Chemical Research in Toxicology最新文献_第5页

Perfluorooctane Sulfonate (PFOS) and Related Compounds Induce Nuclear Receptor 4A1 (NR4A1)-Dependent Carcinogenesis. 全氟辛烷磺酸（PFOS）及相关化合物诱导核受体4A1 （NR4A1）依赖性癌变。

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-04-21 Epub Date: 2025-03-11 DOI: 10.1021/acs.chemrestox.4c00528

Amanuel Hailemariam, Srijana Upadhyay, Vinod Srivastava, Zahin Hafiz, Lei Zhang, Wai Ning Tiffany Tsui, Arafat Rahman Oany, Jaileen Rivera-Rodriguez, Robert S Chapkin, Nicole Riddell, Robert McCrindle, Alan McAlees, Stephen Safe

{"title":"Perfluorooctane Sulfonate (PFOS) and Related Compounds Induce Nuclear Receptor 4A1 (NR4A1)-Dependent Carcinogenesis.","authors":"Amanuel Hailemariam, Srijana Upadhyay, Vinod Srivastava, Zahin Hafiz, Lei Zhang, Wai Ning Tiffany Tsui, Arafat Rahman Oany, Jaileen Rivera-Rodriguez, Robert S Chapkin, Nicole Riddell, Robert McCrindle, Alan McAlees, Stephen Safe","doi":"10.1021/acs.chemrestox.4c00528","DOIUrl":"10.1021/acs.chemrestox.4c00528","url":null,"abstract":"Polyfluoroalkyl substances (PFAS) are widely used industrial compounds that have been identified as contaminants in almost every component of the global ecosystem, and in human studies, higher levels of PFAS have been correlated with increased incidence of multiple diseases. Based on the results of human and laboratory animal studies, we hypothesize that the orphan nuclear receptor 4A1 (NR4A1) may be a critical target for some PFAS such as the legacy linear polyfluorooctanesulfonate (PFOS) and other sulfonates. We show that PFOS and related compounds bound the ligand binding domain (LBD) of NR4A1 and induced the growth of several cancer cell lines and enhanced tumor growth in an athymic nude mouse model. Using NR4A1-responsive rhabdomyosarcoma Rh30 cells as a model, PFOS induced NR4A1-dependent cell proliferation and Rh30 cell migration and invasion. Moreover, in Rh30 cells, PFOS also induces several NR4A1-regulated genes including the PAX3-FOXO1 oncogene and downstream gene products, and in a chromatin immunoprecipitation assay, PFOS does not decrease NR4A1 binding to the promoter. These results demonstrate that PFOS is an NR4A1 ligand and enhances tumorigenesis through the activation of this receptor.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"705-716"},"PeriodicalIF":3.7,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

2-Ethylhexyl Diphenyl Phosphate Affects Steroidogenesis and Lipidome Profile in Human Adrenal (H295R) Cells. 2-乙基己基二苯基磷酸影响人肾上腺（H295R）细胞的甾体生成和脂质组谱

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-04-21 Epub Date: 2025-04-03 DOI: 10.1021/acs.chemrestox.5c00030

Chander K Negi, Darshak Gadara, Lola Bajard, Zdeněk Spáčil, Ludek Blaha

{"title":"2-Ethylhexyl Diphenyl Phosphate Affects Steroidogenesis and Lipidome Profile in Human Adrenal (H295R) Cells.","authors":"Chander K Negi, Darshak Gadara, Lola Bajard, Zdeněk Spáčil, Ludek Blaha","doi":"10.1021/acs.chemrestox.5c00030","DOIUrl":"10.1021/acs.chemrestox.5c00030","url":null,"abstract":"The ever-increasing use of chemicals and the rising incidence of adverse reproductive effects in the modern environment have become an emerging concern. Several studies have shown that environmental contaminants, such as organophosphate flame retardants (OPFRs), negatively impact reproductive health. To evaluate the potential endocrine-related adverse reproductive effects of widely used and priority-listed compound 2-Ethylhexyl diphenyl phosphate (EHDPP), we characterized its effects on adrenal steroidogenesis in human adrenocortical (H295R) cells. The cells were exposed to EHDPP (1 and 5 μM) for 48 h, and the production of hormones, including progesterone, androstenedione, testosterone, estradiol, cortisol, and aldosterone, was measured. In addition, LC-MS/MS-based lipidomics analysis was done to quantify intracellular lipid profiles, and transcriptional assays were performed to examine the expression of genes related to corticosteroidogenesis, lipid metabolism, and mitochondrial dynamics. Our findings indicate that EHDPP disrupts hormone regulation in vitro, as evidenced by increased estradiol, cortisol, and aldosterone secretion. The expression of key corticosteroidogenic genes (CYP11B2, CYP21A1, 3β-HSD2, and 17β-HSD1) was upregulated significantly upon EHDPP exposure. Intracellular lipidomics revealed EHDPP-mediated disruption, including reduced total cholesterol ester, sphingolipids, and increased phospholipids, triglyceride species, and saturated-monounsaturated lipids subspecies. These alterations were accompanied by decreased ACAT2 and SCD1 gene expression. Moreover, a shift in mitochondrial dynamics was indicated by increased MF1 expression and decreased FIS1 expression. These data suggest that EHDPP disrupts adrenal steroidogenesis and lipid homeostasis, emphasizing its potential endocrine-disrupting effects.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"733-744"},"PeriodicalIF":3.7,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DICTrank Is a Reliable Dataset for Cardiotoxicity Prediction Using Machine Learning Methods. DICTrank是使用机器学习方法进行心脏毒性预测的可靠数据集。

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-04-21 Epub Date: 2025-03-27 DOI: 10.1021/acs.chemrestox.4c00428

Yanyan Qu, Ting Li, Zhichao Liu, Weida Tong, Dongying Li

{"title":"DICTrank Is a Reliable Dataset for Cardiotoxicity Prediction Using Machine Learning Methods.","authors":"Yanyan Qu, Ting Li, Zhichao Liu, Weida Tong, Dongying Li","doi":"10.1021/acs.chemrestox.4c00428","DOIUrl":"10.1021/acs.chemrestox.4c00428","url":null,"abstract":"Drug-induced cardiotoxicity (DICT) is a significant challenge in drug development and public health. DICT can arise from various mechanisms; New Approach Methods (NAMs), including quantitative structure-activity relationships (QSARs), have been extensively developed to predict DICT based solely on individual mechanisms (e.g., hERG-related cardiotoxicity) due to the availability of datasets limited to specific mechanisms. While these efforts have significantly contributed to our understanding of cardiotoxicity, DICT assessment remains challenging, suggesting that approaches focusing on isolated mechanisms may not provide a comprehensive evaluation. To address this, we previously developed DICTrank, the largest dataset for assessing overall cardiotoxicity liability in humans based on FDA drug labels. In this study, we evaluated the utility of DICTrank for QSAR modeling using five machine learning methods─Logistic Regression (LR), K-Nearest Neighbors, Support Vector Machines, Random Forest (RF), and extreme gradient boosting (XGBoost)─which vary in algorithmic complexity and explainability. To reflect real-world scenarios, models were trained on drugs approved before and within 2005 to predict the DICT risk of those approved thereafter. While we observed no clear association between prediction performance and model complexity, LR and XGBoost achieved the best results with DICTrank. Additionally, our significant-feature analyses with RF and XGBoost models provided novel insights into DICT mechanisms, revealing that drug properties associated with descriptors such as \"structural and topological\", \"polarizability\", and \"electronegativity\" contributed significantly to DICT. Moreover, we found that model performance varied by therapeutic category, suggesting the need to tailor models accordingly. In conclusion, our study demonstrated the robustness and reliability of DICTrank for cardiotoxicity prediction in humans using machine learning methods.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"647-655"},"PeriodicalIF":3.7,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Nanoparticle-Mediated Embryotoxicity: Mechanisms of Chemical Toxicity and Implications for Biological Development. 纳米粒子介导的胚胎毒性：化学毒性机制及其对生物发育的影响。

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-04-21 Epub Date: 2025-03-19 DOI: 10.1021/acs.chemrestox.4c00472

Biswajeet Acharya, Amulyaratna Behera, Srikanta Moharana, Bhupendra G Prajapati, Suchismeeta Behera

{"title":"Nanoparticle-Mediated Embryotoxicity: Mechanisms of Chemical Toxicity and Implications for Biological Development.","authors":"Biswajeet Acharya, Amulyaratna Behera, Srikanta Moharana, Bhupendra G Prajapati, Suchismeeta Behera","doi":"10.1021/acs.chemrestox.4c00472","DOIUrl":"10.1021/acs.chemrestox.4c00472","url":null,"abstract":"Nanoparticles, defined by their nanoscale dimensions and unique physicochemical properties, are widely utilized in healthcare, electronics, environmental sciences, and consumer products. However, increasing evidence of their potential embryotoxic effects during pregnancy underscores the need for a molecular-level understanding of their interactions during embryonic development. Nanoparticles such as titanium dioxide, silver, cerium oxide, copper oxide, and quantum dots can cross the placental barrier and interfere with crucial developmental processes. At the molecular level, they disrupt signaling pathways like Wnt and Hedgehog, induce oxidative stress and inflammation, and cause genotoxic effects, all critical during sensitive phases, such as organogenesis. Furthermore, these nanoparticles interact directly with cellular components, including DNA, proteins, and lipids, impairing cellular function and viability. Innovative strategies to mitigate nanoparticle toxicity, such as surface modifications and incorporation of biocompatible coatings, are discussed as potential solutions to reduce adverse molecular interactions. Various laboratory animal models used to investigate nanoparticle-induced embryotoxicity are evaluated for their efficacy and limitations, providing insights into their applicability for understanding these effects. This Account examines the molecular mechanisms by which nanoparticles compromise embryonic development and emphasizes the importance of designing safer nanoparticles to minimize maternal-fetal exposure risks, particularly in biomedical applications.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"521-541"},"PeriodicalIF":3.7,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Gallstone Physicochemical Properties and Heavy Metal Concentrations Associated with Gallbladder Carcinogenesis in Assam, India. 印度阿萨姆邦胆结石理化性质和重金属浓度与胆囊癌的发生有关。

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-04-21 Epub Date: 2025-04-02 DOI: 10.1021/acs.chemrestox.4c00392

Cinmoyee Baruah, Sachin B Jorvekar, Anupam Sarma, Gayatri Gogoi, Nabanita Roy, Utpal Dutta, Subhash Khanna, Roshan M Borkar, Akshai Kumar, Pankaj Barah

{"title":"Gallstone Physicochemical Properties and Heavy Metal Concentrations Associated with Gallbladder Carcinogenesis in Assam, India.","authors":"Cinmoyee Baruah, Sachin B Jorvekar, Anupam Sarma, Gayatri Gogoi, Nabanita Roy, Utpal Dutta, Subhash Khanna, Roshan M Borkar, Akshai Kumar, Pankaj Barah","doi":"10.1021/acs.chemrestox.4c00392","DOIUrl":"10.1021/acs.chemrestox.4c00392","url":null,"abstract":"Gallbladder cancer (GBC) is an aggressive malignancy, with gallstone disease (GSD) recognized as the primary risk factor. Although the precise mechanism linking GSD to GBC remains unclear, evidence suggests that gallstone characteristics play a significant role. This study investigates the physicochemical characteristics of gallstones critical for GBC development. We analyzed 40 gallstone samples from 30 GSD and 10 GBC with GSD (GBCGS) patients using advanced spectroscopic and imaging techniques such as fourier transform infrared (FTIR), powder X-ray diffraction (PXRD), nuclear magnetic resonance (NMR), and scanning electron microscopy energy-dispersive X-ray (SEM-EDX)). Subsequently, elemental analysis of 10 gallstones each from GBCGS and GSD was conducted via inductively coupled plasma-mass spectrometry (ICP-MS). Gallstones from the GSD group were identified as cholesterol (70%), mixed (13.3%), pigment (6.7%), and calcium carbonate (10%), while the GBCGS group included only cholesterol (70%) and mixed (30%) types. Cholesterol was the dominant organic component in most gallstones, with the cholesterol and mixed types exhibiting highly crystalline phases characterized by a stacked plate-like microstructure, particularly prominent in the GBCGS group. Additionally, the GBCGS group revealed significantly higher concentrations of carcinogenic elements such as arsenic, chromium, mercury, iron, and lead (p < 0.05), suggesting their accumulation in the gallbladder and gallstones. Consequently, our findings highlight that the physicochemical properties of cholesterol-rich gallstones and exposure to carcinogenic elements play a key role in the pathogenesis of GBC in Assam. These results emphasize the need for further research into cholesterol dysregulation and its link to elemental toxicity.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"598-608"},"PeriodicalIF":3.7,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Systematic Investigation of CYP3A4 Using Side-by-Side Comparisons of Apo, Active Site, and Allosteric-Bound States. 利用载脂蛋白、活性位点和变构结合态的并排比较对CYP3A4进行系统研究。

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-04-21 Epub Date: 2025-03-19 DOI: 10.1021/acs.chemrestox.4c00387

Pranchal Shrivastava, Somnath Mondal, Shivani Thakur, Anu Manhas, Rukmankesh Mehra

{"title":"Systematic Investigation of CYP3A4 Using Side-by-Side Comparisons of Apo, Active Site, and Allosteric-Bound States.","authors":"Pranchal Shrivastava, Somnath Mondal, Shivani Thakur, Anu Manhas, Rukmankesh Mehra","doi":"10.1021/acs.chemrestox.4c00387","DOIUrl":"10.1021/acs.chemrestox.4c00387","url":null,"abstract":"Cytochrome P450 (CYP) 3A4 (CYP3A4) is a complex enzyme that metabolizes diverse substrates. It contains a large binding site accommodating diverse ligands, binding to active or allosteric sites. CYP3A4 does not always follow Michaelis-Menten kinetics. While Km reflects substrate affinity, it does not necessarily determine the enzyme's activity, though it is often considered indicative of substrate binding characteristics. The mechanism may be highly sophisticated and driven by multiple factors. This suggests that the ligand binding affinity alone may not explain the differential behavior of the enzyme conformational stability. Here, we analyzed sequence conserveness of 57 CYPs, followed by a detailed molecular dynamics simulation study (9 μs) on CYP3A4. We studied three CYP3A4 enzyme states (apo-state, active-site, and allosteric-site ligand-bound states) collected from the same experimental setup to reduce the systematic error. We found that the enzyme conformational stability followed a consistent trend of allosteric > active > apo states, which was inconsistent with the enzyme-ligand (active/allosteric) binding affinity and the ligand conformational stability. However, the heme group showed a significant protein affinity and stability pattern directly related to the enzyme stability, suggesting that the active/allosteric binding may work by influencing the heme-CYP3A4 binding affinity, and the allosteric ligand appeared to form the most stable enzyme state of the three studied states.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"583-597"},"PeriodicalIF":3.7,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Malondialdehyde Mediated Alpha-Synuclein Aggregation: A Plausible Etiology of Parkinson's Disease in Oxidative Stress. 丙二醛介导的α -突触核蛋白聚集：帕金森病在氧化应激中的一种可能的病因学。

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-04-21 Epub Date: 2025-04-07 DOI: 10.1021/acs.chemrestox.4c00348

Harsh Thakkar, Sayan Chatterjee, Arvind Verma, Naveen Chandrasekar, Amit Khairnar, Ravi P Shah

{"title":"Malondialdehyde Mediated Alpha-Synuclein Aggregation: A Plausible Etiology of Parkinson's Disease in Oxidative Stress.","authors":"Harsh Thakkar, Sayan Chatterjee, Arvind Verma, Naveen Chandrasekar, Amit Khairnar, Ravi P Shah","doi":"10.1021/acs.chemrestox.4c00348","DOIUrl":"10.1021/acs.chemrestox.4c00348","url":null,"abstract":"Malondialdehyde (MDA), a major reactive byproduct of lipid peroxidation, has been implicated in numerous pathological conditions as a result of altering the structure and function of crucial proteins. One such protein is α-synuclein (α-Syn), which plays a vital role in the pathogenesis of Parkinson's disease (PD). This study investigates the hypothesis that MDA causes structural alterations in α-Syn, promoting its aggregation and exacerbating its toxicological effects. In vivo experiments were conducted where MDA and MDA-modified α-Syn were injected to the brain of mice. Behavioral assessments were performed to evaluate motor function changes, while immunohistochemistry was employed to examine the extent of α-Syn aggregation in brain tissues. An extraction protocol was also developed exquisitely, enabling quantification of modified α-Syn from brain tissue. Moreover, 15Nitrogen-labeled α-Syn was employed to establish an absolute quantification method on nLC-HRMS/MS. Our findings demonstrate that MDA-induced modifications in α-Syn alter its structural properties and also significantly enhance its aggregation propensity, potentially contributing to the neurodegenerative processes observed in PD. The developed model displayed a nonreversible decline in motor function, neurodegeneration, and aggregation of proteins in the brain mimicking the PD conditions. This research provides valuable insights into the molecular mechanisms of PD, emphasizing the role of MDA-modified proteins in the etiology of PD.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"573-582"},"PeriodicalIF":3.7,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Nicotine Dosimetry in Evaluating Electronic Cigarettes Compared to Cigarette Smoking: Implications for Tobacco Regulatory Science. 评价电子烟与吸烟的尼古丁剂量学：对烟草管制科学的影响。

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-04-21 Epub Date: 2025-03-17 DOI: 10.1021/acs.chemrestox.4c00462

Neal L Benowitz, Hao-Yuan Yang, Peyton Jacob, Gideon St Helen

{"title":"Nicotine Dosimetry in Evaluating Electronic Cigarettes Compared to Cigarette Smoking: Implications for Tobacco Regulatory Science.","authors":"Neal L Benowitz, Hao-Yuan Yang, Peyton Jacob, Gideon St Helen","doi":"10.1021/acs.chemrestox.4c00462","DOIUrl":"10.1021/acs.chemrestox.4c00462","url":null,"abstract":"The delivery and systemic absorption of nicotine are important for assessing the potential safety and efficacy of novel inhaled nicotine delivery devices. We describe an experimental approach for examining systemic nicotine intake, looking at individual variability, comparing JUUL electronic cigarettes and cigarette smoking, and comparing standardized puffing and ad libitum use. Fourteen cigarette smokers who were infrequent e-cigarette users vaped JUUL or smoked cigarettes, both in a standardized session (ten 3.5 s puffs over 5 min) and in a 4 h ad libitum use session. Plasma nicotine concentrations were measured, and using sex and body weight-based population nicotine clearance predictions, systemic nicotine dose was estimated in each session. The pharmacokinetically (PK)-estimated nicotine dose in the standardized session averaged 0.55 mg (range 0.16-0.82) for JUUL and 1.15 mg (range 0.35-4.56) for cigarette smoking. The PK-estimated dose with ad libitum use averaged 4.1 mg (range 0.4-9.5) for JUUL and 5.0 mg (range 1.5-15) for smoking (average 3.4 cigarettes). Within individual correlations, comparing PK-estimated dose for JUUL use with standardized vs ad libitum session was weak (r = 0.45, NS) but was much stronger for cigarette smoking (r = 0.82, p < 0.001). Data from ad libitum use predicted that consumption of the liquid contained in a JUUL pod would correspond to smoking 15 cigarettes, which is similar to that observed in real world studies. We conclude that standardized vaping sessions do not predict usual nicotine self-administration behavior with ad libitum use. With ad libitum use, nicotine intake is much more similar to vaping and smoking and provides a much better predictor of product delivery in the real world. This approach is recommended for screening of novel inhaled nicotine devices and to aid FDA regulatory decision making.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"686-694"},"PeriodicalIF":3.7,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deconjugation of Polychlorinated Biphenyl Sulfates to Hydroxylated PCBs by Anaerobically Cultured Mouse and Human Gut Microbiota. 厌氧培养小鼠和人肠道微生物群对羟基多氯联苯硫酸盐的解偶联作用。

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-04-21 Epub Date: 2025-03-25 DOI: 10.1021/acs.chemrestox.5c00016

Xueshu Li, Joe J Lim, Cayen Rong, Hans-Joachim Lehmler, Julia Yue Cui

引用次数: 0

Diallyl Disulfide Reduces Ethyl Carbamate-Induced Cytotoxicity and Apoptosis in Intestinal and Hepatic Cells. 二烯丙基二硫醚降低氨基甲酸乙酯诱导的肠和肝细胞的细胞毒性和凋亡。

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-04-21 Epub Date: 2025-03-27 DOI: 10.1021/acs.chemrestox.4c00439

Caroline Andolfato Sanchez, Estefani Maria Treviso, Cecília Cristina de Souza Rocha, Lusânia Maria Greggi Antunes

{"title":"Diallyl Disulfide Reduces Ethyl Carbamate-Induced Cytotoxicity and Apoptosis in Intestinal and Hepatic Cells.","authors":"Caroline Andolfato Sanchez, Estefani Maria Treviso, Cecília Cristina de Souza Rocha, Lusânia Maria Greggi Antunes","doi":"10.1021/acs.chemrestox.4c00439","DOIUrl":"10.1021/acs.chemrestox.4c00439","url":null,"abstract":"Epidemiological studies indicate that lifestyle and dietary habits are associated with an increasing cancer incidence. Consuming fermented foods and alcoholic beverages and smoking can expose humans to ethyl carbamate (EC), a probable human carcinogen classified as group 2A by the International Agency for Research on Cancer (IARC). Increasing the intake of bioactive compounds can reduce EC-induced toxicity. Diallyl disulfide (DADS), found in garlic, may protect against damage induced by chemical agents and natural compounds. Here, the potential protective effect of DADS against EC was investigated by evaluating EC-induced cytotoxicity, DNA damage, apoptosis, and reactive oxygen species production in colorectal adenocarcinoma (Caco-2) and hepatocarcinoma (HepG2) cells. To this end, resazurin, comet, and annexin V-FITC staining assays and CM-H2DCFDA markers were used to evaluate the effect on Caco-2 and HepG2 cells of protocols combining DADS (10-120 μM) and EC (80 mM). The protocols were as follows: (i) cells pretreated with DADS for 2 h and exposed to EC for 24 h; (ii) cells pretreated with DADS for 24 h and exposed to EC for 24 h; (iii) cells simultaneously exposed to DADS and EC for 24 h; (iv) cells exposed to EC for 24 h and treated with DADS for 2 h. EC induced cytotoxicity and apoptosis in Caco-2 and HepG2 cells and oxidative damage in Caco-2 cells. Combined exposure to DADS and EC for 24 h decreased EC-mediated cytotoxicity and apoptosis in both Caco-2 and HepG2 cells. These findings encourage further studies on the mechanisms of action of the combined DADS and EC.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"623-634"},"PeriodicalIF":3.7,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0