Pub Date : 2026-04-01Epub 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":"2026-04-01","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 : 2026-04-01Epub 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":"2026-04-01","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 : 2026-04-01Epub 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":"2026-04-01","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 : 2026-04-01Epub 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":"2026-04-01","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 : 2026-04-01Epub 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":"2026-04-01","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 : 2026-04-01Epub 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":"2026-04-01","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 : 2026-04-01Epub 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":"2026-04-01","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}
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":"2026-04-01","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}
Pub Date : 2026-03-21DOI: 10.1016/j.toxicon.2026.109085
Dan Yu, Qing Sun, Wensai Ji, Ying Chen, Xiaoli Wu, Yingzi Chen, Xiaoyu Hua, Zengliang Ruan, Liang Xiao
Marine organism injuries constitute a persistent occupational hazard for fishermen, yet epidemiological data describing their occurrence and determinants remain limited. We conducted a cross-sectional survey among 943 fishermen in coastal areas of Fujian Province, China, between July 2023 and July 2024 to assess injury prevalence, clinical manifestations, and associated risk factors. Injury history was reported by all participants, with nearly half (44.11%) experiencing medium-frequency injuries (4-6 episodes). Stingrays, jellyfish, and echinoderms were the most commonly reported causative organisms. Local manifestations were predominantly characterized by burning sensation, numbness, and pain, while myalgia was the most frequently reported systemic symptom. Sequelae were reported by the majority of injured fishermen. Fishing net repair showed a significant exposure-response relationship with injury frequency. Mariculture, seafood retail, vessel equipment maintenance and repair, and working while sick were identified as independent risk factors for high-frequency injuries (7-10 episodes). Working in shallow waters (OR = 0.63) and during April-June (OR = 0.24) were associated with a lower risk of medium-frequency injuries, while working during October-December (OR = 0.24) reduced the risk of high-frequency injuries. These findings highlight the substantial burden and recurrence of marine organism injuries among fishermen in Fujian Province and underscore the need for coordinated preventive measures integrating occupational safety management, targeted health education, and accessible medical support.
{"title":"Prevalence and Associated Risk Factors of Marine Organism Injuries among Fishermen in Coastal Fujian, China.","authors":"Dan Yu, Qing Sun, Wensai Ji, Ying Chen, Xiaoli Wu, Yingzi Chen, Xiaoyu Hua, Zengliang Ruan, Liang Xiao","doi":"10.1016/j.toxicon.2026.109085","DOIUrl":"https://doi.org/10.1016/j.toxicon.2026.109085","url":null,"abstract":"<p><p>Marine organism injuries constitute a persistent occupational hazard for fishermen, yet epidemiological data describing their occurrence and determinants remain limited. We conducted a cross-sectional survey among 943 fishermen in coastal areas of Fujian Province, China, between July 2023 and July 2024 to assess injury prevalence, clinical manifestations, and associated risk factors. Injury history was reported by all participants, with nearly half (44.11%) experiencing medium-frequency injuries (4-6 episodes). Stingrays, jellyfish, and echinoderms were the most commonly reported causative organisms. Local manifestations were predominantly characterized by burning sensation, numbness, and pain, while myalgia was the most frequently reported systemic symptom. Sequelae were reported by the majority of injured fishermen. Fishing net repair showed a significant exposure-response relationship with injury frequency. Mariculture, seafood retail, vessel equipment maintenance and repair, and working while sick were identified as independent risk factors for high-frequency injuries (7-10 episodes). Working in shallow waters (OR = 0.63) and during April-June (OR = 0.24) were associated with a lower risk of medium-frequency injuries, while working during October-December (OR = 0.24) reduced the risk of high-frequency injuries. These findings highlight the substantial burden and recurrence of marine organism injuries among fishermen in Fujian Province and underscore the need for coordinated preventive measures integrating occupational safety management, targeted health education, and accessible medical support.</p>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":" ","pages":"109085"},"PeriodicalIF":2.4,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504999","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 : 2026-03-20DOI: 10.1016/j.toxicon.2026.109073
D De Monte, G M Squintani, G Ermanis, F Lavezzi, S Flumignan, G Valiante, B H Ercole, E Belgrado, A Bernardini, Y Tereshko, M Valente, S Rossi, C Lettieri
Multiple System Atrophy (MSA) is a progressive neurodegenerative disorder characterized by autonomic dysfunction, parkinsonism, and cerebellar signs. Among its motor manifestations, camptocormia-defined as an abnormal forward flexion of the trunk-often emerges early in the disease course and significantly compromises patients' quality of life. Aside from physical therapy, the treatment of camptocormia remains particularly challenging, especially in MSA, where surgical approaches such as deep brain stimulation and spinal cord stimulation are generally contraindicated. This underscores the urgent need for effective, non-invasive therapeutic strategies. We report a case of MSA presenting with early-onset and severe camptocormia, who underwent sequential treatment with three non-invasive interventions: subcutaneous apomorphine injection, repetitive trans-spinal magnetic stimulation (rTMS), and botulinum neurotoxin (BoNT) injections targeting the abdominal muscles. We aimed to evaluate and compare the efficacy of each intervention using standardized clinical rating scales, instrumented gait analysis, and static posturography. All three interventions resulted in partial improvements, though with varying degrees of efficacy. Subcutaneous apomorphine injection improved walking velocity and step length but was limited by adverse effects (nausea and hypotension), which precluded the use of continuous subcutaneous infusion as a long-term therapeutic option. Spinal rTMS enhanced performance on the Timed Up and Go (TUG) test, particularly during the return phase, but had no significant effect on posture-related measures. BoNT treatment yielded the most substantial improvements in both walking velocity and step length. Moreover, it was the only intervention to improve the posture item of the Unified Multiple System Atrophy Rating Scale (UMSARS) part II. This case underscores the importance of an integrated therapeutic approach in managing camptocormia, emphasizing the role of neurophysiological and biomechanical assessments in identifying biomarkers of therapeutic response and evaluating the efficacy of treatments such as BoNT and neuromodulation.
{"title":"Effects of apomorphine, spinal rTMS, and BoNT on camptocormia: an exploratory wearable sensor-based analysis in a patient with MSA.","authors":"D De Monte, G M Squintani, G Ermanis, F Lavezzi, S Flumignan, G Valiante, B H Ercole, E Belgrado, A Bernardini, Y Tereshko, M Valente, S Rossi, C Lettieri","doi":"10.1016/j.toxicon.2026.109073","DOIUrl":"https://doi.org/10.1016/j.toxicon.2026.109073","url":null,"abstract":"<p><p>Multiple System Atrophy (MSA) is a progressive neurodegenerative disorder characterized by autonomic dysfunction, parkinsonism, and cerebellar signs. Among its motor manifestations, camptocormia-defined as an abnormal forward flexion of the trunk-often emerges early in the disease course and significantly compromises patients' quality of life. Aside from physical therapy, the treatment of camptocormia remains particularly challenging, especially in MSA, where surgical approaches such as deep brain stimulation and spinal cord stimulation are generally contraindicated. This underscores the urgent need for effective, non-invasive therapeutic strategies. We report a case of MSA presenting with early-onset and severe camptocormia, who underwent sequential treatment with three non-invasive interventions: subcutaneous apomorphine injection, repetitive trans-spinal magnetic stimulation (rTMS), and botulinum neurotoxin (BoNT) injections targeting the abdominal muscles. We aimed to evaluate and compare the efficacy of each intervention using standardized clinical rating scales, instrumented gait analysis, and static posturography. All three interventions resulted in partial improvements, though with varying degrees of efficacy. Subcutaneous apomorphine injection improved walking velocity and step length but was limited by adverse effects (nausea and hypotension), which precluded the use of continuous subcutaneous infusion as a long-term therapeutic option. Spinal rTMS enhanced performance on the Timed Up and Go (TUG) test, particularly during the return phase, but had no significant effect on posture-related measures. BoNT treatment yielded the most substantial improvements in both walking velocity and step length. Moreover, it was the only intervention to improve the posture item of the Unified Multiple System Atrophy Rating Scale (UMSARS) part II. This case underscores the importance of an integrated therapeutic approach in managing camptocormia, emphasizing the role of neurophysiological and biomechanical assessments in identifying biomarkers of therapeutic response and evaluating the efficacy of treatments such as BoNT and neuromodulation.</p>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":" ","pages":"109073"},"PeriodicalIF":2.4,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499641","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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