Toxicology Research最新文献

{"title":"Agent-specific DNA repair kinetic in 3T3 cells: a comparative study using the in vitro comet assay.","authors":"Seda İpek Tekneci, Aylin Üstündağ, Yalçın Duydu","doi":"10.1093/toxres/tfaf180","DOIUrl":"10.1093/toxres/tfaf180","url":null,"abstract":"<p><p>Alkaline comet assay is a widely used technique for assessing DNA damage and repair at the single-cell level. However, the lack of standardized protocols, particularly for <i>in vitro</i> applications, makes it difficult to reproduce and compare the results from different laboratories. This study aimed to evaluate time-dependent DNA repair kinetics in 3T3 cells following exposure to six commonly used genotoxic agents, hydrogen peroxide (H₂O₂), potassium bromate (KBrO₃), ethyl methanesulfonate (EMS), methyl methanesulfonate (MMS), N-ethyl-N-nitrosourea (ENU), and etoposide (EP). The cells were subjected to concentrations and exposure durations previously determined to induce maximum DNA damage. DNA repair was subsequently assessed at various intervals over a 24-h duration utilizing the comet assay. Each agent displayed a unique repair profile based on the type of DNA damage generated and cellular repair mechanisms involved. H₂O₂ and EMS induced rapid repair, whereas ENU- and EP-induced lesions were more persistent. These findings underscore the critical role of time as a variable in comet assay-based DNA repair assessments, contributing valuable reference data to support the standardization and validation of this assay for genotoxicity testing.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 6","pages":"tfaf180"},"PeriodicalIF":2.1,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12702454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145761625","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":"Emerging insights into the relationship between ERS and autophagy in toxic damage caused by endocrine-disrupting chemicals.","authors":"Jiahong Chen, Liying Li, Mengdan Liu, Chenghui Wang, Yujing Zhang","doi":"10.1093/toxres/tfaf175","DOIUrl":"https://doi.org/10.1093/toxres/tfaf175","url":null,"abstract":"<p><p>Endocrine-disrupting chemicals (EDCs), ubiquitous in the environment, are increasingly recognized for their detrimental effects on human health. Chronic exposure to EDCs disrupts essential physiological systems, particularly those regulating reproductive, neurological, and metabolic homeostasis. Furthermore, growing evidence suggests a correlation between EDCs exposure and tumorigenesis. Endoplasmic reticulum stress (ERS) has emerged as a vital cellular response to toxic stimuli, influencing apoptotic and proliferative pathways. Notably, ERS and autophagy are interconnected stress responses implicated in various pathological conditions. We propose that EDCs exert their toxic effects and facilitate disease progression by disrupting the ERS-autophagy signaling axis. This review critically examines the molecular interactions between ERS and autophagy induced by EDCs exposure, with the aim of advancing mechanistic understanding and identifying novel therapeutic targets for diseases associated with EDCs.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 6","pages":"tfaf175"},"PeriodicalIF":2.1,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12700166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145754895","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":"Formulation, characterization, and toxicological evaluation of quinestrol-loaded nanoparticles for extended oral contraceptive efficacy in rodent pest management.","authors":"Dimple Mandla, Neena Singla, Anu Kalia","doi":"10.1093/toxres/tfaf176","DOIUrl":"https://doi.org/10.1093/toxres/tfaf176","url":null,"abstract":"<p><p>Fertility control of rodents offers a promising alternative strategy, providing a long-term solution by gradually reducing the rodent population through controlled reproduction. Quinestrol, a synthetic estrogen, can potentially mitigate rodent fertility, but its lower bioavailability in the body limits its effectiveness. In this study, we prepared polymeric nanoparticles using standard polymer-based encapsulation techniques. This study aims to formulate, characterize, and evaluate quinestrol-based poly (lactic-co-glycolic acid) (PLGA) nanoparticles to enhance the bioavailability and contraceptive efficacy of quinestrol in rodents over extended periods. Blank PLGA nanoparticles (PNP) and those loaded with quinestrol (QNP) were successfully formulated using the emulsion-evaporation method and characterized for size, zeta potential, release kinetics and stability. The study further evaluated the toxicological impact of these nanoparticles on reproductive hormones in female rats (<i>Bandicota bengalensis</i>), measured using ELISA, and administered orally through cereal-based ready-to-use baits containing bulk quinestrol (QB-B) and QNP (QNP-B). Successful encapsulation yielded QNP (337.93 ± 6.51 nm), smaller than PNP (354.33 ± 3.87 nm), with a 13.42% drug loading. Low PDI (<0.3) confirmed uniform size. Drug release involved an initial burst followed by slow release up to 96 h. Quinestrol in both QNP-B (10 ppm) and QB-B (100 ppm) increased estradiol (11.59 to 32.38-41.13 pg/mL) and progesterone (4.70 to 14.42-18.25 ng/mL), while reducing FSH (0.94 to 0.42-0.45 mIU/mL) and LH (28.15 to 17.60-18.69 mIU/mL) after 15 days. QNP-B effects lasted 75 days, compared to 45 days for QB-B, demonstrating the prolonged efficacy of QNP and supporting PLGA-based delivery as a promising approach for sustained rodent fertility control.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 6","pages":"tfaf176"},"PeriodicalIF":2.1,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12679284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699486","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":"Computational genomics of zebrafish under micro- and Nanoplastic stress: identification of pathways and hub genes.","authors":"Rajesh Pamanji, Ragothaman Prathiviraj, Gisha Sivan, Srikanth Koigoora","doi":"10.1093/toxres/tfaf172","DOIUrl":"https://doi.org/10.1093/toxres/tfaf172","url":null,"abstract":"<p><p>This review synthesizes in silico evidence on the toxicological effects of microplastics (MPs) and nanoplastics (NPs) in zebrafish (<i>Danio rerio</i>). With the increasing prevalence of these pollutants in aquatic ecosystems, evaluating their molecular impacts is essential for risk assessment. We systematically mined toxicogenomic studies from PubMed, Scopus, and Web of Science and applied network biology approaches to identify gene-gene interactions underlying micro- and nanoplastic (MNP) toxicity. Using STRING for protein-protein interaction mapping and Cytoscape with cytoHubba for hub-gene detection, we identified casp3a, casp3b, bcl2a, tp53, and nfe2l2a as central regulators of stress responses. Enrichment analyses linked these genes to oxidative stress, apoptosis, inflammatory signalling, and transcriptional dysregulation, pathways implicated in cardiotoxic, neurotoxic, reproductive, and developmental outcomes. While zebrafish provide a relevant vertebrate model, the present findings are derived exclusively from computational analyses and require experimental validation. By integrating toxicogenomics with network-based approaches, this review provides mechanistic insights into MNP-induced perturbations in zebrafish and highlights molecular pathways that may mediate broader ecological and human health risks.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 6","pages":"tfaf172"},"PeriodicalIF":2.1,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12679283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699455","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":"Protective effect of aqueous extract of <i>Myrica Esculenta</i> against cyclophosphamide-induced spermatogenesis dysfunction in Wistar rats via antioxidant Signaling pathway.","authors":"Nitesh Parsaila, Archana M Navale, Ajay B Shelke, Nishant Patidar, Dinesh Sharma, Sagar Shinde, Bikash Mishra, Snehal M Singh, Jhanvi Soni","doi":"10.1093/toxres/tfaf173","DOIUrl":"10.1093/toxres/tfaf173","url":null,"abstract":"<p><p>Oligospermia is a severe disorder that affects the male population around the world. Genetic defects, smoking, age, and modern lifestyle are significant contributing factors to male infertility in oligospermia. <i>Myrica esculenta</i> fruits contain high levels of chlorogenic acid, caffeic acid, myricetin, quercetin, and ascorbic acid, which have antioxidant, anti-inflammatory, and pharmacological properties. Therefore, the present study evaluates the protective effects of <i>Myrica esculenta</i> aqueous extract against cyclophosphamide (CYP)-induced spermatogenic dysfunction in rats. A total of 25 Wistar rats were divided into five groups, each group consisting of 5 animals; 1) normal control (saline 5 mL/kg), 2) CYP (30 mg/kg, i.p.), 3) clomiphene citrate (0.25 mg/kg/i.p.), 4) aqueous <i>Manihot esculenta</i> extract (250 mg/kg/p.o.), 5) aqueous <i>M. esculenta</i> extract (500 mg/kg/p.o.). Treatment was given once a day for 15 days continuously. Our observation found a significant improvement in total sperm count, viability, motility, and a decline in abnormal sperm generation in <i>M. esculenta</i> extract 250 and 500 mg/kg treatment groups as compared to CYP-treated Wistar rats. Moreover, <i>M. esculenta</i> extract shows a significant increase in the 3β-HSD, 17β-HSD, GSH, and catalase, and reduces the oxidative stress, thereby improving the sperm quality. <i>M. esculenta</i> extract was found to reduce DNA fragmentation and restore the testicular composition by enhancing the number of spermatogonia and Sertoli cells in test-treated rats as compared to disease control rats. <i>M. esculenta</i> extract also improved sperm quality, boosted testosterone, and reduced oxidative stress, protecting against oligospermia. These findings highlight its therapeutic potential in managing male infertility. However, further investigations are necessary to elucidate the precise molecular mechanisms underlying its protective effects.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 6","pages":"tfaf173"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12667274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145659932","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":"Response to Kanchan, et al.","authors":"Omar De Santi, Marcelo Orellana, Cecilia Andrea Di Niro, Vanina Greco","doi":"10.1093/toxres/tfaf171","DOIUrl":"10.1093/toxres/tfaf171","url":null,"abstract":"","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 6","pages":"tfaf171"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12667275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145659947","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":"Strict adherence to inclusion criteria: an essential step in systematic reviews and meta-analyses.","authors":"Prins Kumar Agrawal, Apoorva Gupta, Pulagura Siva Sai Kumar, Tanuj Kanchan","doi":"10.1093/toxres/tfaf170","DOIUrl":"10.1093/toxres/tfaf170","url":null,"abstract":"","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 6","pages":"tfaf170"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12667256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145659978","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":"Di (2-ethylhexyl) phthalate induces cholestasis liver injury in mice associated with promoting macrophage polarization through NRF2 signaling pathway.","authors":"Yun Yu, Lun Zhang, Jing Zhou, Jianqing Wang, Qianqian Huang","doi":"10.1093/toxres/tfaf151","DOIUrl":"https://doi.org/10.1093/toxres/tfaf151","url":null,"abstract":"<p><p>Diethylhexyl phthalate (DEHP) as a common environmental pollutant has toxic effects on a variety of biological systems, including liver toxicity and immunotoxicity. Previously we had demonstrated that DEHP cause cholestatic liver injury, but whether macrophages play a role in this is unclear, and few studies have focused on the direct effects of DEHP on macrophages. Therefore, this study investigated whether DEHP affects macrophages in vivo and the mechanism by which DEHP regulates macrophages in vitro. The results showed that DEHP induced cholestatic liver injury by up-regulating TBA levels of serum and liver. Simultaneously, DEHP increased the number of F4/80 positive macrophages and promoted the transcriptional level of IL-1β and IL-6 in liver tissue. Further in vitro, We found that DEHP decreased M2 macrophage marker Arg1 level and increased the levels of M1 macrophage marker iNOS, accompanied by up-regulation of the transcriptional levels of IL-1β, TNF-α and CCl₂. Moreover, DEHP increased glycolytic flux, which was confirmed by the increased Glut1, HK2 and pfkfb3 expression. Mechanistically, we found DEHP inhibited NRF2 activation, and down-regulated the expression of downstream target NOQ1. While, CDDO (an NRF2 activator) could abrogate the promotion of DEHP on M1 macrophage polarization and glycolysis. These findings indicated that promotion effect of DEHP on M1 macrophage polarization is associated with regulating energy metabolism of macrophages through NRF2/NQO1 pathway.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 6","pages":"tfaf151"},"PeriodicalIF":2.1,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12661938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145646888","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":"Aluminum toxicity: a comprehensive narrative review.","authors":"Pavitra Behra, Monika Bhadauria, Satendra Kumar Nirala","doi":"10.1093/toxres/tfaf167","DOIUrl":"https://doi.org/10.1093/toxres/tfaf167","url":null,"abstract":"<p><p>Aluminum (Al) is a widely accessible environmental and industrial element that finds routes of exposure through inhalation of airborne particles, ingestion of contaminated food and water, dermal and medical applications. Chronic and acute exposure lead to systemic accumulation of Al that induce aluminum toxicity. Exposure to Al exerts diverse toxicological effects, including oxidative stress, immune dysregulation, genotoxicity, pro-inflammatory activity, protein misfolding, enzymatic inhibition, metabolic imbalance, membrane dysfunction and induction of apoptosis and necrosis. The Al toxicity is associated with a wide range of pathologies such as respiratory diseases, cardiovascular complications, gastrointestinal disorders, inflammation, hematologic, hepato-renal and neurodegenerative diseases and reproductive and developmental disorders, genotoxicity as well as endocrine and pancreatic necrosis. This comprehensive review narrates multifactorial nature of Al toxicity emphasizing role of reactive oxygen species in pathogenesis and significances of Al exposure in high-risk populations.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 6","pages":"tfaf167"},"PeriodicalIF":2.1,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12662758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145646847","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":"Deciphering spatial patterns of potential toxic elements using GIS and multivariate statistics for sustainable development in some areas of MENA region.","authors":"Mohamed Youssef, Abdelbaset S El-Sorogy, Sami Al Otaibi, Jose Emilio Meroño de Larriva, Mohamed S Shokr, Khaled Al-Kahtany","doi":"10.1093/toxres/tfaf166","DOIUrl":"https://doi.org/10.1093/toxres/tfaf166","url":null,"abstract":"<p><p>The current research aims to map the spatial distribution of potentially toxic elements (PTEs) (As, Co, Cr, Cu, Fe, Mn, Ni, V, and Zn) in Qena southern of Egypt, identify the sources of PTEs using geostatistical analysis (principal component analysis, cluster analysis, and correlation matrix(, and determine the level of contamination in the study area to assess soil contamination with selected potentially toxic elements. To accomplish this, thirty soil samples were gathered and examined for the PTEs. The variability of the soil chemical content was estimated using multivariate geostatistical analysis. All PTEs, with the exception of As, show a strong positive association with one another in the correlation matrix. Two components illustrated through the principal component analysis (PCA). The primary source of the first component, which accounts for the majority of the variance, is a combination of industrial activity and agricultural activities. It is rich in Co, Cr, Cu, Fe, Mn, Ni, V, and Zn. As is abundant in the second component, and lithology may be the source. According to the Pollution Load Index (PLI), 61% of the study area (west and south of the study area) was contaminated, and 31% of the study area (east of the study area) was unpolluted. The Degree of Contamination (DC) index was used to classify the research region as low, moderate, and considerably contaminated, with percentages of 21, 51, and 28% of the study area, respectively. The Nemerow Pollution Index (NPI) classifies the majority of samples (63.33%) as slightly to moderately polluted. The study's conclusions showed that to evaluate the potential risk to the environment, PTEs concentrations in the study area need to be monitored. This study aligns with key UN Sustainable Development Goals (SDGs), particularly SDG 3 (Good Health) and SDG 15 (Life on Land), by to safeguarding both human well-being and terrestrial ecosystem health. Moreover, the study provides a scientific basis for sustainable environmental management, supporting the transition towards safer and more resilient communities.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 6","pages":"tfaf166"},"PeriodicalIF":2.1,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12659701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145646894","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}