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}
Pub Date : 2026-01-23DOI: 10.1016/j.toxicon.2026.109013
Zhuofeng Jiang, Tingyuan Xing, Yau-Tuen Chan, Cheng Zhang, Yibin Feng, Ning Wang
Aflatoxins are toxic compounds produced by certain molds, primarily Aspergillus flavus and Aspergillus parasiticus. These mycotoxins can contaminate various agricultural products, including grains, nuts, and seeds, posing serious health risks. Similarly, a significant portion of Traditional Chinese Medicines (TCMs) is either cultivated through artificial means or harvested from natural environments, making it susceptible to contamination as well. By addressing these critical aspects, the review aims to enhance the safety and quality of TCMs. Despite extensive research on aflatoxins in food crops, systematic reviews focusing on their contamination in TCMs remain limited. This review aims to bridge this gap by synthesizing current knowledge on storage conditions and detoxification strategies for TCMs vulnerable to aflatoxin contamination.
{"title":"Aflatoxin contamination and detoxification in traditional Chinese medicines","authors":"Zhuofeng Jiang, Tingyuan Xing, Yau-Tuen Chan, Cheng Zhang, Yibin Feng, Ning Wang","doi":"10.1016/j.toxicon.2026.109013","DOIUrl":"10.1016/j.toxicon.2026.109013","url":null,"abstract":"<div><div>Aflatoxins are toxic compounds produced by certain molds, primarily <em>Aspergillus flavus</em> and <em>Aspergillus parasiticus</em>. These mycotoxins can contaminate various agricultural products, including grains, nuts, and seeds, posing serious health risks. Similarly, a significant portion of Traditional Chinese Medicines (TCMs) is either cultivated through artificial means or harvested from natural environments, making it susceptible to contamination as well. By addressing these critical aspects, the review aims to enhance the safety and quality of TCMs. Despite extensive research on aflatoxins in food crops, systematic reviews focusing on their contamination in TCMs remain limited. This review aims to bridge this gap by synthesizing current knowledge on storage conditions and detoxification strategies for TCMs vulnerable to aflatoxin contamination.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"273 ","pages":"Article 109013"},"PeriodicalIF":2.4,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047155","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 : 2026-01-21DOI: 10.1016/j.toxicon.2026.109001
Babafemi Siji Ajisebiola , Okikiola Olaoye Afolabi , Adesola Abigeal Toromade , Samuel Itang Itang , Omotayo Opemipo Oyedara , Akindele Oluwatosin Adeyi , Johannes Andreas Eble
Snake venoms toxins could exert toxicological effect with consequence on reproductive functions following snakebite envenoming. The clinical implications of snakebite envenoming on female reproductive health remains unraveled. This study used an animal model to evaluate the pathophysiological effects of Naja nigricollis venom on female reproductive organs. Thirty female albino rats were randomly selected into three groups (n = 10). Group 1 was the control injected with saline, while groups 2 and 3 were injected intraperitoneally with 0.5 mg/kg (LD25) and 1.0 mg/kg (LD50) of N. nigricollis venom, respectively. The venom lethal doses caused significant decrease in the body weight, organs and relative organs weight of the uterus, uterine tube and the ovary compared to the control. There was dysregulation in hormones secretion as serum levels of follicle stimulating hormone, luteinizing hormone, and estradiol were significantly (p < 0.05) higher in envenomed groups. The venom induced substantial oxidative stress evidenced by elevation of malondialdehyde levels and superoxide dismutase activity, with a concomitant decrease of glutathione levels in the uterus, uterine tube and ovary of the envenomed rats. Inflammatory biomarkers of tumor necrosis factor-alpha and interleukin-1 beta increased significantly (p < 0.05) in the female reproductive organs of the envenomed rats. The venom modulated signaling pathways of protein transcription factors by suppressing Nrf2 activation while, inducing overexpression of NF-κB in the uterus, uterine tube and ovary of envenomed rats. Also, these tissues of the uterus, uterine tube and ovary showed severe pathohistological defects after envenomation. Our findings demonstrated that N. nigricollis envenoming inflicts clinical toxicity on overall female reproductive system.
{"title":"Naja nigricollis venom elicits repro-toxicity in organs of female rats: Clinical implications of snakebite envenoming on reproductive health","authors":"Babafemi Siji Ajisebiola , Okikiola Olaoye Afolabi , Adesola Abigeal Toromade , Samuel Itang Itang , Omotayo Opemipo Oyedara , Akindele Oluwatosin Adeyi , Johannes Andreas Eble","doi":"10.1016/j.toxicon.2026.109001","DOIUrl":"10.1016/j.toxicon.2026.109001","url":null,"abstract":"<div><div>Snake venoms toxins could exert toxicological effect with consequence on reproductive functions following snakebite envenoming. The clinical implications of snakebite envenoming on female reproductive health remains unraveled. This study used an animal model to evaluate the pathophysiological effects of <em>Naja nigricollis</em> venom on female reproductive organs. Thirty female albino rats were randomly selected into three groups (n = 10). Group 1 was the control injected with saline, while groups 2 and 3 were injected intraperitoneally with 0.5 mg/kg (LD<sub>25</sub>) and 1.0 mg/kg (LD<sub>50</sub>) of <em>N. nigricollis</em> venom, respectively. The venom lethal doses caused significant decrease in the body weight, organs and relative organs weight of the uterus, uterine tube and the ovary compared to the control. There was dysregulation in hormones secretion as serum levels of follicle stimulating hormone, luteinizing hormone, and estradiol were significantly (p < 0.05) higher in envenomed groups. The venom induced substantial oxidative stress evidenced by elevation of malondialdehyde levels and superoxide dismutase activity, with a concomitant decrease of glutathione levels in the uterus, uterine tube and ovary of the envenomed rats. Inflammatory biomarkers of tumor necrosis factor-alpha and interleukin-1 beta increased significantly (p < 0.05) in the female reproductive organs of the envenomed rats. The venom modulated signaling pathways of protein transcription factors by suppressing Nrf2 activation while, inducing overexpression of NF-κB in the uterus, uterine tube and ovary of envenomed rats. Also, these tissues of the uterus, uterine tube and ovary showed severe pathohistological defects after envenomation. Our findings demonstrated that <em>N. nigricollis</em> envenoming inflicts clinical toxicity on overall female reproductive system.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"273 ","pages":"Article 109001"},"PeriodicalIF":2.4,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146041771","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 : 2026-01-19DOI: 10.1016/j.toxicon.2026.108999
Franklin Riet-Correa , Juan F. Micheloud , Mizael Machado , Fabio S. Mendonça , Ana Lucia Schild , Francisco A. Uzal , Ricardo A.A. Lemos
The objective of this paper is to review the information on toxic plants for ruminants and horses in South America, a continent in which there are 237 plants known to be toxic for livestock. Predisposing factors for plant toxicity include parts or vegetative state of the plants consumed, sprouting after rains, toxic dose, social facilitation, palatability, hunger, thirst, naivete, ingestion period, susceptibility/resistance, transportation, climatic alterations, and environmental degradation. Toxic plants can be forage or non-forage species. The latter can be invasive plants from other regions or from the same region. For the diagnosis of plant poisoning caused by known active compounds, the detection of these substances in the plants and/or animals, coupled with clinical signs, clinical and anatomic pathology, is necessary to confirm the diagnosis. When the toxic compound is unknown, the diagnosis is based on epidemiology, clinical signs, clinical and anatomic pathology. Control methods include management practices, biologic control, conditioned food aversion, and integrated control strategies, whereas prophylactic approaches are mainly based on natural or induced resistance and preventive management practices. It is concluded that plant poisonings cause significant economic losses in livestock in South America. However, they are not sufficiently studied in several regions and countries of the continent and the creation of new research groups is necessary to improve the knowledge of poisonous plants.
{"title":"Toxic plants affecting livestock in South America: Review of epidemiology, diagnosis, control, economic impact and implications to human health1","authors":"Franklin Riet-Correa , Juan F. Micheloud , Mizael Machado , Fabio S. Mendonça , Ana Lucia Schild , Francisco A. Uzal , Ricardo A.A. Lemos","doi":"10.1016/j.toxicon.2026.108999","DOIUrl":"10.1016/j.toxicon.2026.108999","url":null,"abstract":"<div><div>The objective of this paper is to review the information on toxic plants for ruminants and horses in South America, a continent in which there are 237 plants known to be toxic for livestock. Predisposing factors for plant toxicity include parts or vegetative state of the plants consumed, sprouting after rains, toxic dose, social facilitation, palatability, hunger, thirst, naivete, ingestion period, susceptibility/resistance, transportation, climatic alterations, and environmental degradation. Toxic plants can be forage or non-forage species. The latter can be invasive plants from other regions or from the same region. For the diagnosis of plant poisoning caused by known active compounds, the detection of these substances in the plants and/or animals, coupled with clinical signs, clinical and anatomic pathology, is necessary to confirm the diagnosis. When the toxic compound is unknown, the diagnosis is based on epidemiology, clinical signs, clinical and anatomic pathology. Control methods include management practices, biologic control, conditioned food aversion, and integrated control strategies, whereas prophylactic approaches are mainly based on natural or induced resistance and preventive management practices. It is concluded that plant poisonings cause significant economic losses in livestock in South America. However, they are not sufficiently studied in several regions and countries of the continent and the creation of new research groups is necessary to improve the knowledge of poisonous plants.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"273 ","pages":"Article 108999"},"PeriodicalIF":2.4,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146019799","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 : 2026-01-16DOI: 10.1016/j.toxicon.2026.109000
Chenchen Song , Kesong Zhu , Yafei Zhuang , Hongyu Jia , Aimei Liu
Chronic exposure to deoxynivalenol (DON)-contaminated food and feed poses significant hepatotoxic, enterotoxic, and immunotoxic risks to humans and animals. Nuclear factor erythroid 2-related factor 2 (Nrf2), a crucial cellular protective factor, plays a pivotal role in oxidative stress, inflammatory responses, and apoptosis. This review demonstrates that modulation of the Nrf2 signaling pathway can mitigate oxidative damage, suppress inflammatory responses and ferroptosis, reduce apoptosis, and alleviate endoplasmic reticulum stress and DON-induced injury, thereby protecting organisms from DON toxicity. Nrf2-targeting agents—including plant extracts, proteins and amino acids, selenium, microbial preparations, and other nutrients—primarily exert protective effects by enhancing Nrf2 expression, promoting its nuclear translocation, and upregulating downstream target genes to counteract DON-induced organotoxicity. Notably, we identified a “threshold effect” of Nrf2 in DON toxicity: moderate oxidative stress activates Nrf2-mediated cytoprotection, whereas excessive oxidative stress suppresses Nrf2 and exacerbates damage. This threshold is a concentration- and context-dependent regulatory boundary jointly determined by DON-induced reactive oxygen species (ROS) burst intensity, Keap1-Nrf2 binding affinity, and downstream pathway integrity. Below the threshold, physiological ROS induces Keap1 conformational change and Nrf2 nuclear translocation; beyond it, excessive ROS impairs Nrf2 activation and triggers its degradation. This review provides novel insights into Nrf2-based therapeutic strategies, offering promising approaches to alleviate DON-induced organ toxicity.
{"title":"Nrf2: the key target for antagonizing the toxicity of deoxynivalenol","authors":"Chenchen Song , Kesong Zhu , Yafei Zhuang , Hongyu Jia , Aimei Liu","doi":"10.1016/j.toxicon.2026.109000","DOIUrl":"10.1016/j.toxicon.2026.109000","url":null,"abstract":"<div><div>Chronic exposure to deoxynivalenol (DON)-contaminated food and feed poses significant hepatotoxic, enterotoxic, and immunotoxic risks to humans and animals. Nuclear factor erythroid 2-related factor 2 (Nrf2), a crucial cellular protective factor, plays a pivotal role in oxidative stress, inflammatory responses, and apoptosis. This review demonstrates that modulation of the Nrf2 signaling pathway can mitigate oxidative damage, suppress inflammatory responses and ferroptosis, reduce apoptosis, and alleviate endoplasmic reticulum stress and DON-induced injury, thereby protecting organisms from DON toxicity. Nrf2-targeting agents—including plant extracts, proteins and amino acids, selenium, microbial preparations, and other nutrients—primarily exert protective effects by enhancing Nrf2 expression, promoting its nuclear translocation, and upregulating downstream target genes to counteract DON-induced organotoxicity. Notably, we identified a “threshold effect” of Nrf2 in DON toxicity: moderate oxidative stress activates Nrf2-mediated cytoprotection, whereas excessive oxidative stress suppresses Nrf2 and exacerbates damage. This threshold is a concentration- and context-dependent regulatory boundary jointly determined by DON-induced reactive oxygen species (ROS) burst intensity, Keap1-Nrf2 binding affinity, and downstream pathway integrity. Below the threshold, physiological ROS induces Keap1 conformational change and Nrf2 nuclear translocation; beyond it, excessive ROS impairs Nrf2 activation and triggers its degradation. This review provides novel insights into Nrf2-based therapeutic strategies, offering promising approaches to alleviate DON-induced organ toxicity.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"273 ","pages":"Article 109000"},"PeriodicalIF":2.4,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998866","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 : 2026-01-14DOI: 10.1016/j.toxicon.2025.108969
Haifeng Xu , Mátyás A. Bittenbinder , Julien Slagboom , Nicholas R. Casewell , Paul Jennings , Jeroen Kool
Cytotoxicity is a major pathological effect that can occur during snakebite envenoming. To better understand the underlying biochemical and molecular mechanisms behind snake venom-induced cytotoxicity, it is essential to use appropriate in vitro tools for bioassaying cytotoxicity evoked by snake venoms. Identifying the toxins causing cytotoxicity is also important in this regard, particularly in the context of developing more effective snakebite treatments. Cytotoxicity induced by venom toxins can result in local pathologies in snakebite victims, which can result in long-term morbidity, and is frequently observed after bites by medically important vipers. In the present study, we optimized and applied an analytical cytotoxicity profiling platform for in vitro cytotoxicity assessment of viper venoms. Using four cell lines (RPTEC/TERT1, HepaRG, iPSC-EC, HaCat), we applied an imaging analysis assay together with resazurin reduction to identify the mechanisms of cytotoxicity at the level of cell necrosis, extracellular matrix (ECM) degradation and/or cell apoptosis. Strong cytotoxic peaks are consistent with ECM-associated cytotoxic effects, as reflected by pronounced reductions in cell area and monolayer integrity. These cytotoxicity bioassays were integrated into nanofractionation analytics and high throughput venomics, which allowed for the identification of viper venom cytotoxins at the biological and chemical levels. Venom profiling showed ECM degradation as the main cytotoxic mechanism, except for Daboia russelii, which induced necrosis and apoptosis in three cell lines. Cytotoxicity largely disappeared after reversed-phase separation, prompting use of non-denaturing SEC in nanofractionation analytics, which revealed strong cytotoxic peaks for Bothrops jararaca and Calloselasma rhodostoma in RPTEC/TERT1 cells. The methodology presented here combined analytical and biochemical tools allowing rapid cytotoxicity profiling of viper venom toxins in parallel with toxin identification.
{"title":"Selectivity screening of cytotoxicity evoked by viper venoms and their toxins after nanofractionation","authors":"Haifeng Xu , Mátyás A. Bittenbinder , Julien Slagboom , Nicholas R. Casewell , Paul Jennings , Jeroen Kool","doi":"10.1016/j.toxicon.2025.108969","DOIUrl":"10.1016/j.toxicon.2025.108969","url":null,"abstract":"<div><div>Cytotoxicity is a major pathological effect that can occur during snakebite envenoming. To better understand the underlying biochemical and molecular mechanisms behind snake venom-induced cytotoxicity, it is essential to use appropriate <em>in vitro</em> tools for bioassaying cytotoxicity evoked by snake venoms. Identifying the toxins causing cytotoxicity is also important in this regard, particularly in the context of developing more effective snakebite treatments. Cytotoxicity induced by venom toxins can result in local pathologies in snakebite victims, which can result in long-term morbidity, and is frequently observed after bites by medically important vipers. In the present study, we optimized and applied an analytical cytotoxicity profiling platform for <em>in vitro</em> cytotoxicity assessment of viper venoms. Using four cell lines (RPTEC/TERT1, HepaRG, iPSC-EC, HaCat), we applied an imaging analysis assay together with resazurin reduction to identify the mechanisms of cytotoxicity at the level of cell necrosis, extracellular matrix (ECM) degradation and/or cell apoptosis. Strong cytotoxic peaks are consistent with ECM-associated cytotoxic effects, as reflected by pronounced reductions in cell area and monolayer integrity. These cytotoxicity bioassays were integrated into nanofractionation analytics and high throughput venomics, which allowed for the identification of viper venom cytotoxins at the biological and chemical levels. Venom profiling showed ECM degradation as the main cytotoxic mechanism, except for <em>Daboia russelii</em>, which induced necrosis and apoptosis in three cell lines. Cytotoxicity largely disappeared after reversed-phase separation, prompting use of non-denaturing SEC in nanofractionation analytics, which revealed strong cytotoxic peaks for <em>Bothrops jararaca</em> and <em>Calloselasma rhodostoma</em> in RPTEC/TERT1 cells. The methodology presented here combined analytical and biochemical tools allowing rapid cytotoxicity profiling of viper venom toxins in parallel with toxin identification.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"273 ","pages":"Article 108969"},"PeriodicalIF":2.4,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145990900","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 : 2026-01-13DOI: 10.1016/j.toxicon.2026.108997
Luiza Spinola Gabriel , Eduardo Oliveira Venancio de Lima , Pedro Henrique Tavares Perrotti , Lucas de Carvalho Francisco Alves , Anita Mitico Tanaka-Azevedo
Snakebite envenomation is a neglected tropical disease affecting thousands of people globally, especially in tropical and subtropical regions. An estimated 81,000 to 138,000 deaths occur annually, with many survivors experiencing permanent disabilities. In Brazil, around 26,000 cases are reported each year, with the genus Bothrops responsible for 83.8 % of them. Bothrops venoms are rich in metalloproteases, serine proteases, phospholipases A2, and L-amino acid oxidases, which can cause hemorrhage, tissue necrosis, coagulation disorders, and hypotension. This study focuses on the biochemical and toxicological characterization of Bothrops fonsecai venom, an understudied and near-threatened species endemic to southeastern Brazil, not included in the venom pool for antibotropic serum preparation. Venoms from male and female specimens maintained at the Butantan Institute were compared using standard biochemical, enzymatic, immunological assays, and protein composition. Females tented to exhibited higher enzymatic activity than males in nearly all tests performed. Significant differences were found in EC50 values for indirect hemolysis and in the minimum coagulant dose, also indicating sex-based variation in venom potency. SDS-PAGE and RP-HPLC analyses revealed qualitative and quantitative differences in protein composition between sexes and individually. Immunological assays (ELISA and Western Blotting) demonstrated good immune recognition patterns, with only a few exceptions, which may reflect intraspecific variability in venom antigenicity. Although some biochemical information on Bothrops fonsecai is available, studies remain scarce and fragmented. This work advances current knowledge by providing a broader characterization of the venom and by examining intraspecific patterns—such as sex-related and individual variation—that had not been previously explored in an integrated way. These findings contribute to a more complete understanding of the species, which is especially relevant given its limited representation in venom research and may contribute to improving the effectiveness of antivenom therapies and clinical management of envenomations caused by this species.
{"title":"Comparative analyses of Bothrops fonsecai snake venom: individual variability and sex-based differences","authors":"Luiza Spinola Gabriel , Eduardo Oliveira Venancio de Lima , Pedro Henrique Tavares Perrotti , Lucas de Carvalho Francisco Alves , Anita Mitico Tanaka-Azevedo","doi":"10.1016/j.toxicon.2026.108997","DOIUrl":"10.1016/j.toxicon.2026.108997","url":null,"abstract":"<div><div>Snakebite envenomation is a neglected tropical disease affecting thousands of people globally, especially in tropical and subtropical regions. An estimated 81,000 to 138,000 deaths occur annually, with many survivors experiencing permanent disabilities. In Brazil, around 26,000 cases are reported each year, with the genus <em>Bothrops</em> responsible for 83.8 % of them. <em>Bothrops</em> venoms are rich in metalloproteases, serine proteases, phospholipases A<sub>2</sub>, and L-amino acid oxidases, which can cause hemorrhage, tissue necrosis, coagulation disorders, and hypotension. This study focuses on the biochemical and toxicological characterization of <em>Bothrops fonsecai</em> venom, an understudied and near-threatened species endemic to southeastern Brazil, not included in the venom pool for antibotropic serum preparation. Venoms from male and female specimens maintained at the Butantan Institute were compared using standard biochemical, enzymatic, immunological assays, and protein composition. Females tented to exhibited higher enzymatic activity than males in nearly all tests performed. Significant differences were found in EC<sub>50</sub> values for indirect hemolysis and in the minimum coagulant dose, also indicating sex-based variation in venom potency. SDS-PAGE and RP-HPLC analyses revealed qualitative and quantitative differences in protein composition between sexes and individually. Immunological assays (ELISA and Western Blotting) demonstrated good immune recognition patterns, with only a few exceptions, which may reflect intraspecific variability in venom antigenicity. Although some biochemical information on <em>Bothrops fonsecai</em> is available, studies remain scarce and fragmented. This work advances current knowledge by providing a broader characterization of the venom and by examining intraspecific patterns—such as sex-related and individual variation—that had not been previously explored in an integrated way. These findings contribute to a more complete understanding of the species, which is especially relevant given its limited representation in venom research and may contribute to improving the effectiveness of antivenom therapies and clinical management of envenomations caused by this species.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"273 ","pages":"Article 108997"},"PeriodicalIF":2.4,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145990865","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 : 2026-01-13DOI: 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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号