Toxicon最新文献

{"title":"Comment on \"Interaction of cholinesterase inhibitors with snake venom acetylcholinesterase from snake species of Southern Africa\" (Petzer et al., 2025).","authors":"Parth Aphale, Shashank Dokania, Himanshu Shekhar","doi":"10.1016/j.toxicon.2025.108558","DOIUrl":"10.1016/j.toxicon.2025.108558","url":null,"abstract":"","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":" ","pages":"108558"},"PeriodicalIF":2.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993663","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":"Corrigendum to ‘Kraits of Indian subcontinent: Natural history, risks, venom variation, lethality and treatment strategies – A comprehensive review’ [Toxicon 262 (2025) 108406]","authors":"Amit Talukdar , Surajit Giri , Robin Doley","doi":"10.1016/j.toxicon.2025.108557","DOIUrl":"10.1016/j.toxicon.2025.108557","url":null,"abstract":"","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"266 ","pages":"Article 108557"},"PeriodicalIF":2.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144921530","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":"Aflatoxin B1-Induced male reproductive Toxicity: Bioactivation, mechanisms, molecular pathways, and Mitigation by phytochemicals in humans and animals","authors":"Zemin Zhu ,&nbsp;Muhammad Shahab ,&nbsp;Shahab Uddin ,&nbsp;Imdadullah ,&nbsp;Muhammad Ishfaq","doi":"10.1016/j.toxicon.2025.108554","DOIUrl":"10.1016/j.toxicon.2025.108554","url":null,"abstract":"<div><div>Aflatoxins (AFTs) represent a major subclass of mycotoxins that are widely recognized as critical contaminants in both food systems and environmental matrices (soil, water, air dust). Among them, aflatoxin B1 (AFB1) is identified as the most toxic and biologically active compound, exhibiting a broad spectrum of deleterious effects, including nephrotoxicity, immunotoxicity, neurotoxicity, hepatotoxicity and genotoxicity. Increasing evidence has highlighted the role of AFB1 in impairing reproductive health, with a particular emphasis on AFB1-induced infertility in both humans and animals. The compound adversely affects the architecture and physiological functions of reproductive organs, leading to disrupted gametogenesis in males and consequent reductions in fertility rates. These testicular toxicities pose serious threats to public health, food security, and animal productivity. The molecular mechanisms implicated in AFB1-mediated reproductive damage include apoptosis, inflammation, autophagy, cell cycle dysregulation, and oxidative stress. Recently, naturally derived phytochemicals have emerged as promising countermeasures due to their low toxicity at appropriate doses and natural structural motifs. These bioactive compounds exert antioxidant, anti-inflammatory, and anti-apoptotic effects, thereby mitigating AFB1-induced germ cell toxicity. Additionally, certain phytochemicals modulate the biotransformation and detoxification of AFB1 in vivo, reducing its genotoxic potential and facilitating its excretion. This review provides a comprehensive analysis of AFB1-induced testicular toxicity in male mammals, with a focus on the underlying molecular pathways and protective roles of various plant-based agents. It further delineates the mechanistic basis for the anti-AFB1 activity of these phytochemicals, drawing attention to their shared properties and species-specific responses. Here, we identify existing gaps in current research and propose future directions to optimize phytochemical interventions. Overall, this review underscores the therapeutic potential of phytochemicals in alleviating AFB1-associated reproductive dysfunction through targeted modulation of critical signaling pathways.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"267 ","pages":"Article 108554"},"PeriodicalIF":2.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933823","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":"Identification of a novel insecticidal chlorotoxin-like peptide from the venom of the Compsobuthus egyptiensis scorpion","authors":"Alhussin Mohamed Abdelhakeem Megaly ,&nbsp;Ryusuke Nakamichi ,&nbsp;Masashi Wakayu ,&nbsp;Yoshiaki Nakagawa ,&nbsp;Mohammed Abdel-Wahab ,&nbsp;Masahiro Miyashita","doi":"10.1016/j.toxicon.2025.108556","DOIUrl":"10.1016/j.toxicon.2025.108556","url":null,"abstract":"<div><div>Scorpion venom contains various bioactive peptides, but there are many scorpion species whose venom has not been studied. The genus <em>Compsobuthus</em>, belonging to the family Buthidae, is relatively diverse, but there have been no reports on their venom components. In the present study, we characterized venom components of the <em>Compsobuthus egyptiensis</em> scorpion inhabiting the northern Egyptian desert. Mass spectrometry analysis of the venom revealed that the components with molecular masses from 3000 to 4000 Da were relatively abundant among 198 components detected. We then isolated a novel insecticidal peptide, Ce-1, from one of the HPLC fractions showing insecticidal activity. The structure of Ce-1 was determined using a combination of Edman degradation and <em>de novo</em> MS/MS sequencing analyses. This revealed that Ce-1 consists of 36 amino acid residues with four disulfide bonds. The deduced structure was confirmed by comparison with the synthetic peptide. Ce-1 shares high sequence homology to chlorotoxin-like peptides, which consist of an α-helix and an antiparallel triple-stranded β-sheet cross-linked by four disulfide bonds. Future research on Ce-1 will contribute to elucidating the mechanism of action of insecticidal chlorotoxin-like peptides.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"267 ","pages":"Article 108556"},"PeriodicalIF":2.4,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970589","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":"Melittin-induced modulation of mitochondrial physiology: Beyond the antitumoral actions","authors":"Marcos Roberto de Oliveira","doi":"10.1016/j.toxicon.2025.108555","DOIUrl":"10.1016/j.toxicon.2025.108555","url":null,"abstract":"<div><div>Melittin (MEL), a cationic amphipathic peptide derived from bee venom, exhibits dual roles in mitochondrial physiology, with both cytoprotective and cytotoxic outcomes. This review synthesizes current findings on MEL-induced modulation of mitochondrial pathways in normal and cancer cells. Beyond its well-documented roles in apoptosis regulation, MEL influences mitochondrial function by altering membrane potential, regulating respiratory chain activity, and impacting ATP production. These effects are context-dependent and vary across normal and tumor cell models. MEL can attenuate mitochondrial dysfunction by preserving mitochondrial membrane integrity and reducing reactive oxygen species, while in cancer cells, it often promotes mitochondrial depolarization, cytochrome <em>c</em> release, and caspase activation, culminating in intrinsic apoptotic signaling. Importantly, MEL modulates the expression of key proteins such as BAX, BCL-2, and APAF-1, and interacts with signaling cascades including PI3K/Akt, NF-κB, MAPKs, and Nrf2/HO-1. Recent studies have demonstrated that MEL also regulates mitochondrial quality control mechanisms, including the stimulation of mitophagy through PINK1/Parkin and AMPK-related pathways. Moreover, MEL interacts directly with mitochondrial membranes and affects enzymes critical for energy metabolism, such as F1-ATPase, contributing to altered bioenergetic output. These actions suggest that MEL's mitochondrial effects extend beyond cell death regulation, encompassing broader control over metabolic activity, oxidative stress, and organelle maintenance. Future investigations should integrate redox biology, bioenergetics, and mitochondrial signaling to optimize MEL's therapeutic applications. Altogether, MEL represents a unique modulator of mitochondrial health, whose dual actions necessitate rigorous contextual evaluation for clinical translation.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"266 ","pages":"Article 108555"},"PeriodicalIF":2.4,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144931959","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":"Deoxynivalenol regulates intestinal and stem cell regeneration via the Hippo pathway and clinical intervention strategies","authors":"Peng Liao","doi":"10.1016/j.toxicon.2025.108553","DOIUrl":"10.1016/j.toxicon.2025.108553","url":null,"abstract":"<div><div>This review article examines the molecular pathways through which the environmental contaminant deoxynivalenol (DON) influences the regeneration and renewal of both intestinal tissues and intestinal stem cells via the Hippo Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) signaling cascade, while also exploring possible clinical intervention approaches. To begin, the review outlines the prevalent issue of DON contamination and its adverse effects on gastrointestinal health, underscoring the necessity for a comprehensive understanding of its implications. Subsequently, the discussion focuses on the significance of the Hippo YAP/TAZ pathway in preserving the homeostasis of intestinal stem cells and clarifies the mechanisms by which DON perturbs this essential process. In conclusion, the article consolidates potential therapeutic targets and clinical strategies designed to mitigate the intestinal damage caused by DON, thereby providing fresh perspectives on treatment options for gut injuries.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"266 ","pages":"Article 108553"},"PeriodicalIF":2.4,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144931958","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":"Azithromycin and Gallic acid alleviate neurobehavioral deficits in rats resulting from chronic Aflatoxin B1 exposure","authors":"Solomon Owumi ,&nbsp;Joseph Chimezie ,&nbsp;Idris O. Bello ,&nbsp;Moses T. Otunla ,&nbsp;Uche Arunsi ,&nbsp;Ayomide P. Akomolafe ,&nbsp;Jesutosin O. Babalola ,&nbsp;Chioma E. Irozuru ,&nbsp;Olatunde O. Owoeye","doi":"10.1016/j.toxicon.2025.108552","DOIUrl":"10.1016/j.toxicon.2025.108552","url":null,"abstract":"<div><div>Aflatoxin B₁ (AFB₁) is a mycotoxin known for its liver toxicity and cancer risk, as well as neurotoxic effects causing motor and cognitive issues in humans and animals. Ongoing research into protecting against AFB₁ damage has recently focused on antioxidant and anti-inflammatory agents. Gallic acid (GA), a low molecular weight triphenolic acid, demonstrates notable anti-oxidative and anti-inflammatory activities. Furthermore, Azithromycin (AZT), an antibiotic, has shown promise in mitigating inflammatory stress in experimental models. GA and AZT may help protect against AFB₁-induced neurobehavioral deficits in rats. This experiment involved thirty-five rats randomly assigned to seven cohorts (n = 5), over a 28-day treatment period. The study consisted of a control group given corn oil, a group exposed only to AFB₁, and groups that received GA, AZT, or combinations of these substances with AFB₁. The neurobehavioral status of the experimental rats was assessed using the Open Field Test (OFT) and Novel Object Recognition Test (NORT) on days 26 and 27, respectively. On day 28 following treatment, the Elevated Plus Maze (EPM), Y-maze, and Forced Swim Test (FST) were conducted. After behavioural evaluation, the rats were euthanised. The hippocampus and prefrontal cortex were dissected for biochemical analysis. Antioxidant enzyme activities (SOD, CAT, GPx, GST), GSH and TSH levels, acetylcholinesterase, and markers of oxidative stress (RONS, LPO) and inflammation (NO, MPO) were measured. AFB₁ exposure raised oxidative stress markers, MPO, and AChE activity, while lowering antioxidant enzymes in the hippocampus and prefrontal cortex, indicating notable neurotoxicity and signalling disruptions. Combined GA and AZT treatment improved antioxidant defence, reduced inflammation, and restored AChE activity. Neurobehavioral tests indicated better motor and cognitive function after AFB₁ exposure. These results suggest that GA and AZT together offer strong protection against AFB1-induced neurotoxicity via their antioxidant and anti-inflammatory effects.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"266 ","pages":"Article 108552"},"PeriodicalIF":2.4,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144917589","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":"Amelioration of diethylnitrosamine-induced acute brain injury by α-eudesmol and β-eudesmol","authors":"Gulsah Yildiz Deniz ,&nbsp;Fatime Geyikoglu","doi":"10.1016/j.toxicon.2025.108550","DOIUrl":"10.1016/j.toxicon.2025.108550","url":null,"abstract":"<div><div>Diethylnitrosamine (DEN) is a widely distributed environmental pollutant known for its toxicity and carcinogenicity in various animal species. The aim of the study was to investigate the neuroprotective effects of α-eudesmol and β-eudesmol against DEN-induced brain damage in rats. Sprague-Dawley rats received a single intraperitoneal dose of DEN (200 mg/kg), followed by intravenous administration of α-eudesmol or β-eudesmol (1 mg/kg) three times weekly for 21 days. Brain tissues were collected for histological, biochemical, and immunohistochemical analyses, including markers of brain injury (c-fos) and apoptosis (caspase 3). DEN exposure significantly decreased antioxidant enzyme activities (catalase, glutathione peroxidase, and superoxide dismutase) and increased oxidative stress marker malondialdehyde. It also triggered platelet activation, inflammatory cytokine production, and pathological changes in brain tissue, accompanied by upregulated c-fos and caspase 3 expression. Treatment with α-eudesmol and β-eudesmol effectively mitigated these alterations by modulating the NF-κB/COX-2/TNF-α/IL-6 signaling pathways and restoring dopamine levels to near control values. These findings highlight the potential of α-eudesmol and β-eudesmol as therapeutic agents against DEN-induced neurotoxicity.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"266 ","pages":"Article 108550"},"PeriodicalIF":2.4,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925713","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":"Expanding the repertoire of conopeptides from the venom of the vermivorous snail Conus regius","authors":"Helena B. Fiorotti ,&nbsp;Suely G. Figueiredo ,&nbsp;Emídio Beraldo-Neto ,&nbsp;Fabiana V. Campos ,&nbsp;Daniel C. Pimenta","doi":"10.1016/j.toxicon.2025.108551","DOIUrl":"10.1016/j.toxicon.2025.108551","url":null,"abstract":"<div><div>This study presents a comprehensive proteomic characterization of <em>Conus regius</em> venom. Venom samples were fractionated using reversed-phase chromatography and analyzed by Q-TOF mass spectrometry. Spectral data were processed with Peaks Studio V7.0 and searched against a <em>Conus</em> protein database. A total of 520 peptide and protein sequences were identified, with most corresponding to conopeptides. Among these, eight presented similarities to disulfide-poor conopeptides of the Conantokin, ConoGay, and ConoCAP classes, as well as two sequences not classified in the literature. Additionally, 284 peptides showed similarity to conotoxins from 13 gene superfamilies (M, A, T, P, S, I1, Conodipine, O1, Insulin, G2, O2, Q, and H), while 102 sequences were linked to undetermined superfamilies. Of the identified sequences, 21 had been previously described in <em>C. regius</em> venom, while many others shared similarities with conotoxins from other <em>Conus</em> species. Most conotoxins identified were associated with the M and A superfamilies, suggesting their predominance in the venom. This study expands the known repertoire of <em>C. regius</em> venom components and provides valuable insights into its molecular diversity, supporting future research into its biotechnological potential.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"266 ","pages":"Article 108551"},"PeriodicalIF":2.4,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908222","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":"In silico multiscale computational modelling of botulinum toxin a diffusion for glabellar wrinkle treatment: Optimizing injection volumes across formulations","authors":"Eqram Rahman ,&nbsp;Jean D.A. Carruthers ,&nbsp;Parinitha Rao ,&nbsp;Munim Ahmed ,&nbsp;Greg J. Goodman ,&nbsp;William Richard Webb","doi":"10.1016/j.toxicon.2025.108548","DOIUrl":"10.1016/j.toxicon.2025.108548","url":null,"abstract":"<div><div>While botulinum neurotoxin A (BoNT/A) is a cornerstone in glabellar wrinkle treatment, inconsistencies in clinical outcomes often stem from formulation-dependent diffusion behaviour. Currently volumes recommendation per site lacks mechanistic justification, especially in anatomically confined regions like the glabella, where millimetric diffusion differences can produce significant adverse effects. A high-fidelity, multiscale in silico platform was developed, integrating quantum mechanical (TD-DFT) modelling of SV2-binding (ΔG_bind range: −9.2 to −11.7 kcal/mol), molecular dynamics-derived hydrodynamic radius (R_H: 9.4–11.2 nm), anisotropic finite element modelling of poroelastic muscle tissue, and agent-based receptor and immune kinetics. Simulations encompassed five formulations— AbobotulinumtoxinA (ABO), DaxibotulinumtoxinA (DAXI), IncobotulinumtoxinA (INCO), OnabotulinumtoxinA (ONA), and PrabotulinumtoxinA (PRABO)—across injection volumes from 0.025 to 0.1 mL, at fixed toxin unit dosing, within anatomically realistic glabellar meshes (n = 10,000 synthetic patient variants). Diffusion profiles varied significantly by formulation. ABO showed the largest Reff (1.64 ± 0.14 cm) and E_off, while PRABO and ONA remained spatially constrained (Reff = 0.96 ± 0.07 cm and 1.13 ± 0.08 cm, respectively). Increasing injection volume from 0.025 to 0.1 mL caused a 2.2-fold rise in E_off and a 36–49 % increase in off-target V_IC50 across formulations. Optimal containment was formulation-specific: PRABO and ONA achieved ≥95 % V_IC90 coverage with &lt;10 % V_IC50 spillover at 0.025–0.035 mL; INCO and DAXI required 0.035–0.05 mL; ABO balanced broader coverage with acceptable diffusion at 0.04–0.045 mL. Agent-based models revealed 78 % receptor saturation at 0.025 mL versus 56 % at 0.1 mL, with immune clearance rates up to 42 % higher at high volumes due to increased perivascular redistribution. Volume emerged as the dominant spread driver (Sobol S₁ = 0.48), followed by hydrodynamic radius (S₁ = 0.35) and macrophage density (S₁ = 0.28); interaction terms were negligible (S_T − S₁ &lt; 0.05). This study provides the first in-silico quantitative, multiscale evidence that reducing BoNT/A reconstitution volume to ≤0.045 mL/site significantly enhances target localization while minimizing off-target effects. Contrary to prevailing clinical heuristics, dilution amplifies mechanical spread and immune clearance risk.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"266 ","pages":"Article 108548"},"PeriodicalIF":2.4,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908083","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}