Toxicon最新文献

{"title":"Plasma Metabolomics Analysis Reveals Potential Metabolic Biomarkers for Predicting Mushroom Poisoning.","authors":"Yuanping Gu, Hao Cui, Zhuange Shi, Hao Jia, Yifan Wang, Siyuan Huang, Xiulin Zhang, Jing Han, Hongmei Wang, Xiao Chen, Guobing Chen, Jiangping Song","doi":"10.1016/j.toxicon.2025.108591","DOIUrl":"https://doi.org/10.1016/j.toxicon.2025.108591","url":null,"abstract":"<p><p>The diagnosis of mushroom poisoning (MP) typically relies on patient-reported symptoms and biochemical indicators. However, when patients are in the early stage of poisoning or present with atypical clinical manifestations, traditional diagnostic methods become difficult. Metabolic biomarkers may play a key role in individualized monitoring and early detection. This study aims to identify biomarkers associated with MP using metabolomics to support early clinical diagnosis. Plasma samples were collected from 58 MP patients, 30 healthy controls (HC), and 25 patients with severe traumatic infections (SI). A non-targeted metabolomics analysis was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS), detecting 1,142 metabolites. Various statistical methods were applied to identify differential metabolites and analyze their correlations with clinical biochemical indicators. Plasma metabolomics analysis revealed significant metabolic differences between MP patients and both HC and SI groups. In total, 34 differential metabolites were identified between MP and HC, and 91 between MP and SI, while 112 differential metabolites were found between SI and HC. Metabolic abnormalities in MP patients were mainly related to cell membrane damage, oxidative stress, inflammatory responses, and lipid metabolism disorders. Among the three groups, 11 metabolites were significantly upregulated and 4 significantly downregulated in MP patients. Notably, four metabolites exhibited excellent predictive capabilities, with AUC values all exceeding 0.9, demonstrating strong discriminatory power for MP. This study identified several metabolites strongly associated with MP, including 5-Oxo-L-norvaline, L-Ergothioneine, Valylvaline, and 2-Arachidonyl Glycerol Ether. These biomarkers demonstrated outstanding predictive performance, providing crucial evidence to support the early diagnosis of mushroom poisoning. This study did not classify mushroom poisoning by type, but used a general analysis method. Whether this approach is useful in practice needs further study.</p>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":" ","pages":"108591"},"PeriodicalIF":2.4,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network toxicology and cell experiments reveal the mechanism of saikochromone A-induced hepatotoxicity","authors":"Ying Zhang,&nbsp;Fengmei Li,&nbsp;Xiang Ji,&nbsp;Limin Shao,&nbsp;Qian Lyu,&nbsp;Qi Shao","doi":"10.1016/j.toxicon.2025.108588","DOIUrl":"10.1016/j.toxicon.2025.108588","url":null,"abstract":"<div><div>The potential toxicity of traditional Chinese medicine (TCM) remains a significant barrier to its broader clinical application. <em>Bupleurum</em>, a commonly used TCM, contains saponins and volatile oils that have been shown to cause hepatotoxicity. Due to the complex chemical composition of <em>Bupleurum</em>, saikochromone A (SA), another major bioactive component, has not been thoroughly assessed in terms of its toxicological profile and underlying mechanisms. Our study aimed to evaluate the potential hepatotoxic effects of SA by integrating network toxicology, molecular docking analysis, and in vitro experimental approaches. A total of 109 possible targets associated with SA-induced hepatotoxicity were identified through the publicly available online databases. Functional enrichment analysis revealed significant involvement of pathways related to chemical carcinogenesis (DNA adducts) and cytochrome P450-mediated metabolism. Molecular docking simulations further demonstrated strong binding affinities between SA and key proteins, including CYP2E1, CYP1A1, CYP3A4, PTGS2, and MMP-9. In vitro experiments showed that SA significantly reduced cell viability, with an IC50 value of 176.8 μM. Additionally, SA exposure was found to upregulate the expression levels of CYP2E1, CYP1A1, CYP3A4, PTGS2, and MMP-9. By combining computational and experimental methodologies, this study systematically elucidates, for the first time, that high concentrations of SA may induce hepatotoxicity primarily through the CYP450 enzyme system, inflammatory pathway, and matrix metalloproteinase activation. These findings offer a novel methodological framework for identifying and evaluating toxic components in TCM and contribute valuable insights into the potential adverse effects of TCM in clinical practice.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"267 ","pages":"Article 108588"},"PeriodicalIF":2.4,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First report of microcystin-producing benthic cyanobacteria in Mexican mountain rivers: polyphasic characterization and HPLC toxin detection","authors":"Kenia Márquez-Santamaria ,&nbsp;Javier Carmona-Jiménez ,&nbsp;Angela Caro-Borrero ,&nbsp;Itzel Becerra-Absalón ,&nbsp;Macarena Munoz ,&nbsp;David Ortiz ,&nbsp;Elvira Perona Urizar","doi":"10.1016/j.toxicon.2025.108585","DOIUrl":"10.1016/j.toxicon.2025.108585","url":null,"abstract":"<div><div>The detection and characterization of cyanotoxins produced by benthic cyanobacteria in rivers is an understudied topic compared to cyanotoxins produced by planktonic cyanobacteria. Particularly, detection methods for cyanotoxin-producing species in Latin America and Mexico continue to focus primarily on microscopy, with relatively scarce molecular detection. Herein, we present the first study in Mexican rivers that identifies a population of the genus <em>Tychonema</em> as a producer of two variants of microcystins, MC-LR and MC-RR, through a polyphasic approach that includes the quantification of toxins by HPLC-UV. Likewise, two populations of <em>Nostoc</em> and <em>Microcoleus</em> were identified and, based on the identification of the <em>anaC</em> and <em>mcyE</em> genes via PCR, may be producers of anatoxins and microcystins, respectively; however, this production could not be confirmed in the HPLC-UV analysis. Active microcystins production was observed in eutrophic environments, while potential production was recorded in populations in oligotrophic environments. Therefore, the presence of producing strains in both types of environment cannot be ruled out. We propose that toxin production could be a mechanism of competition against other microorganisms that make up benthic mats, rather than a direct response to eutrophication. We also found that the percent coverage of toxic cyanobacterial mats is not always a reliable indicator of the amount of toxin produced. <em>Microcoleus</em> sp. showed a higher percent coverage in the river but was not toxic, while <em>Tychonema</em> sp. Produced significant amounts of MC-LR and MC-RR under the same culture conditions despite less coverage in the river. We strongly recommend the implementation of multiple techniques and methods for identifying populations of toxin-producing benthic cyanobacteria (CyanoHAMs) in Mexican rivers in order to validate the results and develop a prevention plan against their associated risks.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"267 ","pages":"Article 108585"},"PeriodicalIF":2.4,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Botulinum Toxin A (BTA) for pain and function improvement in osteoarthritis: a systematic review and meta-analysis of clinical efficacy evidence from randomized controlled trials","authors":"Beibei Lei ,&nbsp;Weisheng Zhuang ,&nbsp;Yage Wang ,&nbsp;Shenhong Ma ,&nbsp;Heling Wang ,&nbsp;Di Zhang ,&nbsp;Qiaohua Han ,&nbsp;Xu Wang ,&nbsp;Qixin Ding ,&nbsp;Yuefang Li","doi":"10.1016/j.toxicon.2025.108582","DOIUrl":"10.1016/j.toxicon.2025.108582","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the effectiveness of botulinum toxin A injections in improving pain and function in patients with osteoarthritis.</div></div><div><h3>Design</h3><div>This study systematically searched the PubMed, Web of Science, Embase, Medline, Cochrane Library, CNKI, and Wanfang databases. The primary outcome was the Visual Analogue Scale (VAS), while secondary outcomes included the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and the occurrence of adverse events.</div></div><div><h3>Results</h3><div>A total of eight randomized controlled trials (RCTs) were included. Seven studies compared VAS scores between the experimental and control groups, while three studies compared WOMAC scores. Both VAS and WOMAC scores were significantly lower in the experimental group than in the control group (P &lt; 0.00001). In addition, different sites of OA (P = 0.99), different doses of botulinum toxin A injection (P = 0.52), and different times of outcome assessment (P = 0.58) had similar effects in reducing VAS scores.</div></div><div><h3>Conclusions</h3><div>BTA injections effectively relieve overall pain perception and resting pain, but their efficacy for pain associated with specific functional activities remains uncertain. The effects of low- and high-dose regimens on reducing VAS scores are comparable, supporting the preferential use of the low-dose regimen; however, the efficacy of BTA in improving joint function remains highly uncertain.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"267 ","pages":"Article 108582"},"PeriodicalIF":2.4,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allium cepa L. as a bioindicator: A comprehensive review of genotoxicity and cytotoxicity assessment methods","authors":"Jagadisha Tavarekere Venkataravanappa ,&nbsp;Saraswathi Saraswathi ,&nbsp;Yuvaraj Shapur Gopalkrishnashetty ,&nbsp;Parvathi Soman ,&nbsp;Nayana Mitta Lakshminarayana Gupta ,&nbsp;Shreya Srivastava ,&nbsp;Shambhavi Kumari","doi":"10.1016/j.toxicon.2025.108586","DOIUrl":"10.1016/j.toxicon.2025.108586","url":null,"abstract":"<div><div><em>Allium cepa</em> L., commonly known as the bulb onion, is widely cultivated and used globally for its culinary and medicinal purposes. It plays a significant role in genotoxicity and cytotoxicity testing. Onion (<em>Allium cepa</em> L.), a perennial herb from the Amaryllidaceae family, is recognized for its high dietary fiber content. It is a biennial plant with fibrous, adventitious roots, 3–8 distichous, glaucous leaves, and a bulb made up of concentric, enlarged, fleshy leaf bases. The outer leaf bases dry out, becoming thin and varying in color to form a protective layer, while the inner bases thicken as the bulb matures. <em>Allium cepa</em> L. is widely used as a flavoring agent in the food industry and is known for its antimicrobial properties. This review discusses the <em>Allium cepa</em> L. assay (AT) as an effective and economical method for evaluating genotoxic effects through the analysis of chromosomal aberrations and DNA damage. This assay provides an alternative to animal testing and includes various methods for genotoxicity assessment, such as the comet assay and micronucleus assay, as well as techniques for cytotoxicity evaluation like the MTT assay and root growth inhibition assay. It emphasizes the sensitivity of Allium cepa L. to environmental pollutants and heavy metals that disrupt physiological processes. The article also reviews the health benefits of bioactive compounds in onions, such as sulfur compounds, saponins, and fructans, highlighting the importance of Allium cepa L. in environmental monitoring. Additionally, the review examines the impact of fungicides like mancozeb and benodanil on environmental and human health, using Allium cepa L. as a bioindicator to detect chromosomal and mitotic disturbances. This comprehensive review underscores the value of <em>Allium cepa</em> L. in environmental monitoring, its wide range of applications in toxicity assessment and research, as well as its historical and modern uses in medicine. The aim is to compile current evidence on the phytochemistry, genotoxicity, and cytotoxicity of <em>Allium cepa</em> L., emphasizing its role as a standard bioindicator in environmental and toxicological studies. Looking ahead, integrating <em>Allium cepa</em> L. assays with molecular and omics-based approaches could further enhance their utility in modern environmental monitoring and pharmaceutical toxicology.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"267 ","pages":"Article 108586"},"PeriodicalIF":2.4,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First documented cases of envenomations in mainland China by Ovophis species (mountain pitvipers): Severe coagulopathy and variable antivenom response in two patients from Yunnan Province","authors":"Zichen Qiao ,&nbsp;Yong Tang ,&nbsp;Aobo Shang ,&nbsp;You Tao ,&nbsp;Bryan G. Fry","doi":"10.1016/j.toxicon.2025.108583","DOIUrl":"10.1016/j.toxicon.2025.108583","url":null,"abstract":"<div><div>Envenomations by <em>Ovophis</em> spp. (mountain pitvipers) are clinically significant yet underreported, especially in mainland China where no confirmed cases have been documented. Here we report two cases of <em>Ovophis</em> envenoming from Yunnan Province that resulted in severe coagulopathy marked by hypofibrinogenemia and elevated D-dimer and FDP levels. In Case 1, a 51-year-old woman bitten by a confirmed <em>O. makazayazaya</em> developed moderate hypofibrinogenemia, which resolved following combined treatment with <em>Deinagkistrodon acutus</em> and <em>Gloydius brevicaudus</em> monovalent antivenoms. In Case 2, a 37-year-old woman bitten by an unidentifiable <em>Ovophis</em> species experienced complete depletion of fibrinogen and prolonged coagulopathy despite treatment with four vials of <em>G. brevicaudus</em> antivenom. These cases highlight the potent coagulotoxic effects of <em>Ovophis</em> venom. Clinical differences between two cases suggest that venom variation and differential antivenom efficacy may influence outcomes. Our findings underscore the need for further research into <em>Ovophis</em> venom composition, cross-neutralization by available antivenoms, and improved species-level identification in clinical settings.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"267 ","pages":"Article 108583"},"PeriodicalIF":2.4,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular dynamics of Lys49 PLA2-like toxins: Insights into solution and membrane-bound conformations","authors":"Rui Rachão ,&nbsp;João T.S. Coimbra ,&nbsp;Maria J. Ramos ,&nbsp;José-María Gutiérrez ,&nbsp;Bruno Lomonte ,&nbsp;Pedro A. Fernandes","doi":"10.1016/j.toxicon.2025.108581","DOIUrl":"10.1016/j.toxicon.2025.108581","url":null,"abstract":"<div><div>Snakebite envenoming is a neglected tropical disease that causes death and disability. Lysine 49 phospholipase A₂-like (Lys49 PLA₂-like) proteins are abundant toxins in many viperid venoms and play a significant role in their toxicity. They induce skeletal muscle necrosis by disrupting the plasma membrane through a mechanism independent of phospholipid hydrolysis. X-ray structures of <em>Bothrops asper</em> Lys49 PLA₂-like proteins were analysed for sequence, folding and quaternary structure, and compared with dimer geometries of Lys49 PLA₂s from other viper species in the PDB. Sequence and folding were mainly conserved, whilst quaternary structure was not. With a single exception, all quaternary structures fell into two categories: compact and extended.</div><div>The <em>B. asper</em> extended and compact Lys49 PLA₂ conformations were simulated in solution and in a membrane bilayer with molecular dynamics and scrutinised in light of mechanistic proposals and experimental data. Both conformations dissociated into monomers in solution. Membrane binding was more stable with higher fractions of negatively charged phospholipids, achieved through the inclusion of DMPA. The extended dimer desorbed in pure POPC, kept its dimeric conformation when adsorbed to POPC/DMPA (9:1), and dissociated into monomers in POPC/DMPA (1:1). Still, the protein remained adsorbed in the latter case. The compact dimer desorbed from the membrane in the pure POPC bilayer, lost its conformation in POPC/DMPA (1:1), and dissociated into monomers in a POPC/DMPA (9:1) composition. The monomers oscillated between vertical (compact-like) and horizontal (extended-like) orientations.</div><div>These scenarios show that the current hypotheses for the membrane disruption mechanism by Lys49 PLA₂-like proteins are not entirely aligned with the evidence, and alternative possibilities need to be considered. Our observations suggest that Lys49 PLA₂s could act as monomers but may also associate into higher-order oligomers during membrane interaction. This highly complex molecular scenario aligns with recent evidence indicating that the membrane promotes protein oligomerisation.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"267 ","pages":"Article 108581"},"PeriodicalIF":2.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"When venom calms the storm: Stonefish venoms suppress LPS-induced Th1 cytokine expression and secretion in human PBMCs","authors":"Silvia Luiza Saggiomo ,&nbsp;Daniel Browne ,&nbsp;Yide Wong ,&nbsp;John J. Miles ,&nbsp;Denise Doolan ,&nbsp;Norelle L. Daly ,&nbsp;David Thomas Wilson","doi":"10.1016/j.toxicon.2025.108579","DOIUrl":"10.1016/j.toxicon.2025.108579","url":null,"abstract":"<div><div>Venoms are known to modulate immunological processes. In this study, we investigated the immunomodulatory properties of venoms from two stonefish species, <em>Synanceia verrucosa</em> (SvV) and <em>Synanceia horrida</em> (ShV), using immunological assays including reverse-transcription quantitative polymerase chain reaction (RT-qPCR), cytometric bead array (CBA), and enzyme-linked immunosorbent assay (ELISA). Both venoms exhibited significant immunosuppressive activity, particularly in lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMCs), with less pronounced effects on phorbol 12-myristate 13-acetate with ionomycin (P/I)-stimulated cells. The venoms primarily suppressed Th1-associated cytokines (TNF, IFN-γ, IL-6, and IL-12), as well as IL-10 (Th2) and MCP-1, indicating a stronger inhibition of the Th1 subset. SvV demonstrated greater activity compared to ShV, suppressing cytokines on which ShV had no effect, and having activity at concentrations as low as 1.25 μg/mL. Stability studies showed that both frozen and lyophilized venoms retained immunosuppressive activity comparable to fresh venom, while reversed-phase high-performance liquid chromatography (RP-HPLC) abolished this activity entirely. Size-exclusion chromatography (SEC) revealed the immunosuppressive activity was strongest in the early and late fractions of each venom. Our results highlight the selective immunosuppressive effects of <em>S. verrucosa</em> and <em>S. horrida</em> venoms on human PBMCs, particularly via modulation of Th1 cytokines in response to LPS. The stability and bioactivity of specific venom fractions underscore their potential as sources for novel immunotherapeutic agents.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"267 ","pages":"Article 108579"},"PeriodicalIF":2.4,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145046571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The ameliorative effects of Honokiol on intracerebroventricular Kainic acid-induced spinal cord neurotoxicity","authors":"Tansu Kuşat ,&nbsp;Feyza Başak ,&nbsp;Emine Ümran Örsçeli̇k ,&nbsp;Oğuzhan Koca ,&nbsp;Güngör Çağdaş Di̇nçel","doi":"10.1016/j.toxicon.2025.108568","DOIUrl":"10.1016/j.toxicon.2025.108568","url":null,"abstract":"<div><div>Kainic acid (Ka) is a neuroexcitatory agent commonly utilized in the modeling of excitotoxicity. The study aims to investigate both the neurotoxic effects of intracerebroventricular (icv) Ka injections in rats on the cervical spinal cord and the therapeutic role of honokiol. Fifty male Wistar Albino rats (n = 10) are divided into five groups. The control group of rats received normal saline by intraperitoneal (ip) injection for a duration of 7 days. The sham group of rats was administered a single dose of icv normal saline on the first day. Rats in the Ka group received a single icv dosage of Ka (0.5 μg/μl). Honokiol (Hnl) group rats Hnl for 7 days (ip-5 mg/kg), while Ka + Hnl group rats were administered Ka (single dose) and Hnl (7 days). Exhibited substantial histopathological alterations and an increase in glial fibrillary acidic protein (GFAP) positive (+) cells in the rats in the Ka group. In the Ka + Hnl group of rats, an improvement in histological structure and a reduction in GFAP (+) cells compared to the Ka group. The central canal lumen diameters were significantly expanded in the Ka group rats. It was observed that malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) levels increased and glutathione (GSH) levels decreased in the spinal cord of rats in the Ka group. Hnl treatment caused a significant improvement in MDA and GSH levels and a decrease in TNF-α levels in rats with the excitotoxicity model. In conclusion, the findings showed that Hnl treatment attenuated Ka-induced neurotoxicity by reducing oxidative tissue damage, inflammatory response, and GFAP expression.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"267 ","pages":"Article 108568"},"PeriodicalIF":2.4,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145046529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melanoxetin modulates oxidative, inflammatory and apoptotic pathways to confer cardio-protection against flumethrin-induced sub-chronic toxicity","authors":"Hesham M. Hassan ,&nbsp;Aqsa Bibi ,&nbsp;Giorgio Antoniolli ,&nbsp;Mahmoud El Safadi ,&nbsp;Khalid J. Alzahrani ,&nbsp;Fuad M. Alzahrani ,&nbsp;Abrar Aljohani ,&nbsp;Adnan Ali","doi":"10.1016/j.toxicon.2025.108580","DOIUrl":"10.1016/j.toxicon.2025.108580","url":null,"abstract":"<div><div>Flumethrin (FLU) is a broad-spectrum pyrethroid that has been evidenced to cause various cardiac impairments. Melanoxetin (MEL) is a natural polyphenolic compound with diverse biological abilities. This research was executed to analyze the recuperative potential of MEL against FLU provoked sub-chronic cardiotoxicity in rats. Thirty-six Sprague Dawley rats were categorized into the control, FLU (5 mg/kg) intoxicated, FLU (5 mg/kg) + MEL (10 mg/kg) therapeutic and MEL (10 mg/kg) alone administered group. Our findings showed that FLU intoxication increased the gene expressions of Toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), NLRP3, high mobility group box 1 (HMGB1), tumor necrosis factor-α (TNF-α), receptor for advanced glycation end-products (RAGE) interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2) &amp; interleukin-6 (IL-6) while increasing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Moreover, the enzymatic activities of glutathione peroxidase (GPx), glutathione reductase (GSR), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), heme-oxygenase-1 (HO-1) and glutathione (GSH) were lowered whereas the levels of Troponin I, pro B-type natriuretic peptide (ProBNP), creatine kinase-myocardial band (CK-MB) C-reactive protein, Lactate dehydrogenase (LDH), troponin-T, Brain natriuretic peptide (BNP) and Creatine phosphokinase (CPK) were increased following the FLU intoxication. Furthermore, FLU exposure promoted the levels of Bax, Caspase-9, and Caspase-3 while lowering the levels of Bcl-2. FLU administration abruptly damages the morphology of heart tissues. Nonetheless, MEL therapy excellently ameliorated cardiac toxicity by virtue of its anti-inflammatory, antioxidative and anti-apoptotic potential. Collectively, MEL may serve as a cardioprotective agent in counteracting FLU provoking sub-chronic cardiotoxicity.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"267 ","pages":"Article 108580"},"PeriodicalIF":2.4,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145046547","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}