Pub Date : 2026-01-13DOI: 10.1016/j.toxicon.2026.108998
Congcheng Zhang, Qin Zhang, Pan Wang, Hai Yin, Yiling Liu, Shuhang Zhang, Hao Lu
Pyrrolizidine alkaloids (PAs) occur in approximately 3 %–5 % of flowering plants and are common natural toxins; retrorsine is among the most hepatotoxic. Ingestion of PA-containing products is a major cause of hepatic sinusoidal obstruction syndrome (HSOS). To elucidate the mechanism of retrorsine-induced hepatotoxicity, we combined network toxicology, molecular docking, and functional assays in primary hepatocytes. We identified 136 HSOS-related targets enriched in calcium signaling and PI3K-AKT pathways, including AKT1, JUN, and EGFR. In primary rat hepatocytes, retrorsine significantly decreased p-AKT, p-EGFR, and p-c-Jun levels (p < 0.05). Together, these data suggest that retrorsine inhibits EGFR/AKT/c-Jun axis and triggers intracellular calcium overload, leading to ER stress-associated autophagy and hepatocyte death. These findings reveal a mechanism of retrorsine-induced hepatocyte injury and highlight the EGFR/AKT/c-Jun survival pathway as a potential therapeutic target in PA-induced HSOS.
{"title":"Retrorsine-induced hepatotoxicity is mediated by inhibition of the EGFR/AKT/c-Jun axis and disruption of calcium homeostasis in primary hepatocytes","authors":"Congcheng Zhang, Qin Zhang, Pan Wang, Hai Yin, Yiling Liu, Shuhang Zhang, Hao Lu","doi":"10.1016/j.toxicon.2026.108998","DOIUrl":"10.1016/j.toxicon.2026.108998","url":null,"abstract":"<div><div>Pyrrolizidine alkaloids (PAs) occur in approximately 3 %–5 % of flowering plants and are common natural toxins; retrorsine is among the most hepatotoxic. Ingestion of PA-containing products is a major cause of hepatic sinusoidal obstruction syndrome (HSOS). To elucidate the mechanism of retrorsine-induced hepatotoxicity, we combined network toxicology, molecular docking, and functional assays in primary hepatocytes. We identified 136 HSOS-related targets enriched in calcium signaling and PI3K-AKT pathways, including AKT1, JUN, and EGFR. In primary rat hepatocytes, retrorsine significantly decreased p-AKT, p-EGFR, and p-c-Jun levels (<em>p</em> < 0.05). Together, these data suggest that retrorsine inhibits EGFR/AKT/c-Jun axis and triggers intracellular calcium overload, leading to ER stress-associated autophagy and hepatocyte death. These findings reveal a mechanism of retrorsine-induced hepatocyte injury and highlight the EGFR/AKT/c-Jun survival pathway as a potential therapeutic target in PA-induced HSOS.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"272 ","pages":"Article 108998"},"PeriodicalIF":2.4,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145979115","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}
The health of humans and livestock is significantly compromised by the pervasive and serious issue of mycotoxin contamination in crops. Exploring ways to eliminate mycotoxin contamination is a global concern. In vivo biological prevention and treatment of mycotoxin damage demand a comprehensive understanding of its harm mechanisms, which is essential for developing comprehensive strategies. This study aimed to systematically review the mechanisms by which mycotoxin contamination damages the organism, causing oxidative stress, cellular apoptosis, autophagy, ferroptosis, and via the gut–liver axis, gut–testis axis, and gut–immune axis, causing damage to multiple organs. Further, we explored a range of biological control measures, showing that supplementing diets and animal feed with plant extracts, trace elements, probiotics, and other additives effectively mitigates the damage caused by mycotoxin exposure. This review examines the feasibility and limitations of combined strategies utilizing trace element selenium, probiotics, and plant extracts, aiming to provide a promising approach for the prevention and control of mycotoxin contamination.
{"title":"Detriment of mycotoxin contamination in feed and nutrition-based prevention and control strategies: A review","authors":"Shijie Fan, Kunru Teng, Jiefeng Li, Beibei He, Aike Li, Weiwei Wang, Jing Zhang","doi":"10.1016/j.toxicon.2026.108996","DOIUrl":"10.1016/j.toxicon.2026.108996","url":null,"abstract":"<div><div>The health of humans and livestock is significantly compromised by the pervasive and serious issue of mycotoxin contamination in crops. Exploring ways to eliminate mycotoxin contamination is a global concern. In vivo biological prevention and treatment of mycotoxin damage demand a comprehensive understanding of its harm mechanisms, which is essential for developing comprehensive strategies. This study aimed to systematically review the mechanisms by which mycotoxin contamination damages the organism, causing oxidative stress, cellular apoptosis, autophagy, ferroptosis, and via the gut–liver axis, gut–testis axis, and gut–immune axis, causing damage to multiple organs. Further, we explored a range of biological control measures, showing that supplementing diets and animal feed with plant extracts, trace elements, probiotics, and other additives effectively mitigates the damage caused by mycotoxin exposure. This review examines the feasibility and limitations of combined strategies utilizing trace element selenium, probiotics, and plant extracts, aiming to provide a promising approach for the prevention and control of mycotoxin contamination.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"273 ","pages":"Article 108996"},"PeriodicalIF":2.4,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145990867","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}
Fish venoms constitute highly specialized biochemical systems, yet their molecular composition and gene-expression architecture remain poorly resolved in many venomous teleosts. In lionfishes, venom is delivered through fin-associated spines, but transcriptome-level insights into spine-specific venom production are largely absent, particularly for the dwarf lionfish Neochirus brachypterus. The lack of species-specific molecular resources has hindered systematic identification of venom-associated genes, functional pathways, and evolutionary relationships of toxins within this lineage. Addressing this knowledge gap, the present study provides the first comprehensive transcriptomic analysis of venomous spine tissue in N. brachypterus (Dwarf lionfish), a poorly characterized lionfish species. Functional annotation against the NR and UniProt Swiss-Prot databases revealed a substantial portion of unannotated transcripts reflecting current limitations in assembly completeness. However, InterProScan analysis identified 1459 unique Pfam domains and 599 superfamilies, indicating a functionally diverse transcriptome enriched in structural, signaling, and transport-related domains. Gene Ontology (GO) enrichment analysis further highlighted the metabolic and regulatory complexity of the venom-producing tissue. Notably, similarity searches against venom and toxin databases identified seven putative toxin homologs, including neoverrucotoxin, stonustoxin, verrucotoxin, and 5′-nucleotidase. These sequences exhibited significant homology to venom components reported from other Scorpaeniformes and distantly related venomous taxa, including snakes, reflecting convergent molecular features rather than shared ecological or functional equivalence. The presence of these toxin-like transcripts suggests potential roles in tissue damage, nociception, and physiological disruption during envenomation, consistent with a defensive venom system. Collectively, this transcriptomic resource advances understanding of the molecular repertoire underlying Neochirus brachypterus venom and establishes a foundation for future studies on the evolution, diversification, and pharmacological potential of lionfish toxins.
{"title":"Transcriptome based functional atlas of venomous spines: A first report on Dwarf lionfish","authors":"Parthkumar Prajapati , Ketankumar Panchal , Prakash Koringa , Subhash Jakhesara , Neelam Nathani , Chandrashekar Mootapally","doi":"10.1016/j.toxicon.2026.108995","DOIUrl":"10.1016/j.toxicon.2026.108995","url":null,"abstract":"<div><div>Fish venoms constitute highly specialized biochemical systems, yet their molecular composition and gene-expression architecture remain poorly resolved in many venomous teleosts. In lionfishes, venom is delivered through fin-associated spines, but transcriptome-level insights into spine-specific venom production are largely absent, particularly for the dwarf lionfish <em>Neochirus brachypterus</em>. The lack of species-specific molecular resources has hindered systematic identification of venom-associated genes, functional pathways, and evolutionary relationships of toxins within this lineage. Addressing this knowledge gap, the present study provides the first comprehensive transcriptomic analysis of venomous spine tissue in <em>N. brachypterus</em> (Dwarf lionfish), a poorly characterized lionfish species. Functional annotation against the NR and UniProt Swiss-Prot databases revealed a substantial portion of unannotated transcripts reflecting current limitations in assembly completeness. However, InterProScan analysis identified 1459 unique Pfam domains and 599 superfamilies, indicating a functionally diverse transcriptome enriched in structural, signaling, and transport-related domains. Gene Ontology (GO) enrichment analysis further highlighted the metabolic and regulatory complexity of the venom-producing tissue. Notably, similarity searches against venom and toxin databases identified seven putative toxin homologs, including neoverrucotoxin, stonustoxin, verrucotoxin, and 5′-nucleotidase. These sequences exhibited significant homology to venom components reported from other Scorpaeniformes and distantly related venomous taxa, including snakes, reflecting convergent molecular features rather than shared ecological or functional equivalence. The presence of these toxin-like transcripts suggests potential roles in tissue damage, nociception, and physiological disruption during envenomation, consistent with a defensive venom system. Collectively, this transcriptomic resource advances understanding of the molecular repertoire underlying <em>Neochirus brachypterus</em> venom and establishes a foundation for future studies on the evolution, diversification, and pharmacological potential of lionfish toxins.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"272 ","pages":"Article 108995"},"PeriodicalIF":2.4,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959963","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 : 2026-01-09DOI: 10.1016/j.toxicon.2026.108994
Martina Beltramino , Isabella Gizzi Jiacomini , Bianca Prado-Costa , Mariana Fernandes Fonseca , João Carlos Degraf Muzzi , Juliana Ferreira de Moura , João Carlos Minozzo , Alessandra Becker-Finco , Larissa M. Alvarenga
Envenomation by Loxosceles spiders is an important public health issue, frequently associated with hemolysis. Although the ABO blood group system influences various diseases, its role in loxoscelism is poorly understood. This study evaluated the effect of ABO types on hemolysis induced by L. intermedia, L. gaucho, and L. laeta venoms, with and without complement. Blood type B erythrocytes showed reduced susceptibility to direct hemolysis, suggesting a potential protective effect and offering new insights for improving loxoscelism management.
{"title":"Influence of the ABO system on the hemolytic activity of medically relevant Loxosceles venoms in Brazil","authors":"Martina Beltramino , Isabella Gizzi Jiacomini , Bianca Prado-Costa , Mariana Fernandes Fonseca , João Carlos Degraf Muzzi , Juliana Ferreira de Moura , João Carlos Minozzo , Alessandra Becker-Finco , Larissa M. Alvarenga","doi":"10.1016/j.toxicon.2026.108994","DOIUrl":"10.1016/j.toxicon.2026.108994","url":null,"abstract":"<div><div>Envenomation by <em>Loxosceles</em> spiders is an important public health issue, frequently associated with hemolysis. Although the ABO blood group system influences various diseases, its role in loxoscelism is poorly understood. This study evaluated the effect of ABO types on hemolysis induced by <em>L. intermedia</em>, <em>L. gaucho</em>, and <em>L. laeta</em> venoms, with and without complement. Blood type B erythrocytes showed reduced susceptibility to direct hemolysis, suggesting a potential protective effect and offering new insights for improving loxoscelism management.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"272 ","pages":"Article 108994"},"PeriodicalIF":2.4,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145953156","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 : 2026-01-08DOI: 10.1016/j.toxicon.2025.108688
Andre F. Batista, Dmitri Leonoudakis, Jonathan Giudice, Conor J. Gallagher
{"title":"Mechanisms of RTP004 Peptide Facilitation of BoNT-A Internalization and SNAP25 Cleavage","authors":"Andre F. Batista, Dmitri Leonoudakis, Jonathan Giudice, Conor J. Gallagher","doi":"10.1016/j.toxicon.2025.108688","DOIUrl":"10.1016/j.toxicon.2025.108688","url":null,"abstract":"","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"271 ","pages":"Article 108688"},"PeriodicalIF":2.4,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145908646","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 : 2026-01-08DOI: 10.1016/j.toxicon.2025.108672
Glynis Ablon , Joel Schlessinger , Sachin Shridharani , Z Paul Lorenc , Sherrif F. Ibrahim , Vince Bertucci , Leslie Baumann , Mark S. Nestor , Inna Prygova
{"title":"RelaBoNT-A Treatment of Glabellar Lines and Lateral Canthal Lines of Different Baseline Severity: Subgroup Analyses of Pooled Phase III Study Data","authors":"Glynis Ablon , Joel Schlessinger , Sachin Shridharani , Z Paul Lorenc , Sherrif F. Ibrahim , Vince Bertucci , Leslie Baumann , Mark S. Nestor , Inna Prygova","doi":"10.1016/j.toxicon.2025.108672","DOIUrl":"10.1016/j.toxicon.2025.108672","url":null,"abstract":"","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"271 ","pages":"Article 108672"},"PeriodicalIF":2.4,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145908650","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":"High-Dose Botulinum Neurotoxin Type A as a Predictive Tool for Selective Dorsal Rhizotomy Outcomes in Pediatric Spastic Diplegia","authors":"Flaminia Frascarelli , Giacomo Esposito , Alessandro De Benedictis , Riccardo Carbonetti , Donatella Lettori","doi":"10.1016/j.toxicon.2025.108746","DOIUrl":"10.1016/j.toxicon.2025.108746","url":null,"abstract":"","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"271 ","pages":"Article 108746"},"PeriodicalIF":2.4,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145908760","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 : 2026-01-08DOI: 10.1016/j.toxicon.2025.108759
Vadim Gusev , Olga Lvova , Tatyana Balueva
{"title":"Use Of Botulinum Toxin in Patients With Dysphagia and Posterior Sialorrhea in Acute Ischemic Stroke","authors":"Vadim Gusev , Olga Lvova , Tatyana Balueva","doi":"10.1016/j.toxicon.2025.108759","DOIUrl":"10.1016/j.toxicon.2025.108759","url":null,"abstract":"","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"271 ","pages":"Article 108759"},"PeriodicalIF":2.4,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145908781","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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