Toxicology Mechanisms and Methods最新文献

{"title":"Clinical and safety outcomes associated with aristolochic acid exposure: a systematic review and meta-analysis.","authors":"Ting Cui, Shumei Che, Xingxu Yan, Rongrong Yang, Zhenna Xu, Sijia Liu, Ying Li, Chenyu Hao, Junhan Jiang, Lili Song, Hua Jin, Yubo Li","doi":"10.1080/15376516.2025.2457340","DOIUrl":"10.1080/15376516.2025.2457340","url":null,"abstract":"<p><p>Current studies have clearly shown that aristolochic acid (AA) exposure can induce a variety of diseases, such as kidney disease, liver cancer, and urinary tract cancer (UTC). However, no studies have systematically analyzed and integrated these results. Therefore, we aimed to elucidate the association between AA exposure and the risk of safety outcomes for AA-related overall disease and different types of disease it causes. We conducted an exhaustive search of PubMed, EMBASE, Web of Science, and the Cochrane Library for relevant material up to April 2024. For AA-related overall disease, AA exposure was significantly associated with an increased incidence of AA-related overall disease (OR: 1.289, 95% CI: 1.183-1.404). For different types of disease, AA exposure was significantly associated with increased incidence of kidney disease (OR: 1.279, 95% CI: 1.029-1.590), UTC (OR: 1.842, 95% CI: 1.376-2.465), and liver cancer (OR: 1.146, 95% CI: 1.040-1.262). No significant association was found between AA exposure and the incidence of brain disease (OR: 1.161, 95% CI: 0.989-1.362). This study systematically analyzed various safety outcomes associated with AA exposure to provide a solid scientific basis for future prevention strategies and clinical management.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"513-523"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024807","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":"Sentinel role of military dogs in detecting genotoxic agents in the environment during military operations: a pilot study.","authors":"Lorenzo Tidu, Stefano Ciccarelli, Stefania De Sanctis, Florigio Lista, Rosaria Ferreri, Elisa Regalbuto, Fabio Grizzi, Gianluigi Taverna, Alessandro Poli, Marco Bruzzone, Marcello Ceppi, Paola Roggieri, Claudia Bolognesi","doi":"10.1080/15376516.2025.2453731","DOIUrl":"10.1080/15376516.2025.2453731","url":null,"abstract":"<p><p>During out-of-area military operations, the presence of carcinogenic and/or genotoxic agents has been reported, posing potential health risks to deployed soldiers. Military working dogs (MWDs), trained to detect explosives in the same environments as soldiers, could also serve as sentinel animals, providing valuable information on exposure to hazardous agents. These dogs can help identify environmental and potential adverse effects on their health and that of their handlers, possibly before relevant pathologies manifest. This study aims to evaluate the effectiveness of 33 Italian Army MWDs, deployed to the Lebanese theater for six consecutive months from October 2013 to January 2015, as sentinel animals for detecting exposure to genotoxic agents. The Cytokinesis-Block MicroNucleus (CBMN) assay was used to assess DNA damage, cytostasis, and cytotoxicity in the lymphocytes of these dogs. DNA damage events were specifically scored in once-divided binucleated cells (BCs) and included: a) micronuclei (MNi), indicative of chromosome breakage and/or whole chromosome loss; b) nucleoplasmic bridges (NPBs), a marker of DNA misrepair and/or telomere end-fusions; and c) nuclear buds (NBUDs), which signal the elimination of amplified DNA and/or DNA repair complexes. Our findings revealed an increase in chromosomal damage, assessed before and after deployment, with a statistically significant rise in MNi frequency, thus supporting the use of MWDs as sentinels for human exposure to hazardous agents.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"483-491"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012055","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":"Simultaneous measurement of fentanyl, fentanyl analogues and other drugs of abuse by multiplex bead assay.","authors":"J P Smith, M Alexander-Scott, C Striley, D Sammons","doi":"10.1080/15376516.2025.2457336","DOIUrl":"10.1080/15376516.2025.2457336","url":null,"abstract":"<p><p>Quantification of illicit drugs and controlled substances, in urine or as surface contamination, is often performed using expensive analytical techniques such as liquid chromatography with tandem mass spectrometry (LC-MS/MS). A time and cost-effective semi-quantitative surface-wipe and urine screening multiplex immunoassay for fentanyl and its analogues was developed in this investigation. We previously created a surface wipe multiplex immunoassay for methamphetamine, caffeine, cocaine, tetrahy-drocannabinol (THC) and oxycodone. This fluorescent covalent microsphere immunosorbent assay (FCMIA) is a competitive assay where drugs compete with protein-drug conjugates attached to microspheres for antibodies. It was assembled using a commercially available fentanyl antibody and protein-conjugate. Surface recovery from ceramic tiles was assessed by FCMIA, with results ranging from 26% for fentanyl to 60% for methamphetamine. Only fentanyl and its structurally similar analogues showed significant response to the fentanyl assay whereas, analogues structurally similar to carfentanil gave no response. Non-fentanyl drug assays did not appreciably detect fentanyl or its analogues. Overall, this method is a useful tool for assessing surface contamination and the effectiveness of decontamination by multiple drugs of abuse, potentially lowering workplace exposures. To broaden applicability, different antibodies or aptamers must be developed to detect structural differences found in classes of analogues such as carfentanil.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"502-512"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068281","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":"Advancements in heavy metal detection using microneedle array technology.","authors":"Robert M Taylor, Abdul-Mehdi S Ali, Yiliang Zhu, Alicia M Bolt, Justin T Baca","doi":"10.1080/15376516.2025.2461647","DOIUrl":"10.1080/15376516.2025.2461647","url":null,"abstract":"<p><p>Heavy metal and metalloid (HM) exposure poses significant health risks, including cardiovascular disease, cancer, and renal damage. This contamination, prevalent in the Western US, involves arsenic (As), cadmium (Cd), uranium (U), and vanadium (V). Interstitial fluid (ISF) is a source of biomarkers, which can be minimally invasively collected using microneedle array (MA) technology. Our study hypothesized that MA-extracted ISF would facilitate noninvasive HM quantification. We established analytical parameters for HM detection in ISF using inductively coupled plasma-mass spectrometry (ICP-MS), defined baseline ISF HM concentrations in unexposed animal populations, and monitored HM levels in ISF under mixed exposure in animal models. Additionally, we assessed HM levels in ISF and biological fluids from three human subjects. Thirty-six Sprague-Dawley rats were divided into cohorts: low-level mixed HMs exposure (5X maximum contaminant level (MCL)); high-level single HM with low-level others (50X MCL for one HM with 5X for others); and unexposed controls. ISF and plasma were collected weekly for 8 weeks and analyzed <i>via</i> ICP-MS. Our findings reveal a correlation between ISF and plasma HM levels, underscoring ISF's potential for real-time monitoring of HM exposure. This study also establishes baseline ISF HM levels, illustrating the feasibility of HM quantification using small ISF volumes.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"540-550"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12133419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brij 35 inhibited the CYP2E1-mediated metabolism and P-gp mediated transport of paracetamol in rats and <i>in vitro</i> models: amelioration of paracetamol toxicity.","authors":"Nagabhushanam Chunduru, Ravindra Babu Pingili, Vijaya R Dirisala, Prasad K","doi":"10.1080/15376516.2025.2457331","DOIUrl":"10.1080/15376516.2025.2457331","url":null,"abstract":"<p><p>The harmful by-product of paracetamol is known as N-Acetyl-p-benzoquinoneimine, (NAPQI). When paracetamol is given at therapeutic dosages or in excess, it undergoes Phase I metabolism in the liver <i>via</i> Cytochrome P-450 2E1 (CYP2E1), and then it produces NAPQI. Previous studies reported that a nonionic surfactant known as Brij 35 (Polyoxyethylene lauryl ether) has been shown to be an effective inhibitor of CYP2E1 and P-glycoprotein (P-gp). Hence, this <i>in vitro</i> and <i>in vivo</i> investigation set out to assess Brij 35 impact on paracetamol CYP2E1-mediated metabolism. For the <i>in vitro</i> investigation, isolated rat hepatocytes were used. Male Wistar rats were used for <i>in vivo</i> studies. There were 30 rats in total, with six individuals each group distributed among the five groups. The first group animals received 0.5% sodium carboxy methyl cellulose (control group); the second group animals treated with 300 mg/kg of paracetamol; the third group animals treated with Brij 35 (5 mg/kg) along with 300 mg/kg of paracetamol; the fourth group animals treated with 10 mg/kg of Brij 35 along with 300 mg/kg of paracetamol, and the fifth group animals treated with 20 mg/kg of Brij 35 along with 300 mg/kg of paracetamol for consecutive 21 days. The current study found that paracetamol plasma concentrations were much higher and NAPQI plasma concentrations were much lower when Brij 35 was co-administered may be due to inhibition of CYP2E1-mediated metabolism and P-gp-mediated intestinal transport of paracetamol. Brij 35 also reduced the increased hepatic and renal markers with significant hepatoprotective and nephroprotective changes in the histopathological investigation.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"492-501"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012090","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 analysis reveals molecular mechanisms associated with noise exposure to multiple diseases.","authors":"Maria Taboada-Alquerque, Jesus Olivero-Verbel","doi":"10.1080/15376516.2025.2460591","DOIUrl":"10.1080/15376516.2025.2460591","url":null,"abstract":"<p><p>Noise pollution is recognized as an environmental stressor that affects various biological processes beyond auditory functions, mainly through stress hormones release. This work explored the biological processes, diseases attributable to noise-regulated targets, and the main targets involved in each disease, employing a network toxicology approach. Through various databases and bioinformatics analysis, a total of 577 targets were identified as potential candidates implicated in diseases related to noise exposure, 10 from the GEO database and the rest from other databases. Noise pollution was found to regulate processes such as hormone response, cellular response to cytokines, and circulatory system functions, contributing to the development of the pathological manifestations related to the diseases like hypertension, ischemia, atherosclerosis, and cirrhosis. Hub targets for ischemia included IL-6, CASP3, AKT1, and TNF-α, while NOS3 was related to hypertension, and NOS3, TNF-α, AGT, and IL-1B to atherosclerosis. The targets were found to be linked to vascular regulation and inflammation in cardiovascular and cerebrovascular diseases. Molecular docking studies indicated stress hormones released by noise exposure regulates these diseases through signaling pathways, without implicating its direct binding to hub targets. The results indicate that individuals with vascular diseases are more vulnerable to the effects of prolonged noise exposure.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"524-539"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081143","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":"Quantitative methods for the risk assessment of drinking water contact chemicals following the NSF/ANSI/CAN 600 standard - part I: general methods.","authors":"Bradley J Lampe, Shannon Cousineau, J Caroline English, Shannon Ethridge, Lynne T Haber, Kristin Kerstens, Craig Rowlands, Kelly A Magurany","doi":"10.1080/15376516.2025.2463487","DOIUrl":"10.1080/15376516.2025.2463487","url":null,"abstract":"<p><p>Health-based criteria have been developed using quantitative methods for over 370 unregulated chemicals that have been detected in extraction testing of products certified or undergoing certification to public health-based drinking water standards. These criteria are derived in accordance with the requirements of NSF/ANSI/CAN 600, <i>Health Effects Evaluation and Criteria for Chemicals in Drinking Water</i> and undergo external peer review by an independent Health Advisory Board. However, a complete and unified description of how these criteria are derived is not available in the scientific literature. This is the first part of a two-part publication that describes the core concepts involved in deriving these criteria. In this first part, general approaches that are consistently applied to the derivation of health-based criteria are discussed, including methods related to the literature search, evaluation of study quality, derivation of the reference dose, selection of uncertainty factors, and identification of the appropriate drinking water intake rate.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"467-482"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524524","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":"Third party product certification for drinking water health effects.","authors":"Kathryn Foster, Kristin Licko","doi":"10.1080/15376516.2023.2216289","DOIUrl":"10.1080/15376516.2023.2216289","url":null,"abstract":"<p><p>Third-party certification to drinking water product consensus standards is how products for potable water systems are deemed suitable for public health and safety in North America. Drinking water product consensus standards are a type of standard developed through a process that includes participation from expert volunteers and requires general agreement from all stakeholders. Certification to drinking water product consensus standards is required <i>via</i> plumbing codes and state or local regulations in most of the United States and Canada, making third-party certification essential for products intended for sale and installation in North America. Third-party certification bodies (CBs) test and certify products to these drinking water product consensus standards through an evaluation process that includes a thorough review of each product's composition, laboratory testing, and inspection of each facility where the product is manufactured. Products that comply with the consensus standard requirements are entitled to bear a certification mark that demonstrates their suitability for use in potable water systems. Drinking water product standards developed by NSF reference NSF/ANSI/CAN 600: <i>Health Effects Evaluation and Criteria for Chemicals in Drinking Water</i> for the toxicological criteria to evaluate chemical leachates derived from material extraction testing. Here, we review the third-party product certification process for evaluating products used in potable water systems and describe how the certification process relies on the health effects criteria and toxicological evaluation procedures described in NSF/ANSI/CAN 600.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"445-449"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9540642","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 heterogeneity in pediatric sepsis: identification of oxidative stress-related subtypes and diagnostic biomarkers through integrated bioinformatics analysis.","authors":"Ding Ding, Min Zhang, Zhen Li, Zhengxiang Liu, Nian Liu","doi":"10.1080/15376516.2025.2466577","DOIUrl":"10.1080/15376516.2025.2466577","url":null,"abstract":"<p><strong>Background: </strong>Pediatric sepsis is a life-threatening condition characterized by a dysregulated immune response to infection, often involving heightened oxidative stress. Understanding the molecular heterogeneity of sepsis can provide insights into potential therapeutic targets and diagnostic biomarkers.</p><p><strong>Methods: </strong>Machine learning approaches were employed to identify diagnostic biomarkers. Unsupervised clustering was performed to identify distinct sepsis subtypes. We conducted an integrative analysis combining Gene Set Variation Analysis (GSVA), Gene Set Enrichment Analysis (GSEA), differential gene expression, and functional enrichment to study oxidative stress-related subgroups in sepsis patients. Immune cell infiltration and immune-related pathway activities were analyzed using the ssGSEA algorithm. GSVA and GSEA indicated significant enrichment of oxidative stress-related pathways in sepsis patients compared to controls.</p><p><strong>Results: </strong>Differential expression analysis identified 371 upregulated and 304 downregulated genes in sepsis, with 34 genes linked to oxidative stress. LASSO and Random Forest analyses highlighted key diagnostic genes (GBA and MGST1), validated in independent datasets (GSE13904) with high diagnostic accuracy (AUC: GBA = 0.924, MGST1 = 0.857). Unsupervised clustering revealed two distinct sepsis subtypes with differential immune cell infiltration and pathway activities: Subtype 1 showed higher T cell and TFH infiltration, while Subtype 2 exhibited increased macrophage infiltration. Functional enrichment and GSEA identified key metabolic, oxidative stress, and immune pathways that were enriched in Subtype 2.</p><p><strong>Conclusion: </strong>Our comprehensive bioinformatics analysis unveils significant oxidative stress-related molecular heterogeneity in sepsis, identifying potential diagnostic biomarkers and therapeutic targets. Personalized medicine approaches targeting specific oxidative stress pathways and immune responses could enhance sepsis management and patient outcomes.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"551-563"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415343","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":"Development of a gradual hypoxia chamber for assessing copper toxicity on air-breathing behavior in <i>Lymnaea stagnalis</i>.","authors":"Lauren Zink, Chris M Wood","doi":"10.1080/15376516.2024.2449417","DOIUrl":"https://doi.org/10.1080/15376516.2024.2449417","url":null,"abstract":"<p><p>Behavioral endpoints are of increasing interest in toxicology because of their sensitivity, but require clear guidance for experimental design. This study describes the design of a hypoxia chamber for use with pond snails, <i>Lymnaea stagnalis</i>. Studies assessing the switch from water- to air-breathing in hypoxic conditions have previously utilized methods that neglect intricacies of animal behavior such as handling stress and acclimation. The chamber provides a linear decline in dissolved oxygen, against which surfacing behavior for air-breathing can be precisely measured. The maximum biomass of snails suitable for use in the hypoxia chamber, such that the nitrogen-driven deoxygenation curve is not altered by the snails' own metabolism, was established to be greater than 10 adult snails. The capacity of most analysis softwares is below accurately tracking 10 individuals at once, indicating this is likely not a limitation. The size of snails determined the amount of time each episode of aerial respiration was, with smaller snails spending more time air-breathing. A proof-of-principle experiment using acute copper exposure (0 - 60 µg/L) yielded a concentration-response curve, with greater copper concentrations inhibiting air-breathing. The chamber described in the present study provides an improved framework for assessing hypoxic response and is presented in a manner allowing for further modification to meet unique research needs.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"35 4","pages":"422-429"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028415","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}