Toxicology Mechanisms and Methods最新文献

{"title":"Dual route of polystyrene micro- and nanoplastics exposure increases <i>in vivo</i> leukocyte-endothelium interactions and aligns with organ injury.","authors":"Mustafa Sevim, Alperen Akbaba, Dila Şener Akçora, Dilan Özaydın, Doğa Akkuş, Selin Başer, Ebru Yıldız, Enes Erzurumluoğlu, Emirhan Sarıçiçek","doi":"10.1080/15376516.2026.2741367","DOIUrl":"10.1080/15376516.2026.2741367","url":null,"abstract":"<p><p>Micro- and nanoplastics are pervasive environmental contaminants, yet direct in vivo evidence linking mixed-route exposure to leukocyte-endothelium interactions remains limited. Here, we investigated the effects of 28-day dual-route polystyrene exposure (oral microplastics and inhalational nanoplastics) in a sex-stratified murine model. Using intravital microscopy of mesenteric post-capillary venules, we quantified leukocyte rolling, stationary events and firm adhesion under physiological flow. Exposure increased leukocyte-endothelium interactions across the trafficking cascade compared with controls. Sex-stratified values are reported descriptively and are exploratory. Peripheral blood analysis showed higher total leukocyte counts and lymphocyte proportions in exposed animals. Fluorescence screening, restricted to the microplastic emission channel, revealed particle-associated signals on gastrointestinal tract, lung and brain surfaces. These organs exhibited biochemical and histopathological alterations, including increased lung malondialdehyde, reduced brain glutathione and structural injury in ileum, lung and brain tissues. Behavioral testing indicated impaired recognition and spatial working-memory-related performance, while anxiety-like behavior remained unaltered. These findings show that dual-route polystyrene exposure increases leukocyte-endothelium interactions in vivo, accompanied by organ-specific biochemical, structural and behavioral alterations. Because oral microplastics and inhaled nanoplastics were administered together and no single-route or single-size control group was included, the design does not allow the contribution of one route or one size class to be separated from the other. Endothelial activation, leukocyte activation, adhesion molecules and inflammatory mediators were not measured, so the increased interactions are reported here as an association and not as a demonstrated mechanism. This work supports leukocyte-endothelium interactions as a plausible physiological component contributing to the systemic response to micro- and nanoplastic exposure, highlighting the need for further studies of leukocyte and endothelial activation, inflammatory signaling and barrier dysfunction.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-16"},"PeriodicalIF":2.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138381","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":"Microplastics and nanoplastics in humans: a critical ADME appraisal and the case for quantitative risk assessment.","authors":"Johnson Olamide Aderinmola","doi":"10.1080/15376516.2026.2739342","DOIUrl":"10.1080/15376516.2026.2739342","url":null,"abstract":"<p><p>Microplastics (MPs, 1 µm-5 mm) and nanoplastics (NPs, <1 µm) have now been detected in every environmental compartment and in human tissues, including blood, lung, placenta, liver, and brain. Detection alone isn't enough for health risk assessment. The key question is not just presence, but what happens to particles inside the body, which requires rigorous toxicokinetic data. This review critically evaluates the evidence on the absorption, distribution, metabolism, and excretion (ADME) of MPs and NPs in humans, applying an explicit evidence-level framework (Section 1.1) to weigh the quality of the underlying studies rather than simply summarising them. Gastrointestinal absorption is mechanistically plausible but quantitatively undefined: no human mass-balance study has yet measured an absorption fraction. Tissue detection confirms systemic distribution, but no study has established concentration gradients, kinetic profiles, or true bioaccumulation as distinct from transient presence. Polymer backbones resist enzymatic degradation, so classical metabolic biotransformation does not apply; surface oxidation and additive leaching are the primary biochemical interactions instead. Excretion pathways are constrained by particle size and remain poorly characterised, and systemic clearance kinetics are entirely unknown. These gaps are caused by an analytical paradox: current spectroscopic techniques can't reliably detect particles below 1-20 µm, excluding the nanoscale particles most likely to cross biological barriers. No validated human physiologically based toxicokinetic (PBTK) model exists. Turning environmental detection data into credible risk assessment requires standardised biomonitoring, isotopically labelled tracer studies in humans, and a validated PBTK model. Until then, neither reassurance nor alarm about human health risk is scientifically justified.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-24"},"PeriodicalIF":2.7,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040713","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":"Artificial Intelligence and machine learning in toxicogenomics for drug safety assessment: a critical review.","authors":"Baseerat Fatima, Minal Zaka, Maham Ashraf, Nyla Ajaz","doi":"10.1080/15376516.2026.2741364","DOIUrl":"https://doi.org/10.1080/15376516.2026.2741364","url":null,"abstract":"<p><strong>Introduction: </strong>Predicting drug-induced toxicity remains one of the principal bottlenecks in drug development: <i>in vivo</i> and <i>in vitro</i> assays are resource-intensive, and their concordance with human-specific toxicity is often limited. Toxicogenomics addresses this gap by linking chemical exposure to gene-expression and pathway-level changes, offering mechanistic insight that conventional endpoints cannot provide.</p><p><strong>Objectives: </strong>Artificial intelligence (AI) and machine learning (ML) increasingly analyze these high-dimensional datasets drawn from resources such as Tox21, ToxCast, TG-GATEs, LINCS, Drug Matrix, CTD and DrugBank to model complex, non-linear relationships between molecular signatures and organ-specific toxicities such as hepatotoxicity, nephrotoxicity and cardiotoxicity. Although previous surveys have catalogued AI/ML applications in predictive toxicology, few have critically examined how dataset composition, validation strategy, interpretability and regulatory requirements jointly determine whether these predictions can be trusted. This review addresses that gap.</p><p><strong>Results: </strong>Its central finding is that AI/ML has substantially expanded the analytical capacity of toxicogenomics, but reported predictive performance commonly AUC values spanning roughly 0.70 to above 0.90 for the same clinical endpoint does not by itself establish biological validity, external generalizability, reproducibility, or regulatory acceptance. This variability is caused by chemical biases, species biases in public datasets, as well as low sample size and imbalanced samples, nearuniversal use of internal crossvalidation, while independent external testing is preferred, and batch effects that do not always get corrected. Explainable AI methods (SHAP, LIME, attention mechanisms) may be employed to find potential biomarkers and more generally to improve the mechanistical transparency (but are not regulatory-grade mechanistical evidence, as they are not proven by independent experiments and are sometimes sensitive to minor changes in the input).</p><p><strong>Conclusion: </strong>We feel that methodological discipline, including the use of standardized benchmark datasets, the external validation of the datasets as standard practice, instead of optional, balanced reporting of performance, the characterization of applicability domains, and proactive experimental confirmation of computationally-derived biomarkers, are important areas requiring future improvements. Without improving data quality, benchmarking, and reporting standards, the use of multi-omics approaches, further validated explainable architectures, and careful, careful reporting of provenance with generative AI may provide plausible paths for increasing the translational and regulatory potential of AI-driven toxicogenomics in the future.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-16"},"PeriodicalIF":2.7,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115298","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":"Hepatotoxic and nephrotoxic effects of etoxazole in rats: dose-response relationships, oxidative stress mechanisms, and provisional NOAEL/LOAEL estimates.","authors":"Bedia Bati, Neşe Eray Vuran, Ahmet Dündar, Güldidar Basmacı, İsmail Çelik","doi":"10.1080/15376516.2026.2692587","DOIUrl":"10.1080/15376516.2026.2692587","url":null,"abstract":"<p><p>Etoxazole (ETX) is a widely used organofluorine acaricide/insecticide applied to many food crops, and its residues have been detected in food matrices at levels of concern for human dietary exposure. However, its hepatotoxic and nephrotoxic potential following subchronic oral exposure remains insufficiently characterized. This study investigated the dose-dependent effects of repeated oral ETX administration on serum biochemical parameters, hepatic and renal antioxidant enzyme activities, lipid peroxidation, and histopathological features in Wistar albino rats. Six groups of seven female rats each received normal control (NC) or ETX at 25, 100, 250, 500, or 750 mg/kg/day by gavage for 28 consecutive days. At the end of the exposure period, serum parameters (AST, ALT, ALP, GGT, creatinine, uric acid, glucose, total cholesterol, triglycerides, HDL, LDL), catalase (CAT), glutathione S-transferase (GST), reduced glutathione (GSH), and malondialdehyde (MDA) levels in liver and kidney tissues, and histopathological changes were evaluated. ETX caused significant, dose-dependent increases in AST and ALT from ETX100, in ALP and GGT from ETX500, and in creatinine and uric acid at higher doses, indicating progressive hepatic and renal injury. Hepatic and renal CAT, GST, and GSH activities significantly decreased, whereas MDA levels significantly increased in the higher-dose groups, demonstrating oxidative stress-mediated disruption of antioxidant defenses. Histopathological evaluation revealed dose-dependent liver injury and significant tubular damage in kidneys. The tentative NOAEL and LOAEL were estimated at 25 and 100 mg/kg/day, respectively. These findings demonstrate that ETX induces dose-dependent hepatorenal toxicity in rats through an oxidative stress-mediated mechanism and provide relevant data for dietary risk assessment.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1468-1480"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148296434","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":"Iodinated contrast media nephrotoxicity: evolving mechanisms from osmotic stress to molecular pathways.","authors":"Huixian Zhang, Zongli Diao, Wenhu Liu","doi":"10.1080/15376516.2026.2683805","DOIUrl":"10.1080/15376516.2026.2683805","url":null,"abstract":"<p><p>Iodinated contrast media represent exogenous chemical stressors that can induce renal tubular toxicity, particularly in individuals with preexisting renal dysfunction. Contrast-induced acute kidney injury (CI-AKI) is increasingly recognized as a form of chemically mediated tubular epithelial cell injury rather than a purely hemodynamic phenomenon. Despite the clinical transition from high-osmolar to low- and iso-osmolar contrast media, nephrotoxicity persists, underscoring the limitations of osmolality-centered paradigms and the need for a mechanistic toxicology framework. This narrative review integrates experimental, translational, and clinical evidence to illuminate the toxicological mechanisms underlying contrast media induced renal tubular epithelial cell (RTEC) injury. By synthesizing classical physicochemical determinants-including osmolality, ionicity, and viscosity-with emerging molecular insights, we identify viscosity-dependent tubular flow perturbation, prolonged intrarenal retention, mitochondrial dysfunction, and oxidative stress as the key upstream toxic events. These converge on a complex network of regulated cell death pathways, including apoptosis, ferroptosis, and pyroptosis, with RTEC as the primary toxicological target. This perspective supports improved understanding of CI-AKI pathogenesis and mechanism-based prevention strategies.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1288-1304"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148151419","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":"Dissociating hepatocellular necrosis from hepatic encephalopathy: a murine acetaminophen model to identify second-hit drivers of acute liver failure.","authors":"Jenna Strickland, Yining Jin, Cheryl E Rockwell, Anne M Dorrance, Bryan L Copple","doi":"10.1080/15376516.2026.2686724","DOIUrl":"10.1080/15376516.2026.2686724","url":null,"abstract":"<p><p>Acetaminophen (i.e. paracetamol; APAP) overdose is the most common cause of acute liver injury in the United States, yet outcomes range from recovery to acute liver failure (ALF), defined by coagulopathy and hepatic encephalopathy (HE). Clinical decision-making is difficult because routine indices of hepatocellular injury (e.g. ALT/AST) do not reliably predict which patients will recover versus progress to ALF. This underscores the need to define mechanisms that drive progression to ALF and to discover biomarkers that better predict clinical trajectory. A major barrier is the lack of an experimentally tractable model in which severe hepatocellular injury is comparable, but neurological outcome diverges-a defining feature of human APAP toxicity. To address this, we established APAP dosing conditions in mice that produce similar peak liver injury yet distinct clinical courses. Mice treated with 300 mg/kg or 500 mg/kg APAP exhibited comparable increases in ALT and hepatic necrosis. In contrast, only 500 mg/kg APAP caused robust neurological dysfunction consistent with HE, including impaired reflex integrity and motor coordination, accompanied by cerebral edema and reduced cerebral blood flow. Hyperammonemia is widely implicated in HE, but ammonia levels do not always track with HE severity in patients, suggesting additional cooperating factors. Consistent with this clinical discordance, blood ammonia increased to a similar extent in both dosing groups despite clear divergence in neurological impairment. Together, these findings establish a patient-relevant platform that dissociates hepatocellular necrosis (and hyperammonemia) from HE, enabling identification of mediators that drive neurovascular dysfunction and the transition from severe liver injury to ALF.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1400-1407"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148273145","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 mechanism of the PI3K/akt/NF-κB pathway in wasp venom-induced acute liver injury in rats: a preliminary study.","authors":"Fangfang Deng, Ronghui Chen, Wenxin Luo, Jie Liu, Guangli Yang, Lihong Ma, Tianxi Zhang","doi":"10.1080/15376516.2026.2679608","DOIUrl":"10.1080/15376516.2026.2679608","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to preliminarily investigate the regulatory role of the PI3K/Akt/NF-κB signaling pathway in the process of wasp venom-induced acute liver injury.</p><p><strong>Methods: </strong>Rats were randomly divided into four groups using a random number table: Control group, PDTC group, ALI group, and ALI+PDTC group.</p><p><strong>Results: </strong>Significant changes were observed in the ALI group in the following aspects: (1) Behavioral Changes: Rats exhibited reduced activity and agitation 6 h after toxin exposure, with gradual relief observed after 24 h. (2) Biochemical Tests: The ALT and AST levels were significantly elevated at all time points (<i>p</i> < 0.05). (3) Pathological Changes: Liver cord structure disorganization, extensive necrosis, and neutrophil infiltration were observed, indicating time-dependent liver injury. (4) Inflammatory Cytokines: Levels of IL-6, TNF-α, and IFN-γ were significantly increased (<i>p</i> < 0.05), while IL-10 levels were decreased (<i>p</i> < 0.05). (5) Protein Expression: The expression of PI3K, Akt, and NF-κB p65 proteins was significantly elevated (<i>p</i> < 0.05). No significant differences were found between the Control and PDTC groups (<i>p</i> > 0.05), while the ALI+PDTC group showed notable relief.</p><p><strong>Conclusion: </strong>This study successfully established a rat model of acute liver injury induced by wasp venom and found that the aberrant activation of the PI3K/Akt/NF-κB signaling pathway may contribute to liver injury progression by promoting inflammation. The NF-κB inhibitor PDTC significantly alleviated liver injury, an effect possibly associated with suppression of this pathway, providing a new theoretical basis for targeted treatment of secondary liver injury caused by clinical wasp stings.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1379-1387"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148151454","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":"Predictive modeling of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) in metal workers: a comparative study of machine learning algorithms in toxicology.","authors":"Ali Sani, Ibrahim Lawal Abdullahi","doi":"10.1080/15376516.2026.2684265","DOIUrl":"10.1080/15376516.2026.2684265","url":null,"abstract":"<p><p>Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker for oxidative DNA damage, is commonly used to assess the repair of reactive oxygen species (ROS) induced DNA damage. This study developed predictive models to quantify 8-OHdG concentrations in urine samples based on demographic and exposure-related variables from metal workers (21.27 ng/ml) and controls (12.63 ng/ml) using ELISA and machine learning algorithms. Three models; Random Forest Regressor (RFR), Support Vector Machine Regressor (SVMR), and Gradient Boosting Regressor (GBR) were evaluated for their predictive performance using metrics like Mean Squared Error (MSE), Root Mean Squared Error (RMSE), R-squared (R²), Mean Absolute Error (MAE), and classification metrics including Accuracy, Precision, Recall, and F1 Score. The RFR emerged as the best regression model with an MSE of 1.35, RMSE of 1.16, R² of 0.92, and precision of 0.89 where feature importance analysis indicated exposure and age as key predictors. The SVMR showed slightly lower performance (MSE = 1.54, R² = 0.91, precision = 0.83). GBR had reduced regression performance (MSE = 1.66, RMSE = 1.29, R² = 0.90) but achieved superior classification metrics all at 0.89. Overall, RFR provided the most accurate predictions, while GBR excelled in balancing classification performance. These findings indicated the efficiency of machine learning in quantifying oxidative stress biomarkers.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1388-1399"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148164509","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":"Analysis of persistent organic pollutants (organochlorine pesticides & PCBs) in livers of leatherback sea turtles (<i>Dermochelys coriacea</i>) by GC-MS/MS.","authors":"Andreas F Lehner, Mark Bokhart, John P Buchweitz, Raschelli A E Linz, Justin R Perrault","doi":"10.1080/15376516.2026.2677637","DOIUrl":"10.1080/15376516.2026.2677637","url":null,"abstract":"<p><p>Persistent organic pollutants (POPs) including chlorinated pesticides (OCPs) and polychlorinated biphenyls (PCBs) are among anthropogenic toxicological stressors of endangered leatherback sea turtles (<i>Dermochelys coriacea</i>). We examined livers from 17 juvenile-to-adult leatherbacks stranded along the North American east coast (2005-2014). We employed GC-MS/MS combined with an existing OCP method while validating new PCB methods, one based on Aroclor 1260 as an analytical standard and another based on specific PCB congeners (#52, 101, 118, 153, 138, 187, 183, 126, 180, 170). Validation covered linearity, limits of detection/quantitation, accuracy, precision and specificity. OCPs were found on a dry weight basis as: trans-nonachlor (<i>n</i> = 3), trans-chlordane (<i>n</i> = 5), cis-chlordane (<i>n</i> = 9), p,p'-DDE (<i>n</i> = 10), aldrin (<i>n</i> = 6) and dieldrin (<i>n</i> = 7). All bore PCBs. Those with the aldrin metabolite dieldrin had dieldrin/aldrin ratios > 1.0 indicating historical exposure. The Aroclor-based PCB method reported on total PCB exposure at concentrations averaging 46 ± 28 ppb with predominance of hexa-, hepta-, and pentachlorobiphenyls, indicating possible acquisition of the PCBs in mid-oceanic latitudes. The congener-specific approach showed the greatest prevalence of PCB #153 (16 of 16 samples). Nevertheless, the total concentration results of the two PCB methods correlated with one another as shown for heptachlorobiphenyls with a correlation coefficient of 0.826 (<i>p</i> < 0.001). Overall, the leatherbacks showed universal exposure to PCBs, while 12 of 17 carried between one and five of the OCPs, similar to findings of other researchers.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1341-1363"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148017446","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":"Choriocapillaris and blood flow alterations in smokers naïve to heated tobacco products: a cross-sectional study.","authors":"Marcella Nebbioso, Francesca Calzolaio, Valentina Castellani, Magda Gharbiya, Simona Bartimoccia, Giuseppe Biondi-Zoccai, Giacomo Frati, Giovanni Enrico Casciaro, Roberto Carnevale, Lorenzo Loffredo, Mattia D'Andrea, Annarita Vestri, Alessandro Avitabile, Vincenza Maria Elena Bonfiglio","doi":"10.1080/15376516.2026.2678476","DOIUrl":"10.1080/15376516.2026.2678476","url":null,"abstract":"<p><strong>Purpose: </strong>Heated tobacco products (HTPs) are devices that heat tobacco to high temperatures, rather than combusting it to generate smoke. The potential impact of HTPs on the body is not yet fully understood, as they are relatively recent products. The aim of this multidisciplinary study was to evaluate potential associations between the use of HTPs and both general and system-specific vital parameters in the enrolled subjects in order to determine whether these devices may be harmful and capable of inducing clinical, biochemical, or functional alterations compared to nonsmokers (non-SMs).</p><p><strong>Materials and methods: </strong>In this pilot study, the population consisted of 18 exclusive HTP users and 10 non-SMs. Spirometry was performed to assess respiratory function and blood sampling was used to evaluate the presence of oxidative stress (OS) biomarkers. Hemostatic variations and platelet aggregation were assessed using the total thrombus formation analysis system (T-TAS). Finally, ophthalmological examinations and optical coherence tomography angiography (OCTA) were performed to analyze the structural characteristics and chorioretinal vascular flow parameters.</p><p><strong>Results: </strong>Hemorheological parameters revealed accelerated thrombus formation and prolonged thrombus stability on T-TAS, along with increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2), or NADPH oxidase 2, levels. OCTA also revealed a statistically significant reduction in choriocapillaris flow (Ch-Flow) in HTP users.</p><p><strong>Conclusions: </strong>Alterations in primary hemostasis, OS, and chorioretinal microvascular perfusion highlight the need for further research in a larger cohort with higher mean age and longer cumulative exposure to HTPs to confirm these preliminary findings.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1364-1378"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148017466","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}