IF 4 3区医学

Toxins Pub Date : 2025-09-04 DOI: 10.3390/toxins17090443

Chiyono Morimoto, Sho Amatsu, Takuhiro Matsumura, Masahiko Zuka, Yukako Fujinaga

{"title":"Botulinum Toxin Complex Serotype B-Okra Exerts Systemic Toxicity via the Oral Route by Disrupting the Intestinal Epithelial Barrier.","authors":"Chiyono Morimoto, Sho Amatsu, Takuhiro Matsumura, Masahiko Zuka, Yukako Fujinaga","doi":"10.3390/toxins17090443","DOIUrl":"10.3390/toxins17090443","url":null,"abstract":"Botulinum toxin (BoNT) causes flaccid paralysis by blocking the release of neurotransmitters. BoNTs associate with neurotoxin-associated proteins to form medium and large progenitor toxin complexes. The large progenitor toxin complex serotype A-62A (L-PTC/A-62A) specifically targets intestinal M cells for invasion, whereas large progenitor toxin complex serotype B-Okra (L-PTC/B-Okra) is mainly taken up by enterocytes and exhibits higher toxicity via the oral route. Hemagglutinin (HA) is a neurotoxin-associated protein that promotes BoNT absorption from the intestine and has carbohydrate-binding and barrier-disrupting activities. In this study, we established an in vitro reconstitution and purification system for recombinant L-PTC/B-Okra and created a recombinant L-PTC/B-Okra mutant rL-PTC/B-KA with carbohydrate-binding activity but not barrier-disrupting activity. rL-PTC/B-KA showed significantly reduced oral toxicity. Our results demonstrate that the B-Okra toxin disrupts the epithelial barrier of enterocytes and exerts oral toxicity.","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intermittent Infusion Hemodiafiltration: A Narrative Review of an Emerging Dialysis Modality. 间歇输注血液滤过：一种新兴透析方式的叙述性回顾。

IF 4 3区医学

Toxins Pub Date : 2025-09-03 DOI: 10.3390/toxins17090442

Xiaoxi Zhou, Jing Sun, Lining Miao

{"title":"Intermittent Infusion Hemodiafiltration: A Narrative Review of an Emerging Dialysis Modality.","authors":"Xiaoxi Zhou, Jing Sun, Lining Miao","doi":"10.3390/toxins17090442","DOIUrl":"10.3390/toxins17090442","url":null,"abstract":"The number of patients with end-stage renal disease continues to grow worldwide, placing increasing demands on dialysis technologies. Conventional hemodialysis remains the dominant modality but is often limited by frequent intradialytic hypotension and the insufficient removal of medium-sized toxins. Intermittent infusion hemodiafiltration (I-HDF) is an emerging, hybrid dialysis technique that combines standard hemodialysis with the cyclic backfiltration of ultrapure dialysate. This approach enables dynamic blood volume control and periodic backflushing of the dialyzer membrane. Recent clinical studies demonstrate that I-HDF can reduce intradialytic hypotension incidence, improve systemic and microcirculatory perfusion, and enhance the clearance of middle molecules such as β2-microglobulin, while minimizing albumin loss. These benefits are particularly relevant to toxin clearance and hemodynamic stabilization, key priorities in optimizing dialysis outcomes. Large-scale cohort data suggest that I-HDF may be linked to improved long-term survival in dialysis patients. Given its physiological advantages and operational flexibility, I-HDF may also offer a practical solution in healthcare systems with limited access to high-volume online hemodiafiltration or kidney transplantation. Further research is warranted to develop individualized infusion protocols and validate its broader applicability.","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic Characterization of Staphylococcus aureus Isolates Associated with Toxic Shock Syndrome Toxin Production: An Epidemiological and Bioinformatics Approach. 与中毒性休克综合征毒素产生相关的金黄色葡萄球菌分离株的遗传特征：流行病学和生物信息学方法。

IF 4 3区医学

Toxins Pub Date : 2025-09-03 DOI: 10.3390/toxins17090440

J R Aguirre-Sánchez, C Chaidez-Quiroz, Nohemi Castro-Del Campo, Nohelia Castro-Del Campo

{"title":"Genetic Characterization of Staphylococcus aureus Isolates Associated with Toxic Shock Syndrome Toxin Production: An Epidemiological and Bioinformatics Approach.","authors":"J R Aguirre-Sánchez, C Chaidez-Quiroz, Nohemi Castro-Del Campo, Nohelia Castro-Del Campo","doi":"10.3390/toxins17090440","DOIUrl":"10.3390/toxins17090440","url":null,"abstract":"Staphylococcus aureus is an opportunistic pathogen, a member of the ESKAPE group, associated with nosocomial infections and foodborne illnesses due to its production of various toxins. This study conducted a comprehensive genomic characterization of S. aureus isolates producing toxic shock syndrome toxin (TSST-1) using a comparative genomics and bioinformatics approach. A total of 166, including 3 bovine mastitis isolates and 163 public genomes, were analyzed. Twenty-eight distinct sequence types (STs) were identified, with ST30 and ST5 being the most prevalent, corresponding to the clonal complexes CC30 and CC5, respectively. Phylogenetic reconstruction revealed two major clades aligned with these complexes, each exhibiting unique virulence factor profiles. Notably, TSST-1 was detected in bovine mastitis genomes, alongside a broad repertoire of virulence markers, such as enterotoxins and secretion system components, posing a potential risk to public health. Additionally, genes related to environmental information processing systems, including ABC transporters and phosphotransferase systems, were prevalent. These results underscore the need for strengthened genomic surveillance and the implementation of both preventive and corrective measures in dairy herds to mitigate zoonotic transmission and ensure food safety.","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Preliminary Assessment of Alkaloid Content in Cocoa (Theobroma cacao L.) Hulls for Safe Consumption as a Feed Ingredient. 可可（Theobroma Cocoa L.）生物碱含量的初步评价作为饲料原料安全食用的船壳。

IF 4 3区医学

Toxins Pub Date : 2025-09-03 DOI: 10.3390/toxins17090441

Francesca Mercogliano, Corinne Bani, Marco Tretola, Carla Landolfi, Matteo Ottoboni, Federica Cheli, Patrizia Restani, Luciano Pinotti, Chiara Di Lorenzo

{"title":"Preliminary Assessment of Alkaloid Content in Cocoa (Theobroma cacao L.) Hulls for Safe Consumption as a Feed Ingredient.","authors":"Francesca Mercogliano, Corinne Bani, Marco Tretola, Carla Landolfi, Matteo Ottoboni, Federica Cheli, Patrizia Restani, Luciano Pinotti, Chiara Di Lorenzo","doi":"10.3390/toxins17090441","DOIUrl":"10.3390/toxins17090441","url":null,"abstract":"The European Circular Economy Action Plan outlines a forward-looking strategy that emphasizes waste reduction and the acquisition of high-quality secondary resources. Previous research has shown that cocoa processing by-products contain compounds of interest for various industrial areas, making them an attractive matrix for reuse. However, a gap remains in our understanding of the safety of these by-products intended for feed. In this study, theobromine and caffeine were quantified by High-Performance Liquid Chromatography (HPLC-UV) in cocoa hulls for safety considerations, evaluating theobromine compliance with toxicological and safety levels, and considering their potential application as an ingredient in animal feed. In addition, the identification of phenolic components and associated antioxidant activity was conducted through High-Performance Thin-Layer Chromatography (HPTLC). This preliminary study indicates that theobromine content is a limiting factor for the inclusion of cocoa hulls in animal diets, as it restricts inclusion levels to remain within current regulatory limits. Examples of general estimates of dietary theobromine exposure at inclusion levels based on regulatory limits for dairy cows and veal calves confirmed a low risk for animal health. Furthermore, the detection of antioxidant activity linked to the presence of polyphenols highlights the potential of cocoa hulls as a sustainable food by-product for feed formulation.","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neurotoxicity of Sri Lankan Krait (Bungarus ceylonicus) and Common Krait (Bungarus caeruleus) Venoms and Their Neutralisation by Commercial Antivenoms In Vitro. 斯里兰卡河鼠（Bungarus ceylonicus）和普通河鼠（Bungarus caeruleus）毒液的神经毒性及其体外抗蛇毒血清的中和作用。

IF 4 3区医学

Toxins Pub Date : 2025-09-02 DOI: 10.3390/toxins17090439

Jithmi Galappaththige, Geoffrey K Isbister, Kalana Maduwage, Wayne C Hodgson, Anjana Silva

{"title":"Neurotoxicity of Sri Lankan Krait (Bungarus ceylonicus) and Common Krait (Bungarus caeruleus) Venoms and Their Neutralisation by Commercial Antivenoms In Vitro.","authors":"Jithmi Galappaththige, Geoffrey K Isbister, Kalana Maduwage, Wayne C Hodgson, Anjana Silva","doi":"10.3390/toxins17090439","DOIUrl":"10.3390/toxins17090439","url":null,"abstract":"The common krait (Bungarus caeruleus) and the endemic Sri Lankan krait (B. ceylonicus) are two species of krait responsible for envenomings in Sri Lanka that result in progressive neuromuscular paralysis. We characterised the in vitro neurotoxicity of B. ceylonicus and B. caeruleus venoms and studied their neutralisation by two commercially available Indian polyvalent antivenoms (i.e., VINS and BHARAT), Thai banded krait antivenom and Australian polyvalent antivenom using the chick biventer cervicis nerve-muscle preparation. Both venoms displayed concentration-dependent neurotoxicity, showing equipotent pre-synaptic neurotoxicity at 0.03 μg/mL. At a higher concentration (1 μg/mL), both venoms showed post-synaptic neurotoxicity, with B. ceylonicus venom being more potent. VINS was unable to neutralise the neurotoxicity of B. ceylonicus venom, but neutralised both pre- and post-synaptic neurotoxicity of B. caeruleus venom. BHARAT neutralised in vitro pre- and post-synaptic activity of both B. ceylonicus and B. caeruleus venoms. Banded krait antivenom and Australian polyvalent antivenoms were unable to fully neutralise the neurotoxicity of either venom at tested concentrations. In conclusion, B. ceylonicus venom shows pre- and post-synaptic neurotoxicity similar to B. caeruleus venom. BHARAT effectively neutralises both pre- and post-synaptic neurotoxicity of B. ceylonicus venom. Both Indian polyvalent antivenoms effectively neutralise neurotoxicity induced by B. caeruleus venom.","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biocatalytic Detoxification of Ochratoxins A/B by a Fungal Dye-Decolorizing Peroxidase: Mechanistic Insights and Toxicity Assessment. 真菌染料脱色过氧化物酶对赭曲霉毒素A/B的生物催化解毒作用：机理和毒性评估。

IF 4 3区医学

Toxins Pub Date : 2025-09-02 DOI: 10.3390/toxins17090438

Wenjing Xia, Nianqing Zhu, Jie Mei, Yueqin Peng, Fanglin Song, Shuai Ding, Fei Li, Xue Zhou

{"title":"Biocatalytic Detoxification of Ochratoxins A/B by a Fungal Dye-Decolorizing Peroxidase: Mechanistic Insights and Toxicity Assessment.","authors":"Wenjing Xia, Nianqing Zhu, Jie Mei, Yueqin Peng, Fanglin Song, Shuai Ding, Fei Li, Xue Zhou","doi":"10.3390/toxins17090438","DOIUrl":"10.3390/toxins17090438","url":null,"abstract":"Mycotoxin contamination in agricultural products poses severe global health risks, with ochratoxins (particularly OTA and OTB) exhibiting marked nephrotoxicity and classified as Group 2B carcinogens by IARC. Conventional physical/chemical detoxification methods often impair food nutritional quality, highlighting the need for enzymatic alternatives. Herein, we systematically investigated the degradation mechanisms of ochratoxin A (OTA) and ochratoxin B (OTB) using Pleurotus ostreatus dye-decolorizing peroxidase (PoDyP4) coupled with redox mediators. Remarkably, hydroxybenzotriazole (HBT) enhanced degradation efficiency 26.7-fold for OTA and 10.6-fold for OTB compared to mediator-free systems, establishing it as the optimal catalytic enhancer. Through LC-MS/MS analysis, we identified five key degradation products, including 6-OH-OTA and OTB-quinone, elucidating a putative oxidative degradation pathway. In vitro cytotoxicological evaluation in HK-2 cells demonstrated that PoDyP4-treated ochratoxins significantly attenuated cytotoxicity, reducing malondialdehyde (MDA) levels by 48.7% (OTA) and 42.3% (OTB) (p < 0.01) and suppressing ROS generation. Molecular docking revealed strong binding affinities between PoDyP4 and ochratoxins, with calculated binding energies of -7.6 kcal/mol (OTA) and -8.6 kcal/mol (OTB), stabilized by hydrogen bond networks (1.9-3.4 Å). These findings position PoDyP4 as a promising biocatalyst for mycotoxin mitigation in food systems, offering a sustainable alternative to traditional detoxification methods.","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Toxicity Profiling and In Vivo Metabolism of Danshensu-Derived Novel Antihypertensive Candidate 221s (2,9). 丹参素衍生的新型抗高血压候选药物221s的毒性分析和体内代谢（2,9）。

IF 4 3区医学

Toxins Pub Date : 2025-09-01 DOI: 10.3390/toxins17090436

Yunmei Chen, Kuan Yang, Lili Yu, Rong Wang, Shaojing Liu, Bei Qin

{"title":"Toxicity Profiling and In Vivo Metabolism of Danshensu-Derived Novel Antihypertensive Candidate 221s (2,9).","authors":"Yunmei Chen, Kuan Yang, Lili Yu, Rong Wang, Shaojing Liu, Bei Qin","doi":"10.3390/toxins17090436","DOIUrl":"10.3390/toxins17090436","url":null,"abstract":"Compound 221s (2,9) is a novel antihypertensive drug candidate synthesized utilizing danshensu, borneol, and proline by using the strategy of combinatorial molecular chemistry. This study aimed to systematically identify the safety of danshensu-derived compound 221s (2,9) by conducting an acute toxicity test and long-term toxicity study and to elucidate the in vivo metabolic pathways of 221s (2,9) in order to provide critical insights into the observed toxicity. In the acute toxicity study, a single oral dose of 221s (2,9) at 3000 mg/kg in mice produced no clinical signs of toxicity or mortality, indicating an MTD of 3000 mg/kg. In a subsequent 12-week repeated-dose toxicity study in rats, doses of 20, 40, and 80 mg/kg were well tolerated, with no adverse clinical observations or deaths. Notably, organ coefficient analysis revealed transient lung injury, which resolved following a 4-week recovery period. The metabolite identification study indicated that metabolism in rats is predominated by Phase II metabolites, potentially contributing to the low toxicity of 221s (2,9). Further investigation into the impact of the drug metabolic enzyme-transporter interplay on the in vivo disposition of 221s (2,9) is warranted.","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction: Sławek et al. Case Series and Literature Review on Botulinum Toxin Efficacy in Axial Extensor Truncal Dystonia. Toxins 2025, 17, 375. 更正：Sławek等。肉毒杆菌毒素治疗轴伸肌-躯干肌张力障碍的病例分析及文献综述。毒素2025,17,375。

IF 4 3区医学

Toxins Pub Date : 2025-09-01 DOI: 10.3390/toxins17090435

Jarosław Sławek, Iga Alicja Łobińska, Michał Schinwelski, Joanna Kopcewicz-Wiśniewska, Anna Castagna

引用次数: 0

Ultrasound-Guided Multi-Branch Rectus Femoris Nerve Block for Spasticity Assessment. 超声引导下股直肌多支神经阻滞用于痉挛评估。

IF 4 3区医学

Toxins Pub Date : 2025-09-01 DOI: 10.3390/toxins17090437

Stefano Carda, Elisa Grana, Thierry Deltombe, Rajiv Reebye

{"title":"Ultrasound-Guided Multi-Branch Rectus Femoris Nerve Block for Spasticity Assessment.","authors":"Stefano Carda, Elisa Grana, Thierry Deltombe, Rajiv Reebye","doi":"10.3390/toxins17090437","DOIUrl":"10.3390/toxins17090437","url":null,"abstract":"Background: Stiff-knee gait commonly involves rectus femoris spasticity in patients with central nervous system lesions. Diagnostic nerve blocks aid in predicting treatment outcomes; however, current techniques may overlook multiple nerve branches that innervate the rectus femoris muscle, potentially resulting in an incomplete assessment of treatment outcomes. Methods: We present an ultrasound-guided approach that we currently use in our practice, using anatomical landmarks, including the femoral artery, the sartorius muscle, and the rectus femoris' characteristic \"J-shaped\" internal tendon. The technique employs an \"elevator\" scanning method to identify all motor nerve branches (typically 2-3) entering the proximal third of the rectus femoris muscle. Each branch is blocked using an in-plane needle approach with 1-2 mL of 2% lidocaine. Results: The technique enables the visualization of hyperechoic nerve branches entering the rectus femoris muscle from medial to lateral, sometimes accompanied by small vascular branches that are identifiable with a Doppler ultrasound. Optimal ultrasound settings include probes >8 MHz, appropriate focus positioning, and dynamic range < 60 dB. The multi-branch approach produces rapid-onset motor weakness (5-10 min). Conclusions: This comprehensive multi-branch rectus femoris nerve block technique may enhance diagnostic accuracy for spasticity assessment, potentially leading to more informed treatment selection for stiff-knee gait.","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

From Uremic Toxins to Hemodialysis Access Failure: IL-8 and MCP-1 Chemokines as a Link Between Endothelial Activation and AV Access Complications. 从尿毒症毒素到血液透析通路失败：IL-8和MCP-1趋化因子在内皮活化和AV通路并发症之间的联系

IF 4 3区医学

Toxins Pub Date : 2025-08-31 DOI: 10.3390/toxins17090434

Rania Chermiti, Stanislas Bataille, Philippe Giaime, Justine Solignac, Nathalie Pedinielli, Nathalie McKay, Dorian Bigey-Frau, Guillaume Lano, Hamza Benjelloun, Tawfik Addi, Julien Mancini, Stéphane Burtey, Laetitia Dou

{"title":"From Uremic Toxins to Hemodialysis Access Failure: IL-8 and MCP-1 Chemokines as a Link Between Endothelial Activation and AV Access Complications.","authors":"Rania Chermiti, Stanislas Bataille, Philippe Giaime, Justine Solignac, Nathalie Pedinielli, Nathalie McKay, Dorian Bigey-Frau, Guillaume Lano, Hamza Benjelloun, Tawfik Addi, Julien Mancini, Stéphane Burtey, Laetitia Dou","doi":"10.3390/toxins17090434","DOIUrl":"10.3390/toxins17090434","url":null,"abstract":"Arteriovenous (AV) access complications remain a major cause of morbidity in hemodialysis patients, influenced by multiple factors, including endothelial inflammation induced by uremia. In this study, we investigated the mechanisms underlying the upregulation of endothelial chemokines interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) by indolic uremic toxins, as well as their association with AV access complications in hemodialysis patients. In cultured human endothelial cells, IL-8 and MCP-1 were upregulated by indolic uremic toxins through activation of their receptor, the aryl hydrocarbon receptor (AHR), and non-canonical TGF-β pathway involving TAK1/p38 MAPK/AP-1 signaling. In a retrospective observational study of 204 hemodialysis patients, baseline serum IL-8 or MCP-1 were positively correlated with indolic uremic toxins and TGFβ1. Additionally, serum IL-8 ≥ 40.26 pg/mL and serum MCP-1 were independently associated with an increased risk of AV access complications over a 2-year period. In conclusion, we demonstrated that indolic uremic toxins promote endothelial inflammation by inducing IL-8 and MCP-1 expression via AHR activation and non-canonical TGF-β signaling. Clinically, elevated serum IL-8 and MCP-1 were independently associated with an increased risk of AV access complications in hemodialysis patients.","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Toxins最新文献