Chemical Research in Toxicology最新文献

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Nicotinamide riboside Induced Energy Stress and Metabolic Reprogramming in BEAS-2B Cells. 烟酰胺核苷诱导 BEAS-2B 细胞的能量应激和代谢重编程。
IF 3.7 3区 医学
Chemical Research in Toxicology Pub Date : 2024-07-11 DOI: 10.1021/acs.chemrestox.3c00312
Everson Willian Fialho Cordeiro, Elisabete Leide Marzola, Ricardo Soei Maekawa, Matheus Relvas Dos Santos, Lucas Gade Assunção, Mariana Pereira Massafera, Joseana de Oliveira, Thainá Gomes Cury Batista, Maria Cármen Oliveira Pinho de Sales, Silvya Stuchi Maria-Engler, Paolo Di Mascio, Marisa Helena Gennari de Medeiros, Graziella Eliza Ronsein, Ana Paula de Melo Loureiro
{"title":"Nicotinamide riboside Induced Energy Stress and Metabolic Reprogramming in BEAS-2B Cells.","authors":"Everson Willian Fialho Cordeiro, Elisabete Leide Marzola, Ricardo Soei Maekawa, Matheus Relvas Dos Santos, Lucas Gade Assunção, Mariana Pereira Massafera, Joseana de Oliveira, Thainá Gomes Cury Batista, Maria Cármen Oliveira Pinho de Sales, Silvya Stuchi Maria-Engler, Paolo Di Mascio, Marisa Helena Gennari de Medeiros, Graziella Eliza Ronsein, Ana Paula de Melo Loureiro","doi":"10.1021/acs.chemrestox.3c00312","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.3c00312","url":null,"abstract":"<p><p>Nicotinamide riboside (NR), a NAD<sup>+</sup> precursor, has received attention due to several health benefits it has induced in experimental models. Studies in cultured cells, animals, and humans consistently show increased NAD<sup>+</sup> availability after NR supplementation, which is considered the only mode of NR action that leads to health benefits. In the present study, we show that a persistently low NR concentration (1 μM) in the growth medium of BEAS-2B human cells, grown in a monolayer, induces energy stress, which precedes a cellular NAD<sup>+</sup> increase after 192 h. NR concentrations greater than 1 μM under the specified conditions were cytotoxic in the 2D cell culture model, while all concentrations tested in the 3D cell culture model (BEAS-2B cell spheroids exposed to 1, 5, 10, and 50 μM NR) induced apoptosis. Shotgun proteomics revealed that NR modulated the abundance of proteins, agreeing with the observed effects on cellular energy metabolism and cell growth or survival. Energy stress may activate pathways that lead to health benefits such as cancer prevention. Accordingly, the premalignant 1198 cell line was more sensitive to NR cytotoxicity than the phenotypically normal parent BEAS-2B cell line. The role of a mild energy stress induced by low concentrations of NR in its beneficial effects deserves further investigation. On the other hand, strategies to increase the bioavailability of NR require attention to toxic effects that may arise.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141588916","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
Improved Detection of Drug-Induced Liver Injury by Integrating Predicted In Vivo and In Vitro Data. 通过整合体内和体外预测数据改进药物诱发肝损伤的检测。
IF 3.7 3区 医学
Chemical Research in Toxicology Pub Date : 2024-07-09 DOI: 10.1021/acs.chemrestox.4c00015
Srijit Seal, Dominic Williams, Layla Hosseini-Gerami, Manas Mahale, Anne E Carpenter, Ola Spjuth, Andreas Bender
{"title":"Improved Detection of Drug-Induced Liver Injury by Integrating Predicted <i>In Vivo</i> and <i>In Vitro</i> Data.","authors":"Srijit Seal, Dominic Williams, Layla Hosseini-Gerami, Manas Mahale, Anne E Carpenter, Ola Spjuth, Andreas Bender","doi":"10.1021/acs.chemrestox.4c00015","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00015","url":null,"abstract":"<p><p>Drug-induced liver injury (DILI) has been a significant challenge in drug discovery, often leading to clinical trial failures and necessitating drug withdrawals. Over the last decade, the existing suite of <i>in vitro</i> proxy-DILI assays has generally improved at identifying compounds with hepatotoxicity. However, there is considerable interest in enhancing the <i>in silico</i> prediction of DILI because it allows for evaluating large sets of compounds more quickly and cost-effectively, particularly in the early stages of projects. In this study, we aim to study ML models for DILI prediction that first predict nine proxy-DILI labels and then use them as features in addition to chemical structural features to predict DILI. The features include <i>in vitro</i> (e.g., mitochondrial toxicity, bile salt export pump inhibition) data, <i>in vivo</i> (e.g., preclinical rat hepatotoxicity studies) data, pharmacokinetic parameters of maximum concentration, structural fingerprints, and physicochemical parameters. We trained DILI-prediction models on 888 compounds from the DILI data set (composed of DILIst and DILIrank) and tested them on a held-out external test set of 223 compounds from the DILI data set. The best model, DILIPredictor, attained an AUC-ROC of 0.79. This model enabled the detection of the top 25 toxic compounds (2.68 LR+, positive likelihood ratio) compared to models using only structural features (1.65 LR+ score). Using feature interpretation from DILIPredictor, we identified the chemical substructures causing DILI and differentiated cases of DILI caused by compounds in animals but not in humans. For example, DILIPredictor correctly recognized 2-butoxyethanol as nontoxic in humans despite its hepatotoxicity in mice models. Overall, the DILIPredictor model improves the detection of compounds causing DILI with an improved differentiation between animal and human sensitivity and the potential for mechanism evaluation. DILIPredictor required only chemical structures as input for prediction and is publicly available at https://broad.io/DILIPredictor for use via web interface and with all code available for download.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141561884","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
Mass Spectrometric Detection and Differentiation of Enzymatically Active Abrin and Ricin Combined with a Novel Affinity Enrichment Technique. 结合新型亲和富集技术进行质谱检测并区分具有酶活性的阿布赖恩和蓖麻毒素
IF 3.7 3区 医学
Chemical Research in Toxicology Pub Date : 2024-07-04 DOI: 10.1021/acs.chemrestox.4c00149
Kaitlyn K Drinkard, John R Barr, Suzanne R Kalb
{"title":"Mass Spectrometric Detection and Differentiation of Enzymatically Active Abrin and Ricin Combined with a Novel Affinity Enrichment Technique.","authors":"Kaitlyn K Drinkard, John R Barr, Suzanne R Kalb","doi":"10.1021/acs.chemrestox.4c00149","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00149","url":null,"abstract":"<p><p>Abrin and ricin are toxic proteins produced by plants. Both proteins are composed of two subunits, an A-chain and a B-chain. The A-chain is responsible for the enzymatic activity, which causes toxicity. The B-chain binds to glycoproteins on the cell surface to direct the A-chain to its target. Both toxins depurinate 28S rRNA, making it impossible to differentiate these toxins based on only their enzymatic activity. We developed an analytical workflow for both ricin and abrin using a single method and sample. We have developed a novel affinity enrichment technique based on the ability of the B-chain to bind a glycoprotein, asialofetuin. After the toxin is extracted with asialofetuin-coated magnetic beads, an RNA substrate is added. Then, depurination is detected by a benchtop matrix-assisted laser desorption/ionization time-of-flight (MALDI TOF) mass spectrometer to determine the presence or absence of an active toxin. Next, the beads are subjected to tryptic digest. Toxin fingerprinting is done on a benchtop MALDI-TOF MS. We validated the assay through sensitivity and specificity studies and determined the limit of detection for each toxin as nanogram level for enzymatic activity and μg level for toxin fingerprinting. We examined potential cross-reactivity from proteins that are near neighbors of the toxins and examined potential false results in the presence of white powders.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496254","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
Pesticides and the Gut Microbiota: Implications for Parkinson's Disease. 农药与肠道微生物群:对帕金森病的影响。
IF 3.7 3区 医学
Chemical Research in Toxicology Pub Date : 2024-07-03 DOI: 10.1021/acs.chemrestox.4c00057
Nabanita Ghosh, Krishnendu Sinha, Parames C Sil
{"title":"Pesticides and the Gut Microbiota: Implications for Parkinson's Disease.","authors":"Nabanita Ghosh, Krishnendu Sinha, Parames C Sil","doi":"10.1021/acs.chemrestox.4c00057","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00057","url":null,"abstract":"<p><p>Parkinson's disease (PD) affects more people worldwide than just aging alone can explain. This is likely due to environmental influences, genetic makeup, and changes in daily habits. The disease develops in a complex way, with movement problems caused by Lewy bodies and the loss of dopamine-producing neurons. Some research suggests Lewy bodies might start in the gut, hinting at a connection between these structures and gut health in PD patients. These patients often have different gut bacteria and metabolites. Pesticides are known to increase the risk of PD, with evidence showing they harm more than just dopamine neurons. Long-term exposure to pesticides in food might affect the gut barrier, gut bacteria, and the blood-brain barrier, but the exact link is still unknown. This review looks at how pesticides and gut bacteria separately influence PD development and progression, highlighting the harmful effects of pesticides and changes in gut bacteria. We have examined the interaction between pesticides and gut bacteria in PD patients, summarizing how pesticides cause imbalances in gut bacteria, the resulting changes, and their overall effects on the PD prognosis.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489914","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
Free Radicals in Little Cigar Mainstream Smoke and the Potential Influence of Flavoring Chemicals on Free Radical Production. 小雪茄主流烟雾中的自由基以及调味化学品对自由基产生的潜在影响。
IF 3.7 3区 医学
Chemical Research in Toxicology Pub Date : 2024-07-02 DOI: 10.1021/acs.chemrestox.4c00044
Leanne Mocniak, Zachary T Bitzer, Reema Goel, Joshua E Muscat, Jonathan Foulds, Ryan J Elias, John P Richie
{"title":"Free Radicals in Little Cigar Mainstream Smoke and the Potential Influence of Flavoring Chemicals on Free Radical Production.","authors":"Leanne Mocniak, Zachary T Bitzer, Reema Goel, Joshua E Muscat, Jonathan Foulds, Ryan J Elias, John P Richie","doi":"10.1021/acs.chemrestox.4c00044","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00044","url":null,"abstract":"<p><p>Implementation of the Tobacco Control Act in 2009 banned characterizing flavors in cigarettes (except menthol and tobacco), but substitution has occurred by the continued availability of alternative flavored products (i.e., flavored little cigars). Little is known about how flavorants in noncigarette tobacco products impact human health. Thus, we investigated the impact of flavorants on free radical production in the mainstream smoke of little cigars. Gas- and particulate-phase free radical yields in mainstream smoke generated from 12 commercial little cigar brands and research little cigars and cigarettes were measured via electron paramagnetic resonance spectroscopy using the International Organization of Standardization (ISO) smoking protocol. Flavorants were extracted from unsmoked little cigars and analyzed by gas chromatography-mass spectroscopy. Gas- and particulate-phase radical yields from little cigars ranged from 13.5 to 97.6 and 0.453-1.175 nmol/unit, respectively. Comparatively, research cigarettes yielded an average of 4.9 nmol gas-phase radicals/unit and 0.292 nmol particulate-phase radicals/unit. From the products, 66 flavorants were identified, with each brand containing 4-24 individual flavorants. The free radical content was strongly correlated with the number of flavorants present in each cigar (<i>r</i> = 0.74, <i>p</i> = 0.01), indicating that highly flavored little cigars may produce higher levels of toxic free radicals. The presence of the flavorant ethyl methylphenylglycidate (strawberry) was associated with >2-fold higher levels of GP radicals (<i>p</i> = 0.001). Our results show that free radical delivery from little cigars is greater than that from research cigarettes and provide empirical evidence for the harmfulness of flavored tobacco products. Additionally, it demonstrates that flavorants present in combustible tobacco products can influence the levels of free radicals produced. Therefore, future tobacco product standards should consider little cigars.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489912","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
High Levels of BPA and BPF Exposure during Pregnancy Are Associated with Lower Birth Weight in Shenyang in Northeast China. 在中国东北沈阳,孕期双酚 A 和 BPF 暴露水平高与出生体重较低有关。
IF 3.7 3区 医学
Chemical Research in Toxicology Pub Date : 2024-07-02 DOI: 10.1021/acs.chemrestox.4c00145
Xuening Li, Qi Chen, Dan Wu, Zhe Xiao, Ce Shi, Youdan Dong, Lihong Jia
{"title":"High Levels of BPA and BPF Exposure during Pregnancy Are Associated with Lower Birth Weight in Shenyang in Northeast China.","authors":"Xuening Li, Qi Chen, Dan Wu, Zhe Xiao, Ce Shi, Youdan Dong, Lihong Jia","doi":"10.1021/acs.chemrestox.4c00145","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00145","url":null,"abstract":"<p><p>Animal studies indicate that bisphenol A (BPA) has obesogenic effects. Recent experiments reported similar endocrine-disrupting effects of bisphenol F (BPF) and bisphenol S (BPS), which are substitutes of BPA. The aim of this study was to investigate the exposure levels of these bisphenols in pregnant women and their effects on the physical development of infants aged 0-12 months. This study recruited pregnant women who gave birth at a hospital between February 2019 and September 2020. Urine samples from these pregnant women in the third trimester of pregnancy were detected by using ultrahigh-performance liquid chromatography-triple quadruple mass spectrometry. Follow-ups at 6 and 12 months of age were conducted by telephone by pediatricians using a structured questionnaire. Multiple linear regressions were used to determine the associations between bisphenol concentrations and infant weight. A total of 113 mother-child pairs had complete questionnaires and urine samples as well as data on newborns aged 6 months and 12 months. The detection rates of urinary BPA, BPF, and BPS in pregnant women were 100, 62.83, and 46.02%, respectively. Their median levels are 5.84, 0.54, and 0.07 μg/L, respectively. Increased urinary BPA and BPF concentrations during pregnancy were significantly associated with lower birth weight (standardized regression coefficients [β] = -0.081 kg, 95% confidence interval [CI]: -0.134 to -0.027; β = -0.049 kg, 95% CI: -0.097 to -0.001). In addition, urinary BPA and BPF concentrations during pregnancy were positively associated with weight growth rate from 0 to 6 months (β = 0.035 kg/mouth, 95% CI: 0.00-0.064; β = 0.028 kg/mouth, 95% CI: 0.006-0.050), especially in female infants (β = 0.054 kg/mouth, 95% CI: 0.015-0.093; β = 0.035 kg/mouth, 95% CI: 0.005-0.065). Therefore, maternal BPA and BPF levels during pregnancy were negatively correlated with birth weight and positively correlated with the growth rate of infant weight at 0-6 months of age, especially in female infants.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489913","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
Examining the Oxidation States of Metals in Aerosols Emitted by Electronic Cigarettes. 研究电子香烟排放的气溶胶中金属的氧化态。
IF 3.7 3区 医学
Chemical Research in Toxicology Pub Date : 2024-07-02 DOI: 10.1021/acs.chemrestox.4c00033
Kashala Fabrice Kapiamba, Stephen Yaw Owusu, Yangtao Wu, Yue-Wern Huang, Yi Jiang, Yang Wang
{"title":"Examining the Oxidation States of Metals in Aerosols Emitted by Electronic Cigarettes.","authors":"Kashala Fabrice Kapiamba, Stephen Yaw Owusu, Yangtao Wu, Yue-Wern Huang, Yi Jiang, Yang Wang","doi":"10.1021/acs.chemrestox.4c00033","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00033","url":null,"abstract":"<p><p>Electronic cigarettes (ECs) emit many toxic substances, including metals, that can pose a threat to users and the environment. The toxicity of the emitted metals depends on their oxidation states. Hence, this study examines the oxidation states of metals observed in EC aerosols. X-ray photoelectron spectroscopy analysis of the filters that collected EC aerosols identified the oxidation states of five primary metals (based on surface sample analysis), including chromium(III) (close to 100%) under low power setting while a noticeable amount of chromium(VI) (15%) at higher power settings of the EC, and copper(II) (100%), zinc(II) (100%), nickel(II) (100%), lead(II) (65%), and lead(IV) (35%) regardless of power settings. This observation indicates that the increased temperature due to higher power settings could alter the oxidation states of certain metals. We noted that many metals were in their lesser toxic states; however, inhaling these metals may still pose health risks.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489911","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
Harmful and Potentially Harmful Constituents in E-Liquids and Aerosols from Electronic Nicotine Delivery Systems (ENDS). 电子烟和电子尼古丁释放系统(ENDS)气溶胶中的有害和潜在有害成分。
IF 3.7 3区 医学
Chemical Research in Toxicology Pub Date : 2024-06-26 DOI: 10.1021/acs.chemrestox.4c00093
Samantha M Reilly, Tianrong Cheng, Charles Feng, Matthew J Walters
{"title":"Harmful and Potentially Harmful Constituents in E-Liquids and Aerosols from Electronic Nicotine Delivery Systems (ENDS).","authors":"Samantha M Reilly, Tianrong Cheng, Charles Feng, Matthew J Walters","doi":"10.1021/acs.chemrestox.4c00093","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00093","url":null,"abstract":"<p><p>In 2012, the U.S. Food & Drug Administration (FDA) published an established list of 93 harmful and potentially harmful constituents (HPHCs) targeting four tobacco product types (cigarettes, cigarette tobacco, roll-your-own tobacco, smokeless tobacco). In 2016, the FDA finalized the deeming rule to regulate electronic nicotine delivery systems (ENDS). However, knowledge gaps exist regarding whether certain HPHCs are present in ENDS e-liquids and aerosols. We identified and addressed these gaps by conducting literature searches and then experimentally quantifying HPHCs in the e-liquid and aerosol of 37 ENDS brands based on gaps in the literature. The literature searches identified 66 e-liquid HPHCs and 68 aerosol HPHCs that have limited to no information regarding the quantifiability of these constituents. A contracted ISO 17025 accredited laboratory performed the HPHC quantifications. The availability of validated analytical methods in the contracted laboratory determined the HPHCs included in the study scope (63/66 for e-liquids, 64/68 for aerosols). Combining the results from the quantifications and literature searches, 36 (39%) and 34 (37%) HPHCs were found quantifiable (≥limit of quantification [LOQ]) in ENDS e-liquids and aerosols, respectively, with 25 HPHCs being quantifiable in both matrices. Quantifiability results imply potential HPHC transfers between matrices, leaching from components, or formations from aerosol generation. The study results can inform the scientific basis for manufacturers and regulators regarding regulatory requirements for HPHC reporting. The HPHC quantities can also inform evaluations of the public health impact of ENDS and public communications regarding ENDS health risks.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141453622","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
Production of Peroxymonocarbonate by Steady-State Micromolar H2O2 and Activated Macrophages in the Presence of CO2/HCO3- Evidenced by Boronate Probes. 硼酸盐探针证明稳态微摩尔 H2O2 和活化巨噬细胞在 CO2/HCO3 存在下产生过氧碳酸氢盐。
IF 3.7 3区 医学
Chemical Research in Toxicology Pub Date : 2024-06-25 DOI: 10.1021/acs.chemrestox.4c00059
Edlaine Linares, Divinomar Severino, Daniela R Truzzi, Natalia Rios, Rafael Radi, Ohara Augusto
{"title":"Production of Peroxymonocarbonate by Steady-State Micromolar H<sub>2</sub>O<sub>2</sub> and Activated Macrophages in the Presence of CO<sub>2</sub>/HCO<sub>3</sub><sup>-</sup> Evidenced by Boronate Probes.","authors":"Edlaine Linares, Divinomar Severino, Daniela R Truzzi, Natalia Rios, Rafael Radi, Ohara Augusto","doi":"10.1021/acs.chemrestox.4c00059","DOIUrl":"10.1021/acs.chemrestox.4c00059","url":null,"abstract":"<p><p>Peroxymonocarbonate (HCO<sub>4</sub><sup>-</sup>/HOOCO<sub>2</sub><sup>-</sup>) is produced by the reversible reaction of CO<sub>2</sub>/HCO<sub>3</sub><sup>-</sup> with H<sub>2</sub>O<sub>2</sub> (<i>K</i> = 0.33 M<sup>-1</sup>, pH 7.0). Although produced in low yields at physiological pHs and H<sub>2</sub>O<sub>2</sub> and CO<sub>2</sub>/HCO<sub>3</sub><sup>-</sup> concentrations, HCO<sub>4</sub><sup>-</sup> oxidizes most nucleophiles with rate constants 10 to 100 times higher than those of H<sub>2</sub>O<sub>2</sub>. Boronate probes are known examples because HCO<sub>4</sub><sup>-</sup> reacts with coumarin-7-boronic acid pinacolate ester (CBE) with a rate constant that is approximately 100 times higher than that of H<sub>2</sub>O<sub>2</sub> and the same holds for fluorescein-boronate (Fl-B) as reported here. Therefore, we tested whether boronate probes could provide evidence for HCO<sub>4</sub><sup>-</sup> formation under biologically relevant conditions. Glucose/glucose oxidase/catalase were adjusted to produce low steady-state H<sub>2</sub>O<sub>2</sub> concentrations (2-18 μM) in Pi buffer at pH 7.4 and 37 °C. Then, CBE (100 μM) was added and fluorescence increase was monitored with time. The results showed that each steady-state H<sub>2</sub>O<sub>2</sub> concentration reacted more rapidly (∼30%) in the presence of CO<sub>2</sub>/HCO<sub>3</sub><sup>-</sup> (25 mM) than in its absence, and the data permitted the calculation of consistent rate constants. Also, RAW 264.7 macrophages were activated with phorbol 12-myristate 13-acetate (PMA) (1 μg/mL) at pH 7.4 and 37 °C to produce a time-dependent H<sub>2</sub>O<sub>2</sub> concentration (8.0 ± 2.5 μM after 60 min). The media contained 0, 21.6, or 42.2 mM HCO<sub>3</sub><sup>-</sup> equilibrated with 0, 5, or 10% CO<sub>2</sub>, respectively. In the presence of CBE or Fl-B (30 μM), a time-dependent increase in the fluorescence of the bulk solution was observed, which was higher in the presence of CO<sub>2</sub>/HCO<sub>3</sub><sup>-</sup> in a concentration-dependent manner. The Fl-B samples were also examined by fluorescence microscopy. Our results demonstrated that mammalian cells produce HCO<sub>4</sub><sup>-</sup> and boronate probes can evidence and distinguish it from H<sub>2</sub>O<sub>2</sub> under biologically relevant concentrations of H<sub>2</sub>O<sub>2</sub> and CO<sub>2</sub>/HCO<sub>3</sub><sup>-</sup>.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141445547","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
Immunological Drug-Drug Interactions Affect the Efficacy and Safety of Immune Checkpoint Inhibitor Therapies. 免疫学药物相互作用影响免疫检查点抑制剂疗法的疗效和安全性。
IF 3.7 3区 医学
Chemical Research in Toxicology Pub Date : 2024-06-24 DOI: 10.1021/acs.chemrestox.4c00067
Sophie Grice, Anna Olsson-Brown, Dean J Naisbitt, Sean Hammond
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