Current Research in Toxicology最新文献

{"title":"Effects of mineral fibres in an in vitro placental syncytiotrophoblast model","authors":"Giovanni Tossetta ,&nbsp;Sonia Fantone ,&nbsp;Antonio Domenico Procopio ,&nbsp;Armanda Pugnaloni ,&nbsp;Alessandro Francesco Gualtieri ,&nbsp;Daniela Marzioni","doi":"10.1016/j.crtox.2025.100231","DOIUrl":"10.1016/j.crtox.2025.100231","url":null,"abstract":"<div><div>It is known that mineral fibres can be found in placental tissues, but their effect is not known on these tissues. BeWo in vitro model of syncytiotrophoblast, the outer layer of maternal-foetal barrier, is necessary to understand if mineral fibres can alter placental cell turnover and consequently to influence the outcome of pregnancy. We performed in vitro experiments using chrysotile UICC (UICC), chrysotile Valmalenco (VM) and erionite (ERI) to investigate the potential cytotoxic effects of these mineral fibres on BeWo cells. We demonstrated that all fibres are toxic while only UICC fibres caused a DNA damage that the cells were not able to repair through RAD51 activity. In addition, we demonstrated that DNA replication is not altered while cyclin D1 showed a significant decrease in VM and UICC suggesting that the cell cycle is altered in G1 phase. Moreover, UICC increased active form of caspase 3 demonstrating that apoptosis can be induced in BeWo cells. We suggest that although morphological changes are not visible in BeWo cells treated with these mineral fibres, DNA damage can lead to altered placenta physiology that can be seen late when the damage at the foetal tissues has already occurred.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100231"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the endocrine disrupting potential of Di-isononyl phthalate","authors":"I.A. Lea ,&nbsp;A.N. Buerger ,&nbsp;D. Feifarek ,&nbsp;A. Mihalchik ,&nbsp;M.M. Heintz ,&nbsp;L.C. Haws ,&nbsp;H. Nyambego ,&nbsp;K. Goyak ,&nbsp;C. Palermo ,&nbsp;S.J. Borghoff","doi":"10.1016/j.crtox.2025.100220","DOIUrl":"10.1016/j.crtox.2025.100220","url":null,"abstract":"<div><div>Low molecular weight <em>ortho</em>-phthalate compounds have been implicated in disruption of androgen pathways when exposure occurs during the masculinization programming window. Di-isononyl phthalate (DINP) is a high molecular weight phthalate and a high production volume chemical. To understand the potential for DINP and its metabolites to disrupt endocrine pathways, a weight of evidence assessment was conducted according to the European Chemicals Agency (ECHA)/ European Food Safety Authority (EFSA) Endocrine Disruptor Guidance (2018). Toxicological data related to estrogen (E), androgen (A), thyroid (T), or steroidogenesis (S) pathways was assessed. Literature searches returned 110 articles from which data were extracted and assessed in conjunction with 105 high-throughput assays. An <em>in-silico</em> assessment of the EATS activity for DINP metabolites also was conducted. Based on the available evidence, DINP did not elicit thyroid- or estrogen-related apical outcomes <em>in vivo.</em> There were no studies evaluating thyroid hormone levels <em>in vivo</em> which, according to the ECHA/EFSA guidance, constitutes a data gap and prevents a conclusion being drawn on the T-pathway. The E, A, and S-pathways were sufficiently assessed to conclude on the endocrine disrupting potential of DINP. Based on the lack of apical outcomes, DINP did not disrupt the E-pathway. For the A and S-pathways, there was limited evidence to support adverse apical outcomes, so a mode of action assessment using a structured adverse outcome pathway (AOP) framework was performed. No biologically plausible link could be established between the key events in the hypothesized AOP that lead to adverse outcomes. Further, no dose or temporal concordance for A- and S-mediated findings were identified. Therefore, DINP does not meet the ECHA/EFSA criteria to be considered an endocrine disruptor.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100220"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A computational dynamic systems model for in silico prediction of neural tube closure defects","authors":"Job H. Berkhout ,&nbsp;James A. Glazier ,&nbsp;Aldert H. Piersma ,&nbsp;Julio M. Belmonte ,&nbsp;Juliette Legler ,&nbsp;Richard M. Spencer ,&nbsp;Thomas B. Knudsen ,&nbsp;Harm J. Heusinkveld","doi":"10.1016/j.crtox.2024.100210","DOIUrl":"10.1016/j.crtox.2024.100210","url":null,"abstract":"<div><div>Neural tube closure is a critical morphogenetic event during early vertebrate development. This complex process is susceptible to perturbation by genetic errors and chemical disruption, which can induce severe neural tube defects (NTDs) such as spina bifida. We built a computational agent-based model (ABM) of neural tube development based on the known biology of morphogenetic signals and cellular biomechanics underlying neural fold elevation, bending and fusion. The computer model functionalizes cell signals and responses to render a dynamic representation of neural tube closure. Perturbations in the control network can then be introduced synthetically or from biological data to yield quantitative simulation and probabilistic prediction of NTDs by incidence and degree of defect. Translational applications of the model include mechanistic understanding of how singular or combinatorial alterations in gene-environmental interactions and animal-free assessment of developmental toxicity for an important human birth defect (spina bifida) and potentially other neurological problems linked to development of the brain and spinal cord.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100210"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of a hypothesized Sertoli cell-based adverse outcome pathway for effects of diisononyl phthalate on the developing testis","authors":"J.M. Rogers ,&nbsp;A.N. Buerger ,&nbsp;M.M. Heintz ,&nbsp;C.M. Palermo ,&nbsp;L.C. Haws ,&nbsp;I.A. Lea","doi":"10.1016/j.crtox.2025.100219","DOIUrl":"10.1016/j.crtox.2025.100219","url":null,"abstract":"<div><div>Exposure of pregnant rats to some phthalates during the masculinization programming window (MPW) can lower fetal testis testosterone production and adversely affect development of the fetal male reproductive tract. Some of the effects in rats are androgen-dependent, while others also occur in mice without lower testosterone production. An adverse outcome pathway (AOP) network has been proposed for these developmental effects that includes both androgen-dependent and androgen-independent pathways, the latter of which includes a short list of putative molecular initiating events (MIEs) including peroxisome proliferator activated receptor (PPAR) activation, and effects on Sertoli cells in the developing testes as early key events (KEs) (PMID 34314370). Data from peer-reviewed literature, publicly cited toxicology reports, and EPA’s Toxicity Forecaster (ToxCast) were evaluated in the context of this hypothesized Sertoli cell-based AOP and exposure to diisononyl phthalate (DINP). Each of the fifteen identified studies underwent a risk of bias (RoB) assessment, which revealed a high risk of bias for all but one study endpoint. <em>In vitro</em> evidence in kidney, liver, and fibroblast-like cell lines indicates that the DINP metabolites mono-isononyl phthalate (MINP) and mono-hydroxyisononyl phthalate (MHINP) activate PPARα/γ and that mouse PPARα/γ are more sensitive than human PPARα/γ. However, DINP did not activate PPARα-related genes in rat fetal testes at high maternal dosages (PMID 22112501), and it remains unknown whether PPARs are expressed in fetal Sertoli cells. Overall, there is insufficient evidence to evaluate whether PPAR activation in the developing male reproductive tract is causally linked to the KEs in the hypothesized AOP. Regarding the KEs, no <em>in vivo</em> studies were identified that examined the effects of DINP on Sertoli cell proliferation or cytoskeleton; a single <em>in vitro</em> study found no effect of DINP on Sertoli cell proliferation. There was limited and conflicting evidence for the effects of DINP on tubulogenesis, but strong <em>in vivo</em> evidence for increased multinucleated germ (MNG) cells. No evidence was found concerning germ cell apoptosis. For the adverse outcomes (AOs), there was limited <em>in vivo</em> evidence for testicular dysgenesis following altered tubulogenesis, and impaired spermatogenesis following increased MNGs. There was strong evidence against reduced fertility, but this is not a sensitive endpoint in rats given their robust sperm production and excess capacity. In conclusion, following <em>in utero</em> DINP exposure, while PPAR activation (MIE) is plausible, linkage to effects on Sertoli cells and downstream AOPs is lacking. The sparse evidence currently available is insufficient to support the applicability of the hypothesized Sertoli cell-based AOP to DINP.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100219"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting seizure liability of small molecules using an in vitro multi-electrode array based assay coupled with modeling of brain disposition","authors":"David G. Belair ,&nbsp;Rebecca Kohnken ,&nbsp;Rebecca L. McCloud ,&nbsp;Stephanie Sandoval ,&nbsp;Jonathon Green ,&nbsp;Wayne R. Buck ,&nbsp;James S. Polakowski","doi":"10.1016/j.crtox.2025.100236","DOIUrl":"10.1016/j.crtox.2025.100236","url":null,"abstract":"<div><div>Unintended central nervous system (CNS) effects of small molecule drugs can lead to costly attrition during drug development. CNS liability can be assessed with biochemical assays, as part of routine nonclinical toxicology studies, or via a battery of rodent CNS tests. Alternative in vitro methods have been developed for assessing CNS liability of small molecule drugs though their use in drug development has lagged relative to other organ systems of interest including cardiac, hepatic, and gastrointestinal. In the present study, 13 commercially available small molecule drugs and 15 experimental AbbVie compounds were evaluated in an in vitro seizure assay consisting of human-induced pluripotent stem cell (hiPSC)-derived glutamatergic neurons cultured on a multi-electrode array (MEA). Across all 28 compounds, the in vitro seizure assay exhibited 58% sensitivity and 78% specificity. A mathematical model of brain penetrance was used to predict brain exposures in cynomolgus monkey and improved the concordance of the in vitro seizure assay with in vivo seizure liability, highlighting that the in vitro assay together with CNS exposure prediction could serve as a useful tool for characterizing seizure liability of a small molecule drug candidate.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100236"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143900388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatics study and cytotoxicity of several curcumin analogues in ovarian cancer","authors":"Retno Murwanti ,&nbsp;Ritmaleni ,&nbsp;Navista Sri Octa Ujiantari ,&nbsp;I Made Rhamandana Putra ,&nbsp;Aliffian Farhan Wahyudi ,&nbsp;Vigha Ilmanafi Arifka","doi":"10.1016/j.crtox.2025.100230","DOIUrl":"10.1016/j.crtox.2025.100230","url":null,"abstract":"<div><div>Ovarian cancer ranks as Indonesia’s third-leading cause of cancer-related death, emphasising the need for innovative treatments. This study combined bioinformatics, molecular docking, and experimental assays to tackle this challenge. We identified 166 ovarian cancer-related genes, with MYC standing out as a key target. Analysis of MYC mutations revealed prevalent alterations, though no significant survival differences were observed in patients with or without the mutations. Molecular docking pinpointed compound B155 as a promising MYC inhibitor. A preliminary cytotoxicity assay revealed compound B155′s notable activity, with an 87.19 % inhibition of cell viability at 50 μM. Most of the other curcumin analogues only caused more than 50 % inhibition at the same concentration. This result suggests alternative mechanisms of action, possibly antioxidant effects, warranting further exploration. In summary, this study unveiled MYC as a prime target for ovarian cancer treatment, with curcumin analogues like B155 showing potential. Nonetheless, the complex factors affecting cytotoxicity underscore the need for deeper investigation into these compounds’ mechanisms in ovarian cancer cells.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100230"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential effect of targeting cisplatin-induced nitrative stress using MnTBAP in auditory and cancer cells","authors":"Shomaila Mehmood,&nbsp;Pankaj Bhatia,&nbsp;Nicole Doyon-Reale,&nbsp;Samson Jamesdaniel","doi":"10.1016/j.crtox.2025.100241","DOIUrl":"10.1016/j.crtox.2025.100241","url":null,"abstract":"<div><div>Ototoxicity is a major dose-limiting side effect of cisplatin, a highly effective anti-cancer drug used to treat many solid tumors. Oxidative stress plays a central role in mediating cisplatin-induced ototoxicity. However, broad-spectrum antioxidants that prevent ototoxicity compromise the anti-cancer activity of cisplatin. Therefore, there is a need to identify novel interventional targets/compounds for otoprotection. Recent reports indicated that cisplatin-induced nitration of cochlear proteins is a critical factor in causing ototoxicity, and inhibition of cochlear nitrative stress mitigated cisplatin-induced ototoxicity. The use of peroxynitrite decomposition catalysts that selectively target nitrative stress appears to be an attractive strategy for mitigating the ototoxic effects of cisplatin because they do not scavenge free radicals. We hypothesized that cotreatment with selective inhibitors of nitrative stress prevents cisplatin-induced ototoxicity without compromising the anti-cancer effects. Here, we test this hypothesis by investigating the effect of MnTBAP cotreatment on cell viability, nitrative stress, DNA damage, and cell migration in cisplatin-treated organ of Corti as well as cancer cells. Our results indicate that cisplatin treatment decreases cell viability in both auditory and cancer cells, while cotreatment with MnTBAP mitigates cisplatin-induced cytotoxicity in the auditory cells but not in the cancer cells. Collectively, the findings of this study suggest that selective targeting of cisplatin-induced nitrative stress is a promising strategy for mitigating the ototoxic effects of cisplatin because it does not compromise the anti-cancer effects.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100241"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144106152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a workflow for in vitro on– and off-target cytotoxicity assessment of CAR T cell therapies to support first-in-human clinical trials: An orthogonal approach using human induced pluripotent stem cell-derived cells as a surrogate for normal vital organ systems","authors":"Shari Price ,&nbsp;Krista G. Zindel ,&nbsp;Joshua K. Overcash ,&nbsp;Elizabeth Glaze ,&nbsp;Sandy Eldridge","doi":"10.1016/j.crtox.2025.100243","DOIUrl":"10.1016/j.crtox.2025.100243","url":null,"abstract":"<div><div>Chimeric antigen receptor (CAR) T cell therapy has revolutionized cancer therapy and is showing promise for other non-cancer disease indications. CAR T cells are directed to a target antigen that is overexpressed by tumor cells. On-target toxicity can arise if the targeted protein is also expressed in normal cell populations. Additionally, off-target toxicity may occur if the CAR T cell recognizes or cross-reacts with a non-target protein thereby activating the T cells leading to subsequent adverse sequela. Given the nature of this biological class as a human cellular product, standard safety assessments in animals are largely not appropriate as the drug product is derived from human cells and the associated CAR often lacks reactivity with the animal homolog of the target protein. Undesired targeting of healthy/normal tissue that express the intended target antigen (on-target/off-tumor), as well as unintended targeting of other antigens expressed on healthy/normal tissue is a safety concern that may be explored using human induced pluripotent stem cell (hiPSC)-derived test systems as surrogates for various normal cell types. The panel of hiPSC-derived cells is intended to broadly represent different human cell types from vital organs that can be targets for severe adverse events. Herein the development of an orthogonal approach to an in vitro co-culture assay used to assess unintended CAR T cell cytotoxicity in normal cells is described. Experimental considerations including assay and cell model qualification are presented, and an orthogonal workflow described. Finally, an illustrative case of experimental CD33 CAR T cells co-cultured with a select panel of hiPSC-derived normal cells serves as a springboard for other CAR T cell developers to consider in their nonclinical safety programs.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100243"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144177633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomic profiling reveals systemic metabolic disruptions induced by combined exposure to particulate matter and ozone","authors":"Yue Ge ,&nbsp;Maliha S. Nash ,&nbsp;Aimen K. Farraj","doi":"10.1016/j.crtox.2025.100216","DOIUrl":"10.1016/j.crtox.2025.100216","url":null,"abstract":"<div><div>Air pollution exposure, especially particulate matter (PM) and ozone (O₃), poses significant health risks, but the systemic metabolic consequences of combined exposures to PM and O₃, remain poorly understood. This study investigated systemic metabolic changes in male spontaneously hypertensive (SH) rats following inhalation exposure to concentrated ambient particles (CAPs) (PM2.5, 150 μg/m³), ozone (O₃) (0.2 ppm), and their combination. Rats were exposed for 4 h, and serum samples were collected 1-hour post-exposure. Using targeted metabolomics, we identified significant alterations in metabolites involved in lipid metabolism (phosphatidylcholines), energy metabolism (acylcarnitine C3), and oxidative stress (glutamine). Notably, the combination exposure induced distinct metabolic changes, including increased acylcarnitine C3 levels, suggesting heightened mitochondrial dysfunction. Principal component analysis revealed overlapping profiles between CAPs and controls, indicating a subtler impact of CAPs compared to ozone or combined exposure. These systemic metabolic alterations are aligned with our previously published proteomics findings in cardiac tissues from the same rats, which showed elevated inflammatory markers (e.g., IL-6, TNF-α) and mitochondrial dysfunction. In conclusion, this study provides new insights into the systemic metabolic effects of air pollutant exposure, identifies novel metabolic targets of pollutant-induced toxicity, highlights the complex interactions resulting from combined exposure to multiple pollutants, and underscores the importance of assessing the combined effects of multiple pollutants in air pollution risk assessments.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100216"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143161099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exacerbation of polyethylene microplastics in animal models of DSS-induced colitis through damage to intestinal epithelial cell conjunctions","authors":"Minkyoung Sung ,&nbsp;Yeon-Ji Lee ,&nbsp;Soo-Eun Sung ,&nbsp;Kyung-Ku Kang ,&nbsp;Jae Woo Park ,&nbsp;Yujeong Lee ,&nbsp;Dongmin Kim ,&nbsp;Sunjong Lee ,&nbsp;Joo-Hee Choi ,&nbsp;Sijoon Lee","doi":"10.1016/j.crtox.2025.100217","DOIUrl":"10.1016/j.crtox.2025.100217","url":null,"abstract":"<div><div>Microplastics are pollutants that occur in various environments and habitats. Inflammatory bowel disease (IBD) is a chronic inflammatory disease accompanied with diarrhea, and the number of patients has increased worldwide. In this study, manufactured fragmented polyethylene-microplastics in the size range of 10–30 ㎛, were oxidized by exposure to ultraviolet light, and then administered to a dextran sodium sulfate-induced colitis mouse model to observe the effects of polyethylene-microplastics on IBD. In the microplastics-treated groups, an increase in disease activity index score, histopathological score, and a decrease in the areas of goblet cells were observed. In addition, the tight junction proteins, ZO-1 and Occludin, were significantly decreased, whereas MPO was significantly increased. Interestingly, E-cadherin, which is an adheren junction, was also decreased, presumably because of the physical effects of microplastics. The results suggest that polyethylene-microplastics worsen IBD and microplastics can affect not only tight junctions, but also adheren junctions.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100217"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143161100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}