effects of icarisid I, a major flavonoid metabolite of Epimedium, and delved into its molecular mechanisms. The study demonstrated that icarisid I induces significant nephrotoxicity both in vitro and in vivo. In HK-2 cells, it triggered oxidative stress, indicated by altered SOD, GSH, and MDA levels, and induced apoptosis. In mice, it caused severe renal tubular damage and elevated plasma BUN and creatinine. Mechanistically, icarisid I potentially inhibited the PI3K/AKT pathway, leading to the suppression of Nrf2 and its downstream target HO-1. We conclude that icarisid I contributes to the nephrotoxicity by inducing oxidative stress and apoptosis via suppression of the PI3K/AKT/Nrf2/HO-1 pathway, a finding critical for the safety evaluation of Epimedium-derived compounds.
{"title":"Epimedium-derived icarisid I induces oxidative stress and nephrotoxicity by suppressing PI3K/AKT/Nrf2/HO-1 signaling pathway","authors":"Dalong Wang , Xiaopeng Chen , Yueyue Li , Yingying Wang , Yaojun Wang , Zujia Chen , Jingjing Wu , Chong Wang","doi":"10.1016/j.toxicon.2026.109015","DOIUrl":"10.1016/j.toxicon.2026.109015","url":null,"abstract":"<div><div>Epimedium, a traditional herbal medicine with a wide range of pharmacological uses, has been linked to adverse effects, including nephrotoxicity. Nevertheless, the specific toxic components and underlying mechanisms remain elusive. This research examined the nephrotoxic effects of icarisid I, a major flavonoid metabolite of <em>Epimedium</em>, and delved into its molecular mechanisms. The study demonstrated that icarisid I induces significant nephrotoxicity both <em>in vitro</em> and <em>in vivo</em>. In HK-2 cells, it triggered oxidative stress, indicated by altered SOD, GSH, and MDA levels, and induced apoptosis. In mice, it caused severe renal tubular damage and elevated plasma BUN and creatinine. Mechanistically, icarisid I potentially inhibited the PI3K/AKT pathway, leading to the suppression of Nrf2 and its downstream target HO-1. We conclude that icarisid I contributes to the nephrotoxicity by inducing oxidative stress and apoptosis via suppression of the PI3K/AKT/Nrf2/HO-1 pathway, a finding critical for the safety evaluation of <em>Epimedium</em>-derived compounds.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"273 ","pages":"Article 109015"},"PeriodicalIF":2.4,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146080335","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}
Pub Date : 2026-01-24DOI: 10.1016/j.toxicon.2026.109012
G.V. Malykin, M.S. Puzanov, P.V. Velansky, V.G. Kuznetsov, T. Yu Magarlamov
We, for the first time, have carried out a search for tetrodotoxin and its analogues (TTXs) in extracts of various animals being potential diet items for highly toxic nemerteans Cephalothrix cf. simula using high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). We have screened TTXs in a total of 57 specimens from 2 classes. Рresence of TTX from five polychaetes species belonging to three families was shown. We here discuss the role of diet items as a source of TTXs for carnivorous TTX-bearing animals.
{"title":"Tetrodotoxin in diet items of highly toxic ribbon worm Cephalothrix cf. simula (Palaeonemertea, Nemertea)","authors":"G.V. Malykin, M.S. Puzanov, P.V. Velansky, V.G. Kuznetsov, T. Yu Magarlamov","doi":"10.1016/j.toxicon.2026.109012","DOIUrl":"10.1016/j.toxicon.2026.109012","url":null,"abstract":"<div><div>We, for the first time, have carried out a search for tetrodotoxin and its analogues (TTXs) in extracts of various animals being potential diet items for highly toxic nemerteans <em>Cephalothrix</em> cf. <em>simula</em> using high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). We have screened TTXs in a total of 57 specimens from 2 classes. Рresence of TTX from five polychaetes species belonging to three families was shown. We here discuss the role of diet items as a source of TTXs for carnivorous TTX-bearing animals.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"273 ","pages":"Article 109012"},"PeriodicalIF":2.4,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053996","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}
Pub Date : 2026-01-24DOI: 10.1016/j.toxicon.2026.109014
Yusuf Ali , Shamsiddin Fazliddinov , Ailin Hu , Naziermu Dongmulati , Han He , Zi Yang , Yanhua Gao , Ahmidin Wali , Haji Akber Aisa , Sharafitdin Mirzaakhmedov , Akmal Asrorov , Abulimiti Yili
Scorpion venom is a heterogeneous mixture of proteins and peptides, many of which have multiple bioactivities, including antitumor activity, modulation of ion channels, analgesia, and anti-inflammatory effects. This study, two peptides named BmKNT1 and BmKNT2 were isolated and purified from the Buthus martensii Karsch (BmK) venom by gel filtration chromatography (GFC), ion-exchange chromatography (IEC) and Reverse phase high-performance liquid chromatography (RP-HPLC), respectively. The primary structure of BmKNT1 (69 amino acid residues, theoretical pI/Mw: 7.66/7660.5 Da) and BmKNT2 (64 amino acid residues, theoretical pI/Mw: May 6, 7270.33) were determined by a combination of Edman degradation and MALDI-TOF-MS/MS sequencing analysis. It showed a high similarity to that of other scorpion neurotoxins. The Effects of both neurotoxins on Na+-channel, K+-channel and Ca2+-channel in rat dorsal root ganglion (DRG) were determined at 100 μg/ml. The results showed BmKNT2 had inhibitory activity on K+-channels expressed on DRG cells, which is a typical characteristic of voltage-gated potassium channel pore area inhibitors. On the contrary, BmKNT1 has activation activity on the K+-channel in rat DRG, and both toxins have inhibitory activity on Ca2+-channels in rat DRG.
{"title":"Purification and Characterization of Two Neurotoxins BmKNT1 and BmKNT2 from the Scorpion Buthus martensii karsch venom","authors":"Yusuf Ali , Shamsiddin Fazliddinov , Ailin Hu , Naziermu Dongmulati , Han He , Zi Yang , Yanhua Gao , Ahmidin Wali , Haji Akber Aisa , Sharafitdin Mirzaakhmedov , Akmal Asrorov , Abulimiti Yili","doi":"10.1016/j.toxicon.2026.109014","DOIUrl":"10.1016/j.toxicon.2026.109014","url":null,"abstract":"<div><div>Scorpion venom is a heterogeneous mixture of proteins and peptides, many of which have multiple bioactivities, including antitumor activity, modulation of ion channels, analgesia, and anti-inflammatory effects. This study, two peptides named BmKNT1 and BmKNT2 were isolated and purified from the <em>Buthus martensii</em> Karsch (BmK) venom by gel filtration chromatography (GFC), ion-exchange chromatography (IEC) and Reverse phase high-performance liquid chromatography (RP-HPLC), respectively. The primary structure of BmKNT1 (69 amino acid residues, theoretical pI/Mw: 7.66/7660.5 Da) and BmKNT2 (64 amino acid residues, theoretical pI/Mw: May 6, 7270.33) were determined by a combination of Edman degradation and MALDI-TOF-MS/MS sequencing analysis. It showed a high similarity to that of other scorpion neurotoxins. The Effects of both neurotoxins on Na<sup>+</sup>-channel, K<sup>+</sup>-channel and Ca<sup>2+</sup>-channel in rat dorsal root ganglion (DRG) were determined at 100 μg/ml. The results showed BmKNT2 had inhibitory activity on K<sup>+</sup>-channels expressed on DRG cells, which is a typical characteristic of voltage-gated potassium channel pore area inhibitors. On the contrary, BmKNT1 has activation activity on the K<sup>+</sup>-channel in rat DRG, and both toxins have inhibitory activity on Ca<sup>2+</sup>-channels in rat DRG.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"273 ","pages":"Article 109014"},"PeriodicalIF":2.4,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053903","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}
Pub Date : 2026-01-24DOI: 10.1016/j.toxicon.2026.109011
Joshua R. Evans , Daniel G. Beach , Jake Stillwell , Meghann Bruce , Adrian Reyes-Prieto , Cecilio Valadez-Cano , Pearse McCarron , Janice Lawrence
The abundance of the anaC gene, which is involved in anatoxin biosynthesis, correlated with anatoxin concentration (rs = 0.80, p < 0.0001) in Atlantic Canadian benthic freshwater samples. Average total anatoxins (100 μg g−1 by high resolution mass spectrometry) and anaC (4.7 x 108 copies g−1 by droplet digital PCR) were highest in August, while highest average toxin quota (8.9 pg anaC−1) was observed in July. Pairing approaches provided insight into the seasonality of anatoxin biosynthesis.
{"title":"Anatoxin biosynthesis gene abundance correlates with anatoxin concentration in freshwater benthic samples","authors":"Joshua R. Evans , Daniel G. Beach , Jake Stillwell , Meghann Bruce , Adrian Reyes-Prieto , Cecilio Valadez-Cano , Pearse McCarron , Janice Lawrence","doi":"10.1016/j.toxicon.2026.109011","DOIUrl":"10.1016/j.toxicon.2026.109011","url":null,"abstract":"<div><div>The abundance of the <em>anaC</em> gene, which is involved in anatoxin biosynthesis, correlated with anatoxin concentration (rs = 0.80, p < 0.0001) in Atlantic Canadian benthic freshwater samples. Average total anatoxins (100 μg g<sup>−1</sup> by high resolution mass spectrometry) and <em>anaC</em> (4.7 x 10<sup>8</sup> copies g<sup>−1</sup> by droplet digital PCR) were highest in August, while highest average toxin quota (8.9 pg <em>anaC</em><sup>−1</sup>) was observed in July. Pairing approaches provided insight into the seasonality of anatoxin biosynthesis.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"273 ","pages":"Article 109011"},"PeriodicalIF":2.4,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053913","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}
Pub Date : 2026-01-24DOI: 10.1016/j.toxicon.2026.109002
Cainã Aillén Ouriques Oliveira , Thailan Arlindo da Silva , Rafael David Souto de Azevedo , Josefa Gerlane da Silva , Jaianne Keitt Alves de Melo , Pedro Gregório Vieira Aquino , Taciana Rabelo Ramalho Ramos
Cenostigma pyramidale is a plant native to the Caatinga biome of northeastern Brazil, which has been reported to cause congenital malformations, spontaneous abortion, and perinatal mortality in fetuses of goats and sheep. Although several bioactive compounds have been identified in this plant, none have been directly associated with the toxic effects in animals. Therefore, the aim of this study was to evaluate the embryotoxic and teratogenic potential of C. pyramidale extract in zebrafish (Danio rerio) and investigate their association with the plant's bioactive compounds. The aerial parts were extracted with ethanol, and the resulting extracts were successively partitioned with hexane, chloroform, and ethyl acetate. The brine shrimp (Artemia salina) lethality assay was used as a screening method by calculating the median lethal concentration (LC50). The chloroform fraction (CF) of C. pyramidale fruits showed the lowest LC50 (184 ppm) and, therefore, it was used in the identification of compounds by gas chromatography coupled with mass spectrometry and in the Fish Embryo Acute Toxicity test. Superoxide dismutase (SOD) and catalase (CAT) activities were evaluated in the embryos. Dose-dependent lethality, delayed development in viable embryos, bradycardia, and teratogenic defects, such as tail malformations pericardial edema, and scoliosis were observed. CAT activity increased with increasing extract concentration. Among the compounds identified, steroids (sitosterol, campesterol, and cholesterol) and palmitic acid were identified as potential toxic agents. The results show that the CF from C. pyramidale fruits exhibits embryotoxic and teratogenic potential in zebrafish, possibly associated with the isolated or synergistic action of these compounds.
{"title":"Evaluation of embryotoxicity and teratogenicity of Cenostigma pyramidale (Tul.) fruit extract in zebrafish (Danio rerio)","authors":"Cainã Aillén Ouriques Oliveira , Thailan Arlindo da Silva , Rafael David Souto de Azevedo , Josefa Gerlane da Silva , Jaianne Keitt Alves de Melo , Pedro Gregório Vieira Aquino , Taciana Rabelo Ramalho Ramos","doi":"10.1016/j.toxicon.2026.109002","DOIUrl":"10.1016/j.toxicon.2026.109002","url":null,"abstract":"<div><div><em>Cenostigma pyramidale</em> is a plant native to the Caatinga biome of northeastern Brazil, which has been reported to cause congenital malformations, spontaneous abortion, and perinatal mortality in fetuses of goats and sheep. Although several bioactive compounds have been identified in this plant, none have been directly associated with the toxic effects in animals. Therefore, the aim of this study was to evaluate the embryotoxic and teratogenic potential of <em>C. pyramidale</em> extract in zebrafish (<em>Danio rerio</em>) and investigate their association with the plant's bioactive compounds. The aerial parts were extracted with ethanol, and the resulting extracts were successively partitioned with hexane, chloroform, and ethyl acetate. The brine shrimp (<em>Artemia salina</em>) lethality assay was used as a screening method by calculating the median lethal concentration (LC<sub>50</sub>). The chloroform fraction (CF) of <em>C. pyramidale</em> fruits showed the lowest LC<sub>50</sub> (184 ppm) and, therefore, it was used in the identification of compounds by gas chromatography coupled with mass spectrometry and in the Fish Embryo Acute Toxicity test. Superoxide dismutase (SOD) and catalase (CAT) activities were evaluated in the embryos. Dose-dependent lethality, delayed development in viable embryos, bradycardia, and teratogenic defects, such as tail malformations pericardial edema, and scoliosis were observed. CAT activity increased with increasing extract concentration. Among the compounds identified, steroids (sitosterol, campesterol, and cholesterol) and palmitic acid were identified as potential toxic agents. The results show that the CF from <em>C. pyramidale</em> fruits exhibits embryotoxic and teratogenic potential in zebrafish, possibly associated with the isolated or synergistic action of these compounds.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"273 ","pages":"Article 109002"},"PeriodicalIF":2.4,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053893","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}
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