Chemical Research in Toxicology最新文献_第3页

Dr. Nathaniel Snyder, 2024 Young Investigator Award Recipient, American Chemical Society Division of Chemical Toxicology.

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-02-12 DOI: 10.1021/acs.chemrestox.4c00474

Don Pivithuru Liyanarachchi

引用次数: 0

Novel Organophosphate Ester Tris(2,4-di-tert-butylphenyl)phosphate Alters Lipid Metabolism: Insights from Lipidomic Analysis and mRNA Expression.

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-02-10 DOI: 10.1021/acs.chemrestox.4c00460

Pingping Kang, Qianyu Chen, Jia Wu, Qi Zhang, Doug Crump, Guanyong Su

{"title":"Novel Organophosphate Ester Tris(2,4-di-tert-butylphenyl)phosphate Alters Lipid Metabolism: Insights from Lipidomic Analysis and mRNA Expression.","authors":"Pingping Kang, Qianyu Chen, Jia Wu, Qi Zhang, Doug Crump, Guanyong Su","doi":"10.1021/acs.chemrestox.4c00460","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00460","url":null,"abstract":"Tris(2,4-di-tert-butylphenyl)phosphate (TDTBPP), a novel organophosphate ester (OPE), has been extensively detected in various environmental and biological samples; however, its potential biological effects remain unexplored. In this study, we investigated biotransformation characteristics, alteration of lipid metabolism, and mRNA expression in primary mouse hepatocytes (PMHs) following exposure to TDTBPP. After 36-h exposure in PMHs, TDTBPP exhibited a high stability potential with no statistically significant degradation trend. Subsequently, we analyzed the disruption of lipid homeostasis in PMHs following exposure to 0-4.5 μM TDTBPP. Lipidomic analysis indicated that TDTBPP disrupted lipid homeostasis in PMHs, and several lipid classes were dysregulated, in particular, glycerolipids and glycerophospholipids. Additionally, three lipids were proposed as potential lipid biomarkers of TDTBPP exposure, including triglycerides (TGs) and phosphatidylcholines (PCs). These observations were further supported by transcriptional changes, with significant alteration observed in genes associated with lipid uptake, de novo lipogenesis, β-oxidation of fatty acids, glycerolipid metabolism, and lipid export. Overall, these findings highlight the detrimental effects of TDTBPP on lipid homeostasis, providing important insights for health risk assessments of this abundant OPE in the environment.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389498","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

Metabolic Activation of Stiripentol Correlates with Cytotoxicity.

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-02-09 DOI: 10.1021/acs.chemrestox.4c00209

Ziying Jiang, Yang Wang, Guode Zhao, Xinyu Luo, Yan Shen, Weiwei Li, Ying Peng, Jiang Zheng

{"title":"Metabolic Activation of Stiripentol Correlates with Cytotoxicity.","authors":"Ziying Jiang, Yang Wang, Guode Zhao, Xinyu Luo, Yan Shen, Weiwei Li, Ying Peng, Jiang Zheng","doi":"10.1021/acs.chemrestox.4c00209","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00209","url":null,"abstract":"Stiripentol (SRP) is an antiepileptic agent utilized in managing seizures related to Dravet syndrome. Long-term safety studies have highlighted significant adverse effects in patients including drowsiness, reduced appetite, ataxia, and elevated levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The present study aimed at identifying the reactive metabolite of SRP and defining the potential correlation between its cytotoxicity and metabolic activation. Rat liver microsome incubation of SRP fortified with GSH as a trapping agent produced an α,β-unsaturated ketone metabolite (M1) and a related GSH conjugate (M2). Moreover, both the phase I metabolite and the GSH conjugate were detected in the bile of SRP-treated rats, indicating that both in vivo and in vitro metabolic activation of SRP took place. Notably, SRP exhibited significant cytotoxicity toward rat primary hepatocytes. Pretreatment with ketoconazole, a selective CYP3A enzyme inhibitor, mitigated the susceptibility of hepatocytes to SRP-induced cytotoxicity. These findings suggest that SRP may undergo metabolism to the α,β-unsaturated ketone metabolite, potentially contributing to the cytotoxic effects associated with SRP.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381221","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

Quantum Chemical Evaluation and QSAR Modeling of N-Nitrosamine Carcinogenicity

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-02-06 DOI: 10.1021/acs.chemrestox.4c0047610.1021/acs.chemrestox.4c00476

Sebastian Schieferdecker*, and , Esther Vock,

引用次数: 0

A High-Affinity and Selective DNA Aptamer for the N-Linked C8-Deoxyguanosine Adduct Produced by the Arylamine Carcinogen 4-Aminobiphenyl

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-02-05 DOI: 10.1021/acs.chemrestox.4c0049610.1021/acs.chemrestox.4c00496

Yijing Chen, Ryan E. Johnson, Richard A. Manderville* and Juewen Liu*,

{"title":"A High-Affinity and Selective DNA Aptamer for the N-Linked C8-Deoxyguanosine Adduct Produced by the Arylamine Carcinogen 4-Aminobiphenyl","authors":"Yijing Chen, Ryan E. Johnson, Richard A. Manderville* and Juewen Liu*, ","doi":"10.1021/acs.chemrestox.4c0049610.1021/acs.chemrestox.4c00496","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00496https://doi.org/10.1021/acs.chemrestox.4c00496","url":null,"abstract":"4-Aminobiphenyl (4-ABP) is a known human carcinogen that is implicated in the development of bladder cancers in smokers. The amine substituent undergoes bioactivation to generate nitrenium ions capable of covalently modifying DNA nucleobases. The primary adduct of 4-ABP, N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-ABP), is a bulky N-linked C8-dG adduct that serves as a biomarker for assessing the cancer risk associated with aromatic amine exposure. In this study, the capture-SELEX method was utilized to isolate DNA aptamers for dG-C8-ABP with high affinity and specificity. Using thioflavin T fluorescence spectroscopy and isothermal titration calorimetry, the parent aptamer PdG-1 has a Kd value below 100 nM and over 50-fold selectivity for dG-C8-ABP against competing analytes. A turn-on fluorescent sensor for dG-C8-ABP diagnostics, developed using a strand displacement assay, is also presented with a limit of detection of 68 nM. Our work represents the first selection of a DNA aptamer for a bulky DNA adduct produced by a known human carcinogen and sets the stage for the creation of ultrasensitive aptasensor platforms to meet the challenge of dG-C8-ABP detection in clinical settings.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"38 2","pages":"340–346 340–346"},"PeriodicalIF":3.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143418621","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

Inhibitory Effects of Alkaloids on OATP1B1 In Vitro and In Vivo: Prediction for Food/Herb–Drug Interactions and Hepatoprotective Effects Based on Structure–Activity Relationships

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-02-03 DOI: 10.1021/acs.chemrestox.4c0041810.1021/acs.chemrestox.4c00418

Yanhong Sun, Huixin Tan, Fenghe Wang, Jiahuan Hu, Xiaoyan Duan, Wanting Bai, Jinjin Wu, Jie Bai* and Jinping Hu*,

{"title":"Inhibitory Effects of Alkaloids on OATP1B1 In Vitro and In Vivo: Prediction for Food/Herb–Drug Interactions and Hepatoprotective Effects Based on Structure–Activity Relationships","authors":"Yanhong Sun, Huixin Tan, Fenghe Wang, Jiahuan Hu, Xiaoyan Duan, Wanting Bai, Jinjin Wu, Jie Bai* and Jinping Hu*, ","doi":"10.1021/acs.chemrestox.4c0041810.1021/acs.chemrestox.4c00418","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00418https://doi.org/10.1021/acs.chemrestox.4c00418","url":null,"abstract":"Alkaloids, a class of low-molecular-weight nitrogenous compounds, attract a great deal of interest because of their biological activities and therapeutic potential. Yet, surprisingly little is known about their interactions with drug transporters, especially Organic Anion Transporting Polypeptide 1B1 (OATP1B1), a liver-specific uptake transporter, which is closely associated with drug-induced liver injury (DILI). This study aims to investigate the inhibitory effects of 160 alkaloids on OATP1B1, assess the hepatoprotective effects against bosentan-induced liver injury, and elucidate the structure–activity relationships of alkaloids with OATP1B1. Four alkaloids, including dihydroberberine, deacetyltaxol, dihydrocapsaicin, and tetrahydropalmatine, significantly inhibited OATP1B1 transport activity in OATP1B1-HEK293 cells (>50%), which reduced the OATP1B1-mediated uptake of methotrexate and microcystin-LR, and consequently decreased their cell toxicity. In bosentan-induced liver injury models, 4 alkaloids reduced serum total bile acid (TBA) levels and liver concentration of bosentan to different degrees, especially deacetyltaxol, which exhibited the most potent hepatoprotective effect against bosentan. The pharmacophore model suggested that the critical pharmacophores of alkaloid inhibitors are hydrogen bond acceptors and hydrophobic groups. Our findings pave the way for predicting the potential risks of alkaloids-containing food/herb–drug interactions in humans and optimizing the alkaloid structure for alleviating OATP1B1-related DILI.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"38 2","pages":"281–295 281–295"},"PeriodicalIF":3.7,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143418660","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

Bisphenol A in Disposable Face Masks: A Novel Human Exposure Pathway and Impact on the Aquatic Environment

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-02-03 DOI: 10.1021/acs.chemrestox.4c0053510.1021/acs.chemrestox.4c00535

Hei-Tak Tse, Chun-Kit Au and Wan Chan*,

{"title":"Bisphenol A in Disposable Face Masks: A Novel Human Exposure Pathway and Impact on the Aquatic Environment","authors":"Hei-Tak Tse, Chun-Kit Au and Wan Chan*, ","doi":"10.1021/acs.chemrestox.4c0053510.1021/acs.chemrestox.4c00535","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00535https://doi.org/10.1021/acs.chemrestox.4c00535","url":null,"abstract":"We identified and quantified bisphenol A (BPA), a known estrogen-like endocrine disruptor, in disposable face mask samples collected in Hong Kong. Results revealed that BPA is a common contaminant in face masks, with concentrations reaching up to 2 μg/mask. Although polypropylene, the primary material used in mask production, is generally considered to be BPA-free, the contaminant likely originates from additives, such as flame retardants, added during manufacturing. With a dermal absorption coefficient of 0.59 for BPA, the data indicate that mask-borne BPA is readily absorbed by the skin. Notably, 8 of 85 samples could cause the user to exceed the tolerable daily BPA intake set by the European Food Safety Agency (0.0002 μg/kg body weight per day). Additionally, BPA dissolves completely in landfill leachate in less than 70 days, which poses previously unrecognized health and environmental hazards. Given the extensive use of face masks during the pandemic, their role as personal protective equipment for medical practitioners, and the fact that there are currently no regulations regarding BPA contents in masks, it is imperative to investigate the need for regulations in order to safeguard face mask users and the environment.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"38 2","pages":"347–352 347–352"},"PeriodicalIF":3.7,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.chemrestox.4c00535","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143418623","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

Cannabidiol Toxicity Driven by Hydroxyquinone Formation

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-01-29 DOI: 10.1021/acs.chemrestox.4c0044810.1021/acs.chemrestox.4c00448

Metzli I. Montero, Pravien S. Rajaram, Jose E. Zamora Alvarado, Kara E. McCloskey, Ryan D. Baxter* and Roberto C. Andresen Eguiluz*,

{"title":"Cannabidiol Toxicity Driven by Hydroxyquinone Formation","authors":"Metzli I. Montero, Pravien S. Rajaram, Jose E. Zamora Alvarado, Kara E. McCloskey, Ryan D. Baxter* and Roberto C. Andresen Eguiluz*, ","doi":"10.1021/acs.chemrestox.4c0044810.1021/acs.chemrestox.4c00448","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00448https://doi.org/10.1021/acs.chemrestox.4c00448","url":null,"abstract":"Oxidative byproducts of cannabidiol (CBD) are known to be cytotoxic. However, CBD susceptibility to oxidation and resulting toxicity dissolved in two common solvents, ethanol (EtOH) and dimethyl sulfoxide (DMSO), is seldom discussed. Furthermore, CBD products contain a wide range of concentrations, making it challenging to link general health risks associated with CBD cytotoxicity. Here, we report on the effect of CBD and CBD analogues dissolved in EtOH or DMSO at various concentrations. The cells used in these studies were human umbilical vascular endothelial cells (HUVECs). Our findings show significant CBD oxidation to cannabidiol-quinone (CBD-Q) and subsequent cytotoxicity, occurring at 10 μM concentration, regardless of the solution delivery vehicle. Moreover, a new analogue of CBD, cannabidiol-diacetate (CBD-DA), exhibits significantly more stability and reduced toxicity compared with CBD or CBD-Q, respectively. This knowledge is important for determining concentration-dependent health risks of complex cannabinoid mixtures and establishing legal limits.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"38 2","pages":"231–235 231–235"},"PeriodicalIF":3.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.chemrestox.4c00448","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143418719","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

Correction to “Berberine Inhibits KLF4 Promoter Methylation and Ferroptosis to Ameliorate Diabetic Nephropathy in Mice”

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-01-24 DOI: 10.1021/acs.chemrestox.5c0002210.1021/acs.chemrestox.5c00022

Shengyu Cai*, Huizheng Zhu, Lingling Chen, Congcong Yu, Liyuan Su, Kaihua Chen and Yousheng Li*,

引用次数: 0

Repurposing the Antihypertensive Agent Hydralazine As an Inhibitor of the Base Excision Repair Enzyme APE1. 降压药肼作为碱基切除修复酶APE1抑制剂的研究。

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-01-20 Epub Date: 2024-12-24 DOI: 10.1021/acs.chemrestox.4c00445

Tanhaul Islam, Venkatrao Nunna, Don Pivithuru Liyanarachchi, Douglas Melton, Calvin D Lewis, Kent S Gates

引用次数: 0