Toxicology Mechanisms and Methods最新文献

{"title":"Enhanced kidney damage induced by increasing nonylphenol doses: impact on autophagy-related proteins and proinflammatory cytokines in rats.","authors":"Betul Yalcın, Gozde Ozge Onder, Ozge Goktepe, Pınar Alisan Suna, Ozge Cengiz Mat, Eda Koseoglu, Emre Cetindag, Munevver Baran, Nazmiye Bitgen, Özlem Öz Gergı N, Arzu Yay","doi":"10.1080/15376516.2024.2358348","DOIUrl":"10.1080/15376516.2024.2358348","url":null,"abstract":"<p><p>Nonylphenol (NP) is an organic pollutant and endocrine disruptor chemical that has harmful effects on the environment and living organisms. This study looked at whether kidney tissues subjected to increasing doses of nonylphenol generated alterations in histopathologic, pro-inflammatory, and autophagic markers. Fifty rats were divided into five groups of ten each: group I: healthy group, II: control (corn oil), group III: 25 μl/kg NP, group IV: 50 μl/kg NP, group V: 75 μl/kg NP. The kidney tissue samples were obtained for histopathological, immunohistochemical, and biochemical analyses. The histological deteriorations observed in all NP groups included tubular epithelial cell degeneration, inflammation areas, and hemorrhage. The immunohistochemical investigations showed that NP significantly elevated the autophagy markers (Beclin-1, LC3A/B, p62), pro-inflammatory cytokines (TNF-α, IL-6), HIF-1α, and eNOS in group III, IV and V compared with group I and II. The biochemical analysis also revealed that pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) increased in correlation with the NP doses, but only IL-1β reached statistical significance in NP treated rats kidney tissue. The biochemical findings have been confirmed by the histological studies. The damage to renal tissue caused by NP exposure may worsen it by increasing inflammatory and autophagic markers.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"867-876"},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071971","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":"Effects of acute carbon monoxide poisoning on liver damage and comparisons of related oxygen therapies in a rat model.","authors":"Gul Sahika Gokdemir, Ugur Seker, Berjan Demirtas, Seyhan Taskin","doi":"10.1080/15376516.2024.2353887","DOIUrl":"10.1080/15376516.2024.2353887","url":null,"abstract":"<p><p>Acute carbon monoxide (CO) poisoning may cause liver damage and liver dysfunction. Therefore, in this study, we aimed to compare the efficiency of normobaric oxygen (NBO) and high-flow nasal cannula oxygen (HFNCO) treatments on liver injury. For that purpose, 28 male Wistar albino rats were divided into four groups (Control, CO, CO + NBO, and CO + HFNCO). The control group was allowed to breath room air for 30 min. Acute CO poisoning in CO, CO + NBO, CO + HFNCO was induced by CO exposure for 30 min. Thereafter, NBO group received 100% NBO with reservoir mask for 30 min. HFNCO group received high-flow oxygen through nasal cannula for 30 min. At the end of the experiment, all animals were sacrificed by cardiac puncture under anesthesia. Serum liver function tests were measured. Liver tissue total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) levels, tissue histomorphology and immunoexpression levels of Bax, Caspase 3, TNF-α, IL-1β, and NF-κB were also examined. Our observations indicated that acute CO poisoning caused significant increases in blood COHb, serum aminotransferase (AST), alanine aminotransferase (ALT0, alkaline phosphatase (ALP), total protein, albumin, and globulin levels but a decrease in albumin to globulin ratio (all, <i>p</i> < 0.05). Furthermore, acute CO poisoning significantly increased the OSI value, and the immunoexpresssion of Bax, Caspase 3, TNF-α, IL-1β, and NF-κB in liver tissue (all, <i>p</i> < 0.05). These pathological changes in serum and liver tissue were alleviated through both of the treatment methods. In conclusion, both the NBO and HFNCO treatments were beneficial to alleviate the acute CO poisoning associated with liver injury and dysfunction.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"845-854"},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899595","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":"Multiple-heated cooking oil promotes early hepatic and renal senescence in adult male rats: the potential regenerative capacity of oleuropein.","authors":"Esraa M Zakaria, Ebaa Mohammed, Amira Ebrahim Alsemeh, Asmaa Monir Eltaweel, Rania A Elrashidy","doi":"10.1080/15376516.2024.2365431","DOIUrl":"10.1080/15376516.2024.2365431","url":null,"abstract":"<p><p>For economic purposes, cooking oil is repeatedly heated in food preparation, which imposes serious health threats. This study investigated the detrimental effects of multiple-heated cooking oil (MHO) on hepatic and renal tissues with particular focusing on cellular senescence (CS), and the potential regenerative capacity of oleuropein (OLE). Adult male rats were fed MHO-enriched diet for 8 weeks and OLE (50 mg/kg, PO) was administered daily for the last four weeks. Liver and kidney functions and oxidative stress markers were measured. Cell cycle markers p53, p21, cyclin D, and proliferating cell nuclear antigen (PCNA) were evaluated in hepatic and renal tissues. Tumor necrosis factor-α (TNF-α) and Bax were assessed by immunohistochemistry. General histology and collagen deposition were also examined. MHO disturbed hepatic and renal structures and functions. MHO-fed rats showed increased oxidative stress, TNF-α, Bax, and fibrosis in liver and kidney tissues. MHO also enhanced the renal and hepatic expression of p53, p21, cyclin D and PCNA. On the contrary, OLE mitigated MHO-induced oxidative stress, inflammatory burden, apoptotic and fibrotic changes. OLE also suppressed CS and preserved kidney and liver functions. Collectively, OLE displays marked regenerative capacity against MHO-induced hepatic and renal CS, <i>via</i> its potent antioxidant and anti-inflammatory effects.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"936-953"},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284815","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":"Antiurolithiatic effect of triptonide in ethylene glycol-induced urolithiasis in rats.","authors":"Qiang Wang, Jinghong Zhang, Xiaosong Yin, Tongwei Liu, Chuangui Li, Haibo Yuan, Ding Li","doi":"10.1080/15376516.2024.2364882","DOIUrl":"10.1080/15376516.2024.2364882","url":null,"abstract":"<p><p>Urolithiasis is one of the most prevalent benign urological disorders globally with a high incidence rate. Male Sprague-Dawley rats were chemically induced to have urolithiasis and treated with triptonide and the standard antiurolithic drug cystone. Kidney weight was measured to detect calculi formation, and urinary parameters such as pH, 24-h urine volume, and protein content were measured to analyze the urolithiasis induction in rats. The inorganic ions, organic solutes, antioxidant levels, and inflammatory cytokines were measured in the experimental rats. Triptonide treatment significantly modulated the urinary pH, decreased the protein concentration, and increased the urinary outflow in urolithiasis induced rats. It also significantly decreased the urinary excretion of calcium and phosphorous and increased the excretion of magnesium, potassium, sodium, creatinine, and uric acid. SOD, CAT, and GPx levels were increased in triptonide-treated rats, and it significantly reduced the MDA levels. Triptonide treatment also decreased the levels of inflammatory cytokines and prevented the renal tissue from inflammation. To conclude, our results prove that triptonide significantly prevents calculi formation and protects renal tissue from urolithiasis-induced damage in rats. Further studies may prove triptonide a potent alternative to currently available antiurolithic drugs.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"926-935"},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141451545","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":"Silica-induced ROS in alveolar macrophages and its role on the formation of pulmonary fibrosis via polarizing macrophages into M2 phenotype: a review.","authors":"Shu-Ling Du, Yu-Ting Zhou, Hui-Jie Hu, Li Lin, Zhao-Qiang Zhang","doi":"10.1080/15376516.2024.2400323","DOIUrl":"10.1080/15376516.2024.2400323","url":null,"abstract":"<p><p>Alveolar macrophages (AMs), the first line against the invasion of foreign invaders, play a predominant role in the pathogenesis of silicosis. Studies have shown that inhaled silica dust is recognized and engulfed by AMs, resulting in the production of large amounts of silica-induced reactive oxygen species (ROS), including particle-derived ROS and macrophage-derived ROS. These ROS change the microenvironment of the AMs where the macrophage phenotype is stimulated to swift from M0 to M1 and/or M2, and ultimately emerge as the M2 phenotype to trigger silicosis. This is a complex process accompanied by various molecular biological events. Unfortunately, the detailed processes and mechanisms have not been systematically described. In this review, we first systematically introduce the process of ROS induced by silica in AMs. Then, describe the role and molecular mechanism of M2-type macrophage polarization caused by silica-induced ROS. Finally, we review the mechanism of pulmonary fibrosis induced by M2 polarized AMs. We conclude that silica-induced ROS initiate the fibrotic process of silicosis by inducing macrophage into M2 phenotype, and that targeted intervention of silica-induced ROS in AMs can reprogram the macrophage polarization and ameliorate the pathogenesis of silicosis.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-12"},"PeriodicalIF":3.2,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120690","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":"Leveraging new approach methodologies: ecotoxicological modelling of endocrine disrupting chemicals to Danio rerio through machine learning and toxicity studies.","authors":"Gopal Italiya, Sangeetha Subramanian","doi":"10.1080/15376516.2024.2400324","DOIUrl":"10.1080/15376516.2024.2400324","url":null,"abstract":"<p><p>New approach methodologies (NAMs) offer information tailored to the intended application while reducing the use of animals. NAMs aim to develop quantitative structure-activity relationship (QSAR) and quantitive-Read-Across structure-activity relationship (q-RASAR) models to predict and categorize the acute toxicity of known and unknown endocrine-disrupting chemicals (EDCs) against zebrafish. EDCs are a diverse group of toxic substances that disrupt the endocrine system of humans and animals. The q-RASAR model was constructed and verified using validation metrics (<i>R</i>² = 0.886 and <i>Q</i>² = 0.814) which found to be more reliable model compare to QSAR model. The substructure fingerprint was well-fitted for the classification model and it was validated using 10-fold average accuracy (<i>Q</i> = 86.88%), specificity (Sp = 88.89%), Matthew's correlation curve (MCC = 0.621) and receiver operating characteristics (ROC = 0.828). The dataset of unknown substances revealed that phenolphthalein (Php) exhibited a significant level of toxicity based on q-RASAR model. The docking and simulation study indicated that the computationally derived important features successfully bound to the target zebrafish sex hormone binding globulin (zfSHBG). The experimental LC50 value of 0.790 mg L^-1 was very close to the predicted value of 0.763 mg L^-1, which provides high confidence to the developed model.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-17"},"PeriodicalIF":3.2,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120689","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":"Unveiling the impact of estrogen exposure on ovarian cancer: A comprehensive risk model and immune landscape analysis.","authors":"Zhongna Yu,Weili Yang,Qinwei Zhang,Mengyu Zheng","doi":"10.1080/15376516.2024.2402865","DOIUrl":"https://doi.org/10.1080/15376516.2024.2402865","url":null,"abstract":"This study examines the impact of estrogenic compounds like bisphenol A (BPA), estradiol (E2), and zearalenone (ZEA) on human ovarian cancer, focusing on constructing a risk model, conducting Gene Set Variation Analysis (GSVA), and evaluating immune infiltration. Differential gene expression analysis identified 980 shared differentially expressed genes (DEGs) in human ovarian cells exposed to BPA, E2, and ZEA, indicating disruptions in ribosome biogenesis and RNA processing. Using the Cancer Genome Atlas Ovarian Cancer (TCGA-OV) dataset, a least absolute shrinkage and selection operator (LASSO)-based risk model was developed incorporating prognostic genes 4-Hydroxyphenylpyruvate Dioxygenase Like (HPDL), Thy-1 Cell Surface Antigen (THY1), and Peptidase Inhibitor 3 (PI3). This model effectively stratified ovarian cancer patients into high-risk and low-risk categories, showing significant differences in overall survival, disease-specific survival, and progression-free survival. GSVA analysis linked HPDL expression to pathways related to the cell cycle, DNA damage, and repair, while THY1 and PI3 were associated with apoptosis, hypoxia, and proliferation pathways. Immune infiltration analysis revealed distinct immune cell profiles for high and low expression groups of HPDL, THY1, and PI3, indicating their influence on the tumor microenvironment. The findings demonstrate that estrogenic compounds significantly alter gene expression and oncogenic pathways in ovarian cancer. The risk model integrating HPDL, THY1, and PI3 offers a strong prognostic tool, with GSVA and immune infiltration analyses providing insights into the interplay between these genes and the tumor microenvironment, suggesting potential targets for personalized therapies.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"180 1","pages":"1-15"},"PeriodicalIF":3.2,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142214524","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":"A critical insight into the physicochemical stability of macular carotenoids with respect to their industrial production, safety profile, targeted tissue delivery, and bioavailability.","authors":"Samudra P Banik,Pawan Kumar,Pijush Basak,Apurva Goel,Sunny E Ohia,Manashi Bagchi,Sanjoy Chakraborty,Arijit Kundu,Debasis Bagchi","doi":"10.1080/15376516.2024.2401924","DOIUrl":"https://doi.org/10.1080/15376516.2024.2401924","url":null,"abstract":"Lutein, zeaxanthin and mesozeaxanthin, collectively termed as macular pigments, are key carotenoids integral to optimized central vision of the eye. Therefore, nutraceuticals and functional foods have been developed commercially using carotenoid rich flowers such as marigold and calendula or single celled photosynthetic algae such as the Dunaliella. Industrial formulation of such products enriched in macular pigments have often suffered from serious bottlenecks in stability, delivery and bioavailability. The two chief factors largely responsible for decreasing the shelf-life have been solubility and oxidation of these pigments owing to their strong lipophilic nature and presence of conjugated double bonds. In this regard, oil-based formulations have often been found to be more suitable than powder-based formulations in terms of shelf life and targeted delivery. In some cases, addition of phenolic acids in the formulations have also augmented the product value by enhancing micellization. In this regard, a novel proprietary formulation of these pigments has been developed in our laboratory utilizing marigold extracts in a colloidal solution of extra virgin olive oil and canola oil fortified with antioxidants like thyme oil, tocopherol and ascorbyl palmitate. This review article presents an updated insight on the stability and bioavailability of industrially manufactured macular carotenoids together with their safety and solubility issues.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"59 1","pages":"1-26"},"PeriodicalIF":3.2,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142214526","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":"Establishing a link between the chemical composition and biological activities of <i>Gladiolus italicus</i> Mill. from the Turkish flora utilizing <i>in vitro</i>, <i>in silico</i> and network pharmacological methodologies.","authors":"Gokhan Zengin, Mehmet Veysi Cetiz, Nurgul Abul, Ilhami Gulcin, Giovanni Caprioli, Diletta Piatti, Massimo Ricciutelli, Ismail Koyuncu, Ozgur Yuksekdag, Muammer Bahşi, Osman Güler, Muhammad Zakariyyah Aumeeruddy, Mohamad Fawzi Mahomoodally","doi":"10.1080/15376516.2024.2397387","DOIUrl":"https://doi.org/10.1080/15376516.2024.2397387","url":null,"abstract":"<p><strong>Objectives: </strong>Five solvent extracts (n-hexane, ethyl acetate, ethanol, ethanol/water (70%), and water) of <i>Gladiolus italicus</i> Mill. from Turkey were evaluated for chemical and biological properties.</p><p><strong>Methods: </strong>Antioxidant activities, inhibitory properties against key enzymes involved in the etiology of chronic diseases were tested, as well as cytotoxic effects on different cell lines. Chemical characterization was also carried out to determine the most abundant compounds of each extract.</p><p><strong>Results: </strong>The highest total phenolic content (TPC) was observed in the water extract while highest TFC in ethanol/water extract. The most abundant compounds in the extracts were hyperoside (69041.06 mg kg^-1), isoquercitrin (46239.49 mg kg^-1), delphindin-3,5-diglucoside (42043.81 mg kg^-1), myricetin (21486.61 mg kg^-1), and kaempferol-3-glucoside (21199.76 mg kg^-1). Molecular dynamic (MD) simulations confirmed the structural stability and dynamic conformational integrity of these complexes over a period of 100 ns. In network pharmacology, A total of 657 unique target genes were screened: 52 associated with programmed cell death-1 (PD-1), 85 with vascular endothelial growth factor receptor-2 (VEGFR2), and 130 with fibroblast growth factor receptor-2 (FGFR2), identifying crucial gene interactions for these proteins. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted, revealing significant interactions and pathways such as the advanced glycation end products (AGE) and their receptors (RAGE) signaling pathway in diabetic complications and T- helper 17 (Th17) cell differentiation, among others. This elucidation of complex networks involving key genes like AKT Serine/Threonine Kinase 1 (AKT1), MYC proto-oncogene (MYC), tumor protein 53 (TP53), Interleukin 6 (IL6), and tumor necrosis factor (TNF) provides a promising foundation for the development of targeted therapies in the treatment of non-communicable diseases.</p><p><strong>Conclusion: </strong>These results show that <i>G. italicus</i> could be a natural source of potent antioxidants and enzyme inhibitors which need to be further explored for the development of biopharmaceuticals.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-21"},"PeriodicalIF":3.2,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142155034","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":"Mechanistic insights into the impact of WIN 55, 212-2, a synthetic cannabinoid, on adhesion molecules PECAM-1 and VE-cadherin in HeLa cells: implications on cancer processes.","authors":"Elizabeth Bejarano-Pérez, Rodolfo Sánchez-Zavaleta, Arnulfo Albores","doi":"10.1080/15376516.2024.2399132","DOIUrl":"10.1080/15376516.2024.2399132","url":null,"abstract":"<p><p>The endocannabinoid (eCB) system comprises endogenous ligands, cannabinoid receptors (CBRs), and their regulatory proteins; its alteration leads to many diseases including cancer. Thus, becomes a therapeutic target for synthetic cannabinoids aimed to control cancer cell proliferation, migration, adhesion, and invasion. However, little is known about adhesion molecules regulation through CBRs activation. The aim of this study was to evaluate the effects of a CB1/CB2 agonist, WIN-55, 212-2 (WIN), on the regulation of adhesion molecules platelet endothelial cell adhesion molecule-1 (PECAM-1) and vascular endothelial cadherin (VE-cadherin) in HeLa cells. CBRs expression was evaluated by immunofluorescence staining in HeLa cells and cell viability (thiazolyl blue tetrazolium bromide), cell adhesion (crystal violet), adhesion molecules expression and location (Western blot and immunofluorescence staining assays) were all assessed on cells treated with different WIN concentrations. Receptors CB1, CB2, and G-protein-coupled receptor 55 were expressed in HeLa cells. Additionally, biphasic effects were observed in their metabolic activity and adhesive properties: low WIN concentrations resulted in significant increases whereas, high ones decreased them compared to controls (<i>p</i> < 0.0001), demonstrating that WIN elicits opposite effects depending on the concentration and exposure time. PECAM-1 was detected in HeLa cell's cytoplasm, membrane, and perinuclear region, whereas VE-cadherin had a nuclear distribution. There were no significant differences in PECAM-1 and VE-cadherin expression and location, suggesting that WIN does not modulate these proteins. These findings support the potential use of WIN due to its anticancer properties without dysregulating adhesion molecules. WIN possible contribution to inhibit cancer progression should be further investigated.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-14"},"PeriodicalIF":3.2,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126743","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}