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Unraveling Interspecies Differences in the Phase I Hepatic Metabolism of Alternariol and Alternariol Monomethyl Ether: Closing Data Gaps for a Comprehensive Risk Assessment.
IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-07-19 DOI: 10.1021/acs.chemrestox.4c00095
Eszter Borsos, Elisabeth Varga, Georg Aichinger, Doris Marko

The Alternaria mycotoxins alternariol (AOH) and alternariol 9-O-monomethyl ether (AME) are pervasive food contaminants known to exert adverse effects in vitro, yet their toxicokinetics remain inadequately understood. Thus, this study endeavors to elucidate the qualitative and quantitative aspects of the phase I metabolism of AOH and AME. To pursue this goal, reduced nicotinamide adenine dinucleotide phosphate (NADPH)-fortified porcine, rat, and human liver microsomes were incubated for 0-10 min with AOH or AME within a concentration range of 1-100 and 1-50 μM, respectively. The decline in the parent toxin concentration was monitored via liquid chromatography coupled to tandem mass spectrometry, whereas coupling to high-resolution mass spectrometry provided insights into the composition of the arising metabolic mixture. The collected quantitative data allowed us to calculate the hepatic intrinsic clearance rates of AOH and AME, marking a notable contribution to the field. Moreover, we unveiled interspecies differences in the pattern and rate of the phase I metabolism of the investigated mycotoxins. The presented findings lay the groundwork for physiologically based toxicokinetic modeling aimed at estimating local concentrations of these mycotoxins in specific organs, enhancing our understanding of their mode of action and adverse health effects.

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引用次数: 0
One-Week Kava Dietary Supplementation Increases Both Urinary N- and O-Glucuronides of NNAL, a Lung Carcinogen Major Metabolite, among Smokers. 一周卡瓦膳食补充剂会增加吸烟者尿液中NNAL(一种肺致癌物的主要代谢物)的N-和O-葡萄糖醛酸。
IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-07-13 DOI: 10.1021/acs.chemrestox.4c00109
Qi Hu, Zhixin Tang, Allison Lynch, Breanne Freeman, Naomi Fujioka, Ramzi G Salloum, John Malaty, Frank A Orlando, Taimour Langaee, Zhiguang Huo, Chengguo Xing

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (commonly known as NNK) is one of the most prevalent and potent pulmonary carcinogens in tobacco products that increases the human lung cancer risk. Kava has the potential to reduce NNK and tobacco smoke-induced lung cancer risk by enhancing urinary excretion of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL, the major metabolite of NNK) and thus reducing NNK-induced DNA damage. In this study, we quantified N-glucuronidated NNAL (NNAL-N-gluc), O-glucuronidated NNAL (NNAL-O-gluc), and free NNAL in the urine samples collected before and after 1-week kava dietary supplementation. The results showed that kava increased both NNAL-N-glucuronidation and O-glucuronidation. Since NNAL-N-glucuronidation is dominantly catalyzed by UGT2B10, its representative single-nucleotide polymorphisms (SNPs) were analyzed among the clinical trial participants. Individuals with any of the four analyzed SNPs appear to have a reduced basal capacity in NNAL-N-glucuronidation. Among these individuals, kava also resulted in a smaller extent of increases in NNAL-N-glucuronidation, suggesting that participants with those UGT2B10 SNPs may not benefit as much from kava with respect to enhancing NNAL-N-glucuronidation. In summary, our results provide further evidence that kava enhances NNAL urinary detoxification via an increase in both N-glucuronidation and O-glucuronidation. UGT2B10 genetic status has not only the potential to predict the basal capacity of the participants in NNAL-N-glucuronidation but also potentially the extent of kava benefits.

4-(甲基亚硝基氨基)-1-(3-吡啶基)-1-丁酮(俗称 NNK)是烟草制品中最普遍和最有效的肺致癌物质之一,会增加人类患肺癌的风险。卡瓦通过增加尿液中 4-(甲基亚硝基氨基)-1-(3-吡啶基)-1-丁醇(NNAL,NNK 的主要代谢产物)的排泄量,从而减少 NNK 诱导的 DNA 损伤,从而有可能降低 NNK 和烟草烟雾诱发肺癌的风险。在这项研究中,我们对服用卡瓦膳食补充剂一周前后收集的尿液样本中的 N-葡萄糖醛酸化 NNAL(NNAL-N-gluc)、O-葡萄糖醛酸化 NNAL(NNAL-O-gluc)和游离 NNAL 进行了定量分析。结果表明,卡瓦能增加 NNAL-N-葡萄糖醛酸化和 O-葡萄糖醛酸化。由于 NNAL-N-葡萄糖醛酸化主要由 UGT2B10 催化,因此对临床试验参与者中具有代表性的单核苷酸多态性(SNPs)进行了分析。具有所分析的四个 SNPs 中的任何一个的人,其 NNAL-N-Glucuronidation 的基础能力似乎会降低。在这些人中,卡瓦也导致了 NNAL-N-葡萄糖醛酸化的较小程度的增加,这表明具有这些 UGT2B10 SNPs 的参与者可能不会从卡瓦增强 NNAL-N 葡萄糖醛酸化中获益太多。总之,我们的研究结果进一步证明,卡瓦能通过增加 N-葡萄糖醛酸和 O-葡萄糖醛酸来提高 NNAL 尿液的解毒能力。UGT2B10 遗传状态不仅有可能预测参与者在 NNAL-N-葡萄糖醛酸化中的基础能力,还有可能预测卡瓦益处的程度。
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引用次数: 0
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 Q2 CHEMISTRY, MEDICINAL 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

Nicotinamide riboside (NR), a NAD+ 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+ 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+ 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.

尼古丁酰胺核糖苷(NR)是一种 NAD+ 前体,因其在实验模型中产生的多种健康益处而备受关注。在培养细胞、动物和人体中进行的研究一致表明,补充 NR 后,NAD+ 的可用性增加,这被认为是 NR 作用于健康的唯一模式。在本研究中,我们发现在单层生长的 BEAS-2B 人体细胞的生长培养基中,持续摄入低浓度(1 μM)的 NR 会诱发能量应激,192 小时后细胞中的 NAD+ 会增加。在特定条件下,二维细胞培养模型中浓度大于 1 μM 的 NR 具有细胞毒性,而三维细胞培养模型(暴露于 1、5、10 和 50 μM NR 的 BEAS-2B 球形细胞)中测试的所有浓度都会诱发细胞凋亡。射枪蛋白质组学显示,NR 调节了蛋白质的丰度,这与观察到的对细胞能量代谢和细胞生长或存活的影响一致。能量应激可能会激活通路,从而带来健康益处,如预防癌症。因此,与表型正常的母本 BEAS-2B 细胞系相比,恶性前 1198 细胞系对 NR 的细胞毒性更敏感。低浓度 NR 诱导的轻微能量应激在其有益作用中所起的作用值得进一步研究。另一方面,提高 NR 生物利用率的策略需要关注可能产生的毒性效应。
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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 Q2 CHEMISTRY, MEDICINAL 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

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 in vitro proxy-DILI assays has generally improved at identifying compounds with hepatotoxicity. However, there is considerable interest in enhancing the in silico 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 in vitro (e.g., mitochondrial toxicity, bile salt export pump inhibition) data, in vivo (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.

药物诱导的肝损伤(DILI)一直是药物发现过程中面临的重大挑战,常常导致临床试验失败和不得不撤药。在过去的十年中,现有的体外替代 DILI 检测方法在鉴定具有肝毒性的化合物方面普遍有所改进。然而,人们对加强 DILI 的硅学预测相当感兴趣,因为这样可以更快、更经济地评估大量化合物,尤其是在项目的早期阶段。在本研究中,我们旨在研究用于 DILI 预测的 ML 模型,首先预测九个替代 DILI 标签,然后将它们作为化学结构特征之外的特征来预测 DILI。这些特征包括体外(如线粒体毒性、胆盐输出泵抑制)数据、体内(如临床前大鼠肝毒性研究)数据、最大浓度药代动力学参数、结构指纹和理化参数。我们对来自 DILI 数据集(由 DILIst 和 DILIrank 组成)的 888 种化合物进行了 DILI 预测模型的训练,并对来自 DILI 数据集的 223 种化合物进行了外部测试。最佳模型 DILIPredictor 的 AUC-ROC 为 0.79。与仅使用结构特征的模型(1.65 LR+ 分数)相比,该模型能够检测出前 25 种有毒化合物(2.68 LR+,正似然比)。利用 DILIPredictor 的特征解释,我们确定了导致 DILI 的化学子结构,并区分了由动物体内化合物而非人体内化合物导致的 DILI 病例。例如,尽管 2-丁氧基乙醇在小鼠模型中具有肝毒性,但 DILIPredictor 仍能正确识别出它对人类无毒。总之,DILIPredictor 模型提高了对导致 DILI 的化合物的检测能力,改进了动物和人体敏感性之间的区分,并具有机制评估的潜力。DILIPredictor 只需输入化学结构即可进行预测,可在 https://broad.io/DILIPredictor 网站上通过网络界面公开使用,所有代码均可下载。
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引用次数: 0
Enzymatic Acrolein Production System and Its Impact on Human Cells 酶促丙烯醛生产系统及其对人类细胞的影响
IF 4.1 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-07-09 DOI: 10.1021/acs.chemrestox.4c00119
Katherine A. Hurley, Jacob Folz, Jasmin Zgraggen, Tania N. Cruz, Sabine Diedrich, Shana J. Sturla
Acrolein is an environmental toxicant and is also generated by microbial metabolism in the intestinal tract. Aqueous acrolein rapidly dissipates from standard human cell culture media with nondetectable levels after 8 h, hindering cell-based studies to understand its biological impacts. Thus, we developed an extracellular acrolein biosynthesis system to continuously produce acrolein compatible with human cell culture conditions. The approach uses spermine as a precursor, amine oxidase found in fetal calf serum, and catalase to remove the hydrogen peroxide byproduct. We confirmed amine oxidase activity of calf serum using a colorimetric assay and further tested the requirement for catalase in the system to mitigate hydrogen peroxide-induced cytotoxicity. We calibrated responses of human colon cells to this enzymatic acrolein production system by comparing transcriptional responses, DNA adduct formation and cytotoxicity responses to either this system or pure acrolein exposures in a human colon cell line. Several genes related to oxidative stress including HMOX1, and the colorectal cancer-related gene SEMA4A were upregulated similarly between the enzymatic acrolein production system or pure acrolein. The acrolein-DNA adduct γ–OH-Acr-dG increased in a dose-dependent manner with spermine in the enzymatic acrolein production system, producing a maximum of 1065 adducts per 108 nucleosides when 400 μM spermine was used. This biosynthetic production method provides a relevant model for controlled acrolein exposure in cultured human cells and overcomes current limitations due to its physical properties and limited availability.
丙烯醛是一种环境毒物,也可由肠道中的微生物代谢产生。水性丙烯醛会迅速从标准人类细胞培养基中消散,8 小时后其含量将无法检测到,这阻碍了基于细胞的研究以了解其对生物的影响。因此,我们开发了一种细胞外丙烯醛生物合成系统,以持续产生符合人体细胞培养条件的丙烯醛。该方法使用精胺作为前体,使用胎牛血清中的胺氧化酶和过氧化氢酶去除过氧化氢副产物。我们利用比色测定法确认了小牛血清中胺氧化酶的活性,并进一步测试了该系统是否需要过氧化氢酶来减轻过氧化氢诱导的细胞毒性。我们通过比较转录反应、DNA 加合物形成以及人结肠细胞系对该系统或纯丙烯醛暴露的细胞毒性反应,校准了人结肠细胞对这种酶法丙烯醛生产系统的反应。与氧化应激有关的几个基因,包括 HMOX1 和结肠直肠癌相关基因 SEMA4A,在酶法丙烯醛生产系统或纯丙烯醛中都有类似的上调。在酶法丙烯醛生产系统中,丙烯醛-DNA 加合物 γ-OH-Acr-dG 的增加与精胺的剂量有关,当使用 400 μM 的精胺时,每 108 个核苷酸最多可产生 1065 个加合物。这种生物合成生产方法为控制培养人体细胞中的丙烯醛暴露提供了一个相关模型,并克服了目前由于其物理性质和供应有限而造成的局限性。
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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 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-07-04 DOI: 10.1021/acs.chemrestox.4c00149
Kaitlyn K. Drinkard, John R. Barr and Suzanne R. Kalb*, 

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.

蓖麻毒蛋白和蓖麻毒素是植物产生的有毒蛋白质。这两种蛋白质都由两个亚基组成,即 A 链和 B 链。A 链负责酶活性,从而产生毒性。B 链与细胞表面的糖蛋白结合,引导 A 链到达目标。这两种毒素都会使 28S rRNA 去嘌呤,因此无法仅根据酶活性来区分这些毒素。我们开发了一种使用单一方法和样品同时分析蓖麻毒素和蓖麻蛋白的工作流程。我们根据 B 链与糖蛋白(asialofetuin)的结合能力开发了一种新的亲和富集技术。用涂有阿糖蛋白的磁珠提取毒素后,加入 RNA 底物。然后,用台式基质辅助激光解吸/电离飞行时间(MALDI TOF)质谱仪检测脱urination,以确定是否存在活性毒素。接着,对珠子进行胰蛋白酶消化。毒素指纹图谱在台式 MALDI-TOF MS 上完成。我们通过灵敏度和特异性研究验证了该检测方法,并确定了每种毒素的检测限:酶活性检测限为纳克级,毒素指纹图谱检测限为微克级。我们研究了与毒素近邻的蛋白质可能产生的交叉反应,并研究了存在白色粉末时可能出现的错误结果。
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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 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-07-03 DOI: 10.1021/acs.chemrestox.4c00057
Nabanita Ghosh, Krishnendu Sinha* and Parames C. Sil*, 

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.

帕金森病(Parkinson's disease,PD)在全球范围内的患病人数远远超过了衰老本身所能解释的范围。这可能是由于环境影响、基因构成和日常习惯的改变造成的。帕金森病的发病过程十分复杂,路易体和产生多巴胺的神经元的缺失会导致运动障碍。一些研究表明路易体可能始于肠道,这暗示着这些结构与帕金森病患者的肠道健康之间存在联系。这些患者的肠道细菌和代谢物往往不同。众所周知,杀虫剂会增加罹患帕金森病的风险,有证据表明杀虫剂伤害的不仅仅是多巴胺神经元。长期接触食物中的杀虫剂可能会影响肠道屏障、肠道细菌和血脑屏障,但其中的确切联系尚不清楚。这篇综述探讨了杀虫剂和肠道细菌如何分别影响帕金森病的发生和发展,强调了杀虫剂的有害作用和肠道细菌的变化。我们研究了帕金森病患者体内杀虫剂与肠道细菌之间的相互作用,总结了杀虫剂如何导致肠道细菌失衡、由此产生的变化及其对帕金森病预后的总体影响。
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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 Q2 CHEMISTRY, MEDICINAL 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 and John P. Richie, 

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 (r = 0.74, p = 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 (p = 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.

2009 年实施的《烟草控制法案》禁止在卷烟(薄荷和烟草除外)中使用特征香料,但替代香料产品(如带香味的小雪茄)的持续供应起到了替代作用。人们对非卷烟烟草制品中的香料如何影响人体健康知之甚少。因此,我们研究了香料对小雪茄主流烟雾中自由基产生的影响。我们采用国际标准化组织(ISO)的吸烟规程,通过电子顺磁共振光谱法测量了 12 个商业小雪茄品牌以及研究小雪茄和香烟产生的主流烟雾中的气相和微粒相自由基产量。从未吸过的小雪茄中提取香料,并通过气相色谱-质谱法进行分析。小雪茄的气相和微粒相自由基产量分别为 13.5 至 97.6 纳摩尔/单位和 0.453 至 1.175 纳摩尔/单位。相比之下,研究型香烟的平均气相自由基产量为 4.9 nmol/单位,颗粒相自由基产量为 0.292 nmol/单位。从产品中确定了 66 种香料,每个品牌含有 4-24 种香料。自由基含量与每支雪茄中香料的数量密切相关(r = 0.74,p = 0.01),这表明高香料含量的小雪茄可能会产生更高水平的有毒自由基。香料甲基苯基甘氨酸乙酯(草莓)的存在与 GP 自由基水平高出 2 倍以上有关(p = 0.001)。我们的研究结果表明,小雪茄释放的自由基比研究型香烟释放的自由基更多,这为香料烟草产品的危害性提供了实证。此外,它还证明了可燃烟草制品中的香料会影响自由基的产生水平。因此,未来的烟草产品标准应考虑小雪茄。
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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 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-07-02 DOI: 10.1021/acs.chemrestox.4c00145
Xuening Li, Qi Chen, Dan Wu, Zhe Xiao, Ce Shi, Youdan Dong* and Lihong Jia*, 

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.

动物实验表明,双酚 A(BPA)具有致肥作用。最近的实验报告称,双酚 F(BPF)和双酚 S(BPS)(双酚 A 的替代品)也有类似的内分泌干扰作用。本研究旨在调查孕妇接触这些双酚的水平及其对 0-12 个月婴儿身体发育的影响。这项研究招募了 2019 年 2 月至 2020 年 9 月期间在一家医院分娩的孕妇。采用超高效液相色谱-三重四极杆质谱法检测了这些孕妇在怀孕三个月时的尿液样本。6个月和12个月大时,儿科医生通过电话使用结构化问卷进行随访。采用多元线性回归法确定双酚浓度与婴儿体重之间的关系。共有 113 对母子获得了完整的调查问卷和尿液样本,以及新生儿 6 个月和 12 个月的数据。孕妇尿液中双酚 A、双酚 F 和双酚 S 的检出率分别为 100%、62.83% 和 46.02%。它们的中位含量分别为 5.84、0.54 和 0.07 微克/升。孕期尿液中双酚 A 和双酚 F 浓度的增加与出生体重的降低显著相关(标准化回归系数 [β] = -0.081 千克,95% 置信区间 [CI]:-0.134 至 -0.027;β = -0.049 千克,95% 置信区间:-0.097 至 -0.001)。此外,孕期尿液中的双酚 A 和双酚 F 浓度与 0 至 6 个月的体重增长率呈正相关(β = 0.035 千克/口,95% CI:0.00-0.064;β = 0.028 千克/口,95% CI:0.006-0.050),尤其是女婴(β = 0.054 千克/口,95% CI:0.015-0.093;β = 0.035 千克/口,95% CI:0.005-0.065)。因此,孕期母体双酚 A 和 BPF 水平与婴儿出生体重呈负相关,而与婴儿 0-6 个月大时的体重增长率呈正相关,尤其是对女婴而言。
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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 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-07-02 DOI: 10.1021/acs.chemrestox.4c00033
Kashala Fabrice Kapiamba, Stephen Yaw Owusu, Yangtao Wu, Yue-Wern Huang, Yi Jiang and Yang Wang*, 

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.

电子香烟(EC)会释放出包括金属在内的多种有毒物质,对使用者和环境造成威胁。所排放金属的毒性取决于其氧化态。因此,本研究对在电子烟气溶胶中观察到的金属氧化态进行了研究。這項研究利用 X 射線光電子譜法分析收集電子濾波器氣溶膠的濾網, 結果發現五種主要金屬的氧化態(根據表面樣本分析),包括在低功率設 定下接近 100%的鉻(III),而在較高功率設定下則有顯著數量的鉻(VI)(15%), 以及不論功率設定為何的銅(II)(100%)、鋅(II)(100%)、鎳(II)(100%)、 鉛(II)(65%)和鉛(IV)(35%)。这一观察结果表明,较高的功率设置导致的温度升高可能会改变某些金属的氧化态。我们注意到,许多金属处于毒性较低的状态,但吸入这些金属仍可能对健康造成危害。
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引用次数: 0
期刊
Chemical Research in Toxicology
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