Journal of Applied Toxicology最新文献

Mechanistic Insights and Pharmacological Approaches for Nitrogen and Sulfur Mustards and Their Implications as Therapeutic Agents.

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2025-03-04 DOI: 10.1002/jat.4770

Madison Owens, Anita Thyagarajan, Jeffrey B Travers, Ravi P Sahu

{"title":"Mechanistic Insights and Pharmacological Approaches for Nitrogen and Sulfur Mustards and Their Implications as Therapeutic Agents.","authors":"Madison Owens, Anita Thyagarajan, Jeffrey B Travers, Ravi P Sahu","doi":"10.1002/jat.4770","DOIUrl":"https://doi.org/10.1002/jat.4770","url":null,"abstract":"Nitrogen and sulfur mustards, often acting as vesicants, have significant consequences for public health. Skin is a common site for exposure to these vesicants that can result in considerable morbidity and mortality. Given that the treatment options are limited, new insights into the mechanisms for the toxicity of these vesicants that can be translated into preventative/therapeutic strategies are desperately needed. Importantly, like most antineoplastic agents, including chemotherapy, the cytotoxic activity of vesicants such as nitrogen mustard (i.e., mustargen/mechlorethamine) and sulfur mustard is primarily mediated via their ability to act as alkylating agents. The current review highlights the underlying mechanisms, effects as well as approaches to mitigate sulfur and nitrogen mustard-induced effects, and their potential to be explored as therapeutic agents. Insights into the mediating roles and impacts of mustard agents could lead to future research and interventions that raise public health awareness to circumvent their adverse events and exploit desirable effects against proliferative diseases such as cancer.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542078","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}

引用次数: 0

Prolonged Low-Dose Chromium (VI) Exposure Induces Oxidative Stress, Apoptotic Genes and Epigenetic Modification of DNA Repair Genes in the Brain and Kidney of Swiss Albino Mice. 长期低剂量铬 (VI) 暴露会诱发瑞士白化小鼠大脑和肾脏中的氧化应激、凋亡基因和 DNA 修复基因的表观遗传学修饰。

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2025-02-27 DOI: 10.1002/jat.4769

Shehnaz Islam, Sunanda Mukherjee, Olivia Sarkar, Sreejata Kamila, Ansuman Chattopadhyay

{"title":"Prolonged Low-Dose Chromium (VI) Exposure Induces Oxidative Stress, Apoptotic Genes and Epigenetic Modification of DNA Repair Genes in the Brain and Kidney of Swiss Albino Mice.","authors":"Shehnaz Islam, Sunanda Mukherjee, Olivia Sarkar, Sreejata Kamila, Ansuman Chattopadhyay","doi":"10.1002/jat.4769","DOIUrl":"https://doi.org/10.1002/jat.4769","url":null,"abstract":"Hexavalent chromium (Cr (VI)) poses a major health risk due to its high solubility and cell permeability, often exceeding permitted drinking water limits globally. Research has highlighted a strong correlation between Cr (VI) exposure through drinking water and increased cancer rates, particularly in near chrome industries. Our previous research demonstrated that chronic low-dose Cr (VI) exposure (2, 5 and 10 ppm) via drinking water stimulated hepatotoxicity in Swiss albino mice. In this study, we investigated the effects of the same doses over 4 and 8 months on the brain and kidney tissues of Swiss albino mice. It was found that oxidative stress markers, including catalase activity, malondialdehyde (MDA) and reduced glutathione (GSH) levels, were significantly elevated in both the tissues post-treatment. Prolonged exposure to Cr (VI) led to DNA fragmentation and a reduced organo-somatic index in the affected tissues. Additionally, histoarchitectural alterations were observed in the brain and kidney. Apoptotic gene expression was significantly upregulated after 8 months of exposure, confirmed by immunohistochemical studies indicating apoptosis. DNA repair genes (Rad51, Mutyh, Ogg1, and Mlh1) and genes coding enzymes regulating epigenetics (Sirt1, Dnmt1, Kdm1a, and Ezh2) showed significantly varied expression patterns compared to control. Methylation-specific PCR revealed DNA hypermethylation as a factor in the transcriptional reduction of specific DNA repair genes in these tissues. This study denotes that long-term low-dose Cr (VI) exposure not only surges oxidative stress and changes histoarchitecture and gene expression but also results in epigenetic modifications via DNA hypermethylation, impacting organs like the brain and kidney.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523626","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}

引用次数: 0

Exposure to Polystyrene Nanoplastics Compromise Ovarian Reserve Function and Endometrial Decidualization in Early Pregnant Mice.

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2025-02-25 DOI: 10.1002/jat.4765

Qian-Feng Qiao, Li-Qing Wang, Qiong-Jun Xu, Xiao-Mei Wu, Qi-Duo Chen, Tao-Yu Sheng, Man-Xue Cui, Jing-Ai Li, Xiao-Qing Pang, Yong-Jiang Zhou

{"title":"Exposure to Polystyrene Nanoplastics Compromise Ovarian Reserve Function and Endometrial Decidualization in Early Pregnant Mice.","authors":"Qian-Feng Qiao, Li-Qing Wang, Qiong-Jun Xu, Xiao-Mei Wu, Qi-Duo Chen, Tao-Yu Sheng, Man-Xue Cui, Jing-Ai Li, Xiao-Qing Pang, Yong-Jiang Zhou","doi":"10.1002/jat.4765","DOIUrl":"https://doi.org/10.1002/jat.4765","url":null,"abstract":"In the environment, nanoplastics (NPs) have been shown to adversely impact reproductive health, yet research on their effects during early pregnancy is scarce. This study investigated the impact of NPs on endometrial decidualization in early pregnant mice and fertility. Female mice were administered polystyrene nanoplastics (PS-NPs) orally for 90 days before pregnancy. Our findings indicated that PS-NPs exposure decreased the live birth rate and neonatal crown-rump length. Decreased embryo implantation sites and uterine wet weight were observed post PS-NPs exposure. Histological examination revealed structural defects in the uteri of early pregnant mice and a significant reduction in follicular count across all stages in the PS-NPs-treated groups. Serum levels of estradiol (E2) and progesterone (P) were elevated, while follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were diminished post-exposure. Additionally, PS-NPs exposure upregulated the expression of the endometrial decidualization marker HOXA10 in uterine decidua. In conclusion, our results suggest that exposure to PS-NPs may disrupt endometrial decidualization during early pregnancy. This disruption is likely due to the perturbation of hormonal balance within the hypothalamic-pituitary-ovary including FSH, LH, E2, and P levels. These hormonal alterations may arrest follicular development, consequently leading to detrimental pregnancy outcomes and compromised neonatal birth conditions. Our study provided a new perspective on understanding the possible effects of microplastics on female fertility.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143501419","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}

引用次数: 0

Subchronic Toxicity Test of Transgenic Herbicide-Tolerant Soybean ZH10-6 in Rats.

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2025-02-23 DOI: 10.1002/jat.4766

Chao Han, JinPeng Zhao, Chen Chen, Yan Li, LiLi Shi

{"title":"Subchronic Toxicity Test of Transgenic Herbicide-Tolerant Soybean ZH10-6 in Rats.","authors":"Chao Han, JinPeng Zhao, Chen Chen, Yan Li, LiLi Shi","doi":"10.1002/jat.4766","DOIUrl":"https://doi.org/10.1002/jat.4766","url":null,"abstract":"The herbicide-tolerant soybean ZH10-6 was developed by modifying the Zhonghuang 10 (ZH10) variety with the G2-EPSPS and GAT genes, conferring resistance to glyphosate. This study aimed to assess the potential health effects of ZH10-6 in Sprague-Dawley rats through a 90-day subchronic toxicity test. Seven groups of rats (n = 10/sex/group) were fed a commercial AIN93G diet or diets containing 7.5%, 15%, or 30% ZH10-6 or ZH10 soybeans. General behavior, body weight, and food consumption were monitored weekly. At the end of the study, clinical pathology, including hematology, serum chemistry, urinalysis, and histopathology, were conducted. Throughout the study, all rats remained healthy and showed no abnormal clinical signs. Although some coagulation and serum biochemistry parameters showed statistical differences between groups, all values fell within the historical control ranges and were considered normal biological variability rather than treatment-related effects. The results indicate that ZH10-6 soybean consumption did not cause any adverse health effects in rats. These findings suggest that ZH10-6 is as safe as its nontransgenic parental variety, ZH10, with no evidence of toxicity after 90 days of exposure.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483022","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}

引用次数: 0

A Preliminary Quantitative Risk Assessment for Inhalation Exposure to Glutaraldehyde.

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2025-02-20 DOI: 10.1002/jat.4761

Sudha P Pandalai, David A Dankovic

{"title":"A Preliminary Quantitative Risk Assessment for Inhalation Exposure to Glutaraldehyde.","authors":"Sudha P Pandalai, David A Dankovic","doi":"10.1002/jat.4761","DOIUrl":"https://doi.org/10.1002/jat.4761","url":null,"abstract":"Glutaraldehyde (Chemical Abstracts Service [CAS] registry number 111-30-8) has various occupational uses and is associated with adverse health effects including respiratory tract irritation, asthma, and chronic obstructive pulmonary disease. A quantitative risk assessment was conducted to evaluate the likelihood of adverse health effects associated with differing levels of occupational inhalation exposure to glutaraldehyde. Dose-response models were fit to data from a 2-year glutaraldehyde inhalation exposure bioassay conducted by the National Toxicology Program. The benchmark concentration lower bound values of 32 and 44 parts per billion (ppb) were based on bioassay data for female rats and mice that developed squamous epithelium inflammation and respiratory epithelium squamous metaplasia, respectively. These values were used as a point of departure to determine exposure levels relevant to the occupational setting. Extrapolation from rodents to humans assumed a 40-h workweek and an 8-fold uncertainty factor to account for interspecies and interindividual variability. Adjusted benchmark lower bound concentrations of 3 and 4.1 ppb were calculated for inhalation exposure to glutaraldehyde using the endpoints observed in rat and mouse models. Due to the extrapolation parameters used in deriving this result, these findings have applicability for exposure to glutaraldehyde in the occupational setting.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467998","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}

引用次数: 0

Intestinal Bacterial Dysbiosis and Liver Fibrosis in Mice Through Gut-Liver Axis and NLRP3 Inflammatory Pathway Caused by Fine Particulate Matter.

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2025-02-20 DOI: 10.1002/jat.4767

Pengfei Fu, Mei Zhang, Lirong Bai, Shanshan Chen, Wenqi Chen, Zhiping Li, Jianwei Yue, Chuan Dong, Ruijin Li

{"title":"Intestinal Bacterial Dysbiosis and Liver Fibrosis in Mice Through Gut-Liver Axis and NLRP3 Inflammatory Pathway Caused by Fine Particulate Matter.","authors":"Pengfei Fu, Mei Zhang, Lirong Bai, Shanshan Chen, Wenqi Chen, Zhiping Li, Jianwei Yue, Chuan Dong, Ruijin Li","doi":"10.1002/jat.4767","DOIUrl":"https://doi.org/10.1002/jat.4767","url":null,"abstract":"Fine particulate matter (PM2.5) is associated with risks of liver diseases and intestinal bacterial dysbiosis, in which the gut-liver axis regulation mechanisms induced by PM2.5 exposure are still limited so far. In this study, after 12 weeks of exposure to atmospheric PM2.5 (64 μg/m3) and clean air in winter in Taiyuan, China, we collected liver and intestinal tissues and serum in male mice to perform toxicology experiments. The results showed that PM2.5 significantly exacerbated the pathological injury in the liver and intestine and liver fibrosis in mice, along with elevated levels of pro-inflammatory cytokines and lipopolysaccharide (LPS) levels in the serum. PM2.5 caused abnormal liver function and activated TLR4/NF-κB/NLRP3 pathway in mouse liver. PM2.5 also significantly inhibited the expression of intestinal mucosal tight junction proteins such as ZO-1 and occludin. Besides, from 16S rRNA gene sequencing results in intestinal and fecal samples, we found that PM2.5 decreased the diversity and abundance of intestinal bacteria, along with reducing Shannon, Chao1 and Ace indices and increasing Simpson indices. Principal component analysis (PCA) showed that mice's intestinal bacterial composition and β-diversity in the PM2.5-exposed group significantly differed from the control group. KEGG pathway analyzed key functional genes and metabolic pathways in important mouse bacterial communities in the PM2.5-exposed group. It suggested that PM2.5 exposure exacerbates liver fibrosis in mice via the NLRP3 pathway. PM2.5 caused intestinal mucosal injury, intestinal bacterial disorders and increased LPS levels, leading to the activation of inflammatory pathways, which can exacerbate liver fibrosis via the gut-liver axis.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468009","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}

引用次数: 0

The Mechanism of Bisphenol S-Induced Atherosclerosis Elucidated Based on Network Toxicology, Molecular Docking, and Machine Learning.

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2025-02-20 DOI: 10.1002/jat.4768

Bing Guo, Xuan He

{"title":"The Mechanism of Bisphenol S-Induced Atherosclerosis Elucidated Based on Network Toxicology, Molecular Docking, and Machine Learning.","authors":"Bing Guo, Xuan He","doi":"10.1002/jat.4768","DOIUrl":"https://doi.org/10.1002/jat.4768","url":null,"abstract":"The increasing prevalence of environmental pollutants has raised public concern about their potential role in diseases such as atherosclerosis (AS). Existing studies suggest that chemicals, including bisphenol S (BPS), may adversely affect cardiovascular health, but the specific mechanisms remain unclear. This study aims to elucidate the effects of BPS on AS and the underlying mechanisms. Through an extensive search of databases such as ChEMBL, STITCH, SwissTargetPrediction, SuperPred, SEA, and GEO, we identified 34 potential targets related to BPS-induced AS. A target network was constructed using the STRING platform and Cytoscape software. GO and KEGG functional enrichment analysis using the DAVID database revealed that BPS may promote the occurrence of AS by interfering with critical biological processes such as glutathione metabolism, nitrogen metabolism, and tyrosine metabolism. This was followed by the selection of 4 core targets-aminopeptidase n (ANPEP), alcohol dehydrogenase 5 (ADH5), lysosomal pro-x carboxypeptidase (PRCP), and microsomal glutathione s-transferase 1 (MGST1)-using five machine learning methods. These core targets play a pivotal role in BPS-induced AS. Furthermore, molecular docking confirmed the tight binding between BPS and these core targets. In conclusion, this study provides a theoretical framework for understanding the molecular mechanisms of BPS-induced AS and contributes scientific evidence for the development of prevention and treatment strategies for cardiovascular diseases triggered by BPS exposure.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468012","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}

引用次数: 0

Subchronic Inhalation of TiO₂ Nanoparticles Leads to Deposition in the Lung and Alterations in Erythrocyte Morphology in Mice.

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2025-02-11 DOI: 10.1002/jat.4759

Pavel Kulich, Soňa Marvanová, Radim Skoupý, Miša Škorič, Jan Vysloužil, Omar Šerý, Pavel Mikuška, Lukáš Alexa, Pavel Coufalík, Kamil Křůmal, Pavel Moravec, Zbyněk Večeřa, Miroslav Machala

{"title":"Subchronic Inhalation of TiO2 Nanoparticles Leads to Deposition in the Lung and Alterations in Erythrocyte Morphology in Mice.","authors":"Pavel Kulich, Soňa Marvanová, Radim Skoupý, Miša Škorič, Jan Vysloužil, Omar Šerý, Pavel Mikuška, Lukáš Alexa, Pavel Coufalík, Kamil Křůmal, Pavel Moravec, Zbyněk Večeřa, Miroslav Machala","doi":"10.1002/jat.4759","DOIUrl":"https://doi.org/10.1002/jat.4759","url":null,"abstract":"TiO2 nanoparticles (NPs) are extensively used in various applications, highlighting the importance of ongoing research into their effects. This work belongs among rare whole-body inhalation studies investigating the effects of TiO2 NPs on mice. Unlike previous studies, the concentration of TiO2 NPs in the inhalation chamber (130.8 μg/m3) was significantly lower. This 11-week study on mice confirmed in vivo the presence of TiO2 NPs in lung macrophages and type II pneumocytes including their intracellular localization by using the electron microscopy and the state-of-the-art methods detecting NPs' chemical identity/crystal structure, such as the energy-dispersed X-ray spectroscopy (EDX), cathodoluminescence (CL), and detailed diffraction pattern analysis using powder nanobeam diffraction (PNBD). For the first time in inhalation study in vivo, the alterations in erythrocyte morphology with evidence of echinocytes and stomatocytes, accompanied by iron accumulation in spleen, liver, and kidney, are reported following NP's exposure. Together with the histopathological evidence of hyperaemia in the spleen and kidney, and haemosiderin presence in the spleen, the finding of NPs containing iron might suggest the increased decomposition of damaged erythrocytes. The detection of TiO2 NPs on erythrocytes through CL analysis confirmed their potential systemic availability. On the contrary, TiO2 NPs were not confirmed in other organs (spleen, liver, and kidney); Ti was detected only in the kidney near the detection limit.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399399","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}

引用次数: 0

The Development of Yellow Mealworm (Tenebrio molitor) as a Cheap and Simple Model to Evaluate Acute Toxicity, Locomotor Activity Changes, and Metabolite Profile Alterations Induced by Nanoplastics of Different Sizes.

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2025-02-09 DOI: 10.1002/jat.4764

Miao Sun, Xiaomei Zhao, Sihuan Luo, Miao Jiang, Qing Liu, Yi Cao

{"title":"The Development of Yellow Mealworm (Tenebrio molitor) as a Cheap and Simple Model to Evaluate Acute Toxicity, Locomotor Activity Changes, and Metabolite Profile Alterations Induced by Nanoplastics of Different Sizes.","authors":"Miao Sun, Xiaomei Zhao, Sihuan Luo, Miao Jiang, Qing Liu, Yi Cao","doi":"10.1002/jat.4764","DOIUrl":"https://doi.org/10.1002/jat.4764","url":null,"abstract":"Due to the wide uses of plastic products, nanoplastics are ubiquitous contaminants in the environment. Hence, extensive studies used various models to evaluate the toxicity of nanoplastics. In the present study, we developed yellow mealworm (Tenebrio molitor) as an alternative model to investigate the acute toxicity of nanoplastics. Our results showed that microinjection with 500 mg/kg nanoplastics significantly increased death rate of yellow mealworms after 24 or 48 h, with 100 nm particles being more effective compared with 20 nm ones. Meanwhile, dose-dependent increase of death rate was observed in yellow mealworms after injection with 2-200 mg/kg 100 nm nanoplastics. Exposure to 2 mg/kg 100 nm but not 20 nm nanoplastics also led to hyperactivity of yellow mealworms. Both types of nanoplastics altered metabolite profiles, that 20 nm nanoplastics significantly up-regulated and down-regulated 9 and 12 metabolites, whereas 100 nm nanoplastics significantly up-regulated and down-regulated 16 and 25 metabolites, respectively. Enrichment analysis revealed that 100 nm but not 20 nm nanoplastics significantly affected alpha-linolenic acid metabolism (ko00592) and purine metabolism (ko00230). For the metabolites belonging to these pathways, 100 nm nanoplastics significantly up-regulated stearidonic acid but down-regulated guanine. Combined, these results revealed size-dependent effects of nanoplastics on acute toxicity, hyperactivity and metabolite profile changes in yellow mealworms. These results also indicated the potential uses of yellow mealworms as a cheap and simple model to evaluate the toxicity of nanoplastics.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382519","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}

引用次数: 0

Toll-Like Receptors in Pentachlorophenol- and Dibutyltin-Induced Production of Pro-Inflammatory Cytokines, Interleukin (IL)-1β, and IL-6, by Human Immune Cells.

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2025-02-06 DOI: 10.1002/jat.4762

Aleshia Seaton-Terry, Zinia Hunter, Meaghan Lewis, Sophia Fisher, Ellie Bray, Brian Townsend, Saleban Gabure, Latoya Daniel, Margaret Whalen

{"title":"Toll-Like Receptors in Pentachlorophenol- and Dibutyltin-Induced Production of Pro-Inflammatory Cytokines, Interleukin (IL)-1β, and IL-6, by Human Immune Cells.","authors":"Aleshia Seaton-Terry, Zinia Hunter, Meaghan Lewis, Sophia Fisher, Ellie Bray, Brian Townsend, Saleban Gabure, Latoya Daniel, Margaret Whalen","doi":"10.1002/jat.4762","DOIUrl":"https://doi.org/10.1002/jat.4762","url":null,"abstract":"Pentachlorophenol (PCP) and dibutyltin dichloride (DBT) contaminate the environment due to their diverse applications. PCP has been found from 0.26 to 5 μM in the serum of exposed individuals and at an average of 0.15 μM in the unexposed. DBT has been detected in human blood at levels up to 0.3 μM. Exposure to these contaminants is linked to pathological conditions including cancer. Interleukin-1 beta (IL-1β) and IL-6 are pro-inflammatory cytokines that when produced inappropriately can cause chronic inflammation, which is linked to pathologies including autoimmune diseases and cancer. PCP and DBT have been shown to increase the production of IL-1β and IL-6 by immune cells in a MAP kinase (MAPK) dependent process. Toll-like receptors (TLRs) activate the signaling pathways linked to MAPK that lead to production of these cytokines. This study demonstrates that PCP-induced production of IL-1β and IL-6 is dependent on TLR4 and TLR8, and independent of TLR1/2, TLR2, and TLR3. Additionally, DBT-induced IL-6 production depends on TLR1/2, whereas IL-1β production does not. Blocking the TLR-linked adapter protein, MyD88, lead to a loss of both PCP and DBT stimulation of IL-1β and IL-6. These findings indicate that both PCP and DBT interact with selected TLRs as part of their mechanisms of elevating the levels of critical pro-inflammatory cytokines, which may contribute to chronic inflammation and its related pathologies.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364794","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}

引用次数: 0