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Runaway uncoupling in 2,4-dinitrophenol poisoning: Clinical and mitochondrial observations from two cases 2,4-二硝基苯酚中毒失控解偶联：两例临床和线粒体观察

Q1 Environmental Science

Toxicology Reports

Pub Date : 2025-12-08 DOI: 10.1016/j.toxrep.2025.102183

Erik Lindeman , Tine Sommer , Märta Leffler , Shusuke Sekine , Eskil Elmér , Fredrik Sjövall , Wilhelm Wallquist

2,4-Dinitrophenol (DNP) is a potent mitochondrial uncoupler briefly marketed in the 1930s as a weight-reducing agent before being banned by the FDA after reports of severe toxicity. Since the early 2000s, DNP has reemerged as an illicit “fat-burner”, causing characteristic metabolic disturbances with a high risk of fatal outcome. We describe two Swedish cases of DNP poisoning: one fatal after suicidal ingestion and one non-fatal after use for weight reduction. Clinical data, mitochondrial respirometry, and analysis of gas exchange and ventilatory dynamics were used to characterize the metabolic disturbances under intensive care. The fatal case progressed within hours to respiratory acidosis, hyperthermia, severe hyperkalemia, and peri-mortem rigidity consistent with catastrophic ATP depletion. The non-fatal case showed similar but reversible toxicity, with sustained yet manageable hypermetabolism lasting more than a week. Serial platelet respirometry demonstrated a marked initial increase in uncoupled respiration, followed by a progressive decline with a functional half-life of 4.9 days. Together, these cases suggest a self-amplifying feedback loop central to DNP toxicity, in which excessive CO₂ production from mitochondrial uncoupling causes local acidosis that enhances mitochondrial DNP uptake. Glucose supplementation and hyperkalemia management are essential supportive measures, whereas active cooling and high minute ventilation may blunt this self-reinforcing metabolic acceleration. Severe poisoning may result in a state of “runaway uncoupling,” a term we propose for the catastrophic progression to death observed in numerous DNP poisonings. This feedback loop illustrates the unpredictable toxicokinetics of DNP and reinforces the FDA’s early conclusion: DNP is “unfit for human consumption”.

2,4-二硝基苯酚（DNP）是一种有效的线粒体解偶联剂，曾在20世纪30年代作为减肥剂短暂上市，但在有严重毒性报告后被FDA禁止。自21世纪初以来，DNP作为一种非法的“脂肪燃烧器”重新出现，导致具有高风险致命后果的特征性代谢紊乱。我们描述了两个瑞典病例DNP中毒：一个致命后自杀摄入和一个非致命后使用减肥。临床资料、线粒体呼吸测量、气体交换和呼吸动力学分析用于表征重症监护下的代谢紊乱。死亡病例在数小时内发展为呼吸性酸中毒、高热、严重高钾血症和死前僵硬，与灾难性ATP耗尽一致。非致命性病例表现出类似但可逆的毒性，持续但可控的高代谢持续超过一周。连续血小板呼吸测定显示，非偶联呼吸的初始显著增加，随后逐渐下降，功能半衰期为4.9天。总之，这些病例表明了DNP毒性的自我放大反馈回路，其中线粒体解偶联产生的过量CO 2导致局部酸中毒，从而增强线粒体DNP的摄取。葡萄糖补充和高钾血症管理是必要的支持措施，而主动冷却和高分钟通气可能会减弱这种自我强化的代谢加速。严重的中毒可能导致“失控解耦”状态，我们提出了一个术语，用于在许多DNP中毒中观察到的灾难性的死亡进程。这种反馈循环说明了DNP不可预测的毒性动力学，并强化了FDA的早期结论：DNP“不适合人类食用”。

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引用次数: 0

Can in silico models predict drug-induced cardiac risk in vulnerable populations? 计算机模型能否预测易感人群药物引起的心脏风险？

Q1 Environmental Science

Toxicology Reports

Pub Date : 2025-12-08 DOI: 10.1016/j.toxrep.2025.102179

Paula Dominguez-Gomez , Pablo Gonzalez-Martin , Laura Baldo-Canut , Eva Casoni , Ani Amar , Jose M. Pozo , Constantine Butakoff , Mariano Vazquez , Jazmin Aguado-Sierra

This study evaluates virtual cardiac populations for preclinical assessment of drug-induced QT interval prolongation and arrhythmic risk. Traditional predictions often rely on small, healthy cohorts, excluding vulnerable populations. Using computational models of realistic heart anatomies and electrophysiology, we generated a virtual cohort of 512 subjects across healthy and diseased hearts (heart failure, dilated and hypertrophic cardiomyopathy, ischaemia, and myocardial infarction). We assessed QT prolongation and arrhythmic events following administration of moxifloxacin (benchmark antibiotic) and contraindicated drugs including quinidine, bepridil, and flecainide.

Patients with heart failure, hypertrophic and dilated cardiomyopathy showed greater QT prolongation to moxifloxacin, unlike ischaemia and myocardial infarction, which resembled healthy subjects. Females exhibited consistently higher QT prolongation than males. Contraindicated drugs markedly increased arrhythmia risk in populations with heart failure, dilated and hypertrophic cardiomyopathy, and ischaemia, frequently leading to lethal arrhythmias such as Torsades des Pointes or ventricular fibrillation, particularly in females.

These findings demonstrate that computational models capture variability in drug response across pathologies and sexes, offering a predictive framework for preclinical safety evaluations and supporting safer, more personalized drug development strategies.

本研究对虚拟心脏人群进行药物诱导QT间期延长和心律失常风险的临床前评估。传统的预测往往依赖于小的、健康的群体，不包括弱势群体。利用真实心脏解剖和电生理学的计算模型，我们创建了一个虚拟队列，包括健康和患病心脏（心力衰竭、扩张型和肥厚型心肌病、缺血和心肌梗死）的512名受试者。我们评估了在给予莫西沙星（基准抗生素）和禁忌药物包括奎尼丁、贝普利地尔和氟氯胺后QT间期延长和心律失常事件。心衰、肥厚和扩张型心肌病患者与缺血和心肌梗死患者不同，莫西沙星作用下QT间期延长时间更长。女性QT间期延长始终高于男性。在患有心力衰竭、扩张型和肥厚型心肌病以及缺血的人群中，禁忌症药物显著增加心律失常的风险，经常导致致命性心律失常，如尖角扭转或心室颤动，特别是在女性中。这些发现表明，计算模型捕获了不同病理和性别的药物反应差异，为临床前安全性评估提供了预测框架，并支持更安全、更个性化的药物开发策略。

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引用次数: 0

Collateral damage: Cardiovascular and respiratory implications of tear gas deployment during peaceful protest 附带损害：和平抗议期间使用催泪瓦斯对心血管和呼吸系统的影响

Q1 Environmental Science

Toxicology Reports

Pub Date : 2025-12-01 DOI: 10.1016/j.toxrep.2025.102166

Konstantine Chakhunashvili , Gela Gunashvili , Nino Jobava , George Chakhunashvili , Davit G. Chakhunashvili

Background

In December 2024, large-scale protests in front of Georgia’s Parliament were met with crowd-control measures involving the widespread use of tear gas and pepper spray, mixed with water. This study examined whether protest participants exposed to these agents exhibited electrocardiographic, capillaroscopic, or hematologic abnormalities, and explored associations with allergy status, mask use, and attendance frequency.

Methods

An observational case-control study was conducted from January 9 to March 1, 2025. Of 347 protest participants surveyed, 69 underwent clinical evaluation. A control group of 31 unexposed individuals was recruited. Participants received ECGs, capillaroscopy, complete blood count (CBC), and coagulogram testing. Data were analyzed using chi-square tests, eta coefficients, and t-tests (p < 0.05).

Results

ECG abnormalities—including P-wave (p < 0.001), QRS complex (p = 0.035), and T-wave (p = 0.012) changes—were significantly more frequent in the exposed group. Right bundle branch block and T-wave inversions were particularly notable. Capillaroscopy showed more non-specific and sclerodermal abnormalities in the exposed group, though not statistically significant. Allergy status was linked to higher symptom burden, while mask use and attendance frequency were not predictive. Laboratory parameters were largely normal. Two respiratory cases—hypersensitivity pneumonitis and unresolved pneumonia—were clinically linked to exposure.

Conclusion

Exposure to CS gas was associated with significant ECG changes, indicating potential cardiopulmonary effects. Clinical patterns and rare respiratory cases warrant re-evaluation of chemical agent use, improved oversight, and long-term studies to assess chronic health risks in exposed populations.

2024年12月，格鲁吉亚议会前的大规模抗议活动遭遇了人群控制措施，包括广泛使用催泪瓦斯和胡椒喷雾，与水混合。本研究调查了暴露于这些药物的抗议参与者是否表现出心电图、毛细血管镜或血液学异常，并探讨了过敏状态、口罩使用和出勤频率的关系。方法于2025年1月9日至3月1日进行观察性病例对照研究。在接受调查的347名抗议参与者中，69人接受了临床评估。研究人员招募了31名未接触过病毒的人作为对照组。参与者接受了心电图、毛细血管镜检查、全血细胞计数（CBC）和凝血图测试。数据分析采用卡方检验、eta系数和t检验（p <； 0.05）。结果暴露组secg异常包括p波（p <； 0.001）、QRS复合体（p = 0.035）和t波（p = 0.012）变化明显高于暴露组。右束分支阻滞和t波反转尤为显著。暴露组的毛细血管镜检查显示非特异性和硬皮异常较多，但无统计学意义。过敏状态与较高的症状负担有关，而口罩的使用和出勤频率并不具有预测性。实验室参数基本正常。两个呼吸道病例——过敏性肺炎和未解决的肺炎——在临床上与暴露有关。结论暴露于CS气体与显著的心电图变化相关，提示潜在的心肺影响。临床模式和罕见呼吸道病例需要重新评估化学剂的使用，改进监督，并进行长期研究，以评估接触人群的慢性健康风险。

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引用次数: 0

Cytotoxic and oxidative effects of commercially available propylene glycol (PG) and vegetable glycerin (VG): Common humectants in electronic cigarettes 市售丙二醇（PG）和植物甘油（VG）的细胞毒性和氧化作用：电子烟中常见的湿润剂

Q1 Environmental Science

Toxicology Reports

Pub Date : 2025-12-01 DOI: 10.1016/j.toxrep.2025.102171

Yehao Sun , Gagandeep Kaur , Felix Effah , Alan Friedman , Irfan Rahman

The effects of commercially available brands of common e-liquid humectants – propylene glycol (PG) and vegetable glycerin (VG) are not known. This study evaluates the toxicities of commercially available PG and VG mixtures compared to their analytically pure grade chemicals. The pH and the viscosity of 50:50 PG/VG mixtures from four different commercially available brands and a pure chemical mixture were measured. Commercially available brands of PG/VG generally had higher pH (up to ∼6.25) and viscosity values (up to 16.4 %) than the pure chemical mixture (pH = 5.5; viscosity = 12.9 %). GC-MS spectra provide evidence of impurities in commercially available PG, but not VG liquids when compared to pure chemicals. While we observe variation in the level of acellular reactive oxygen species generated by commercial mixtures as compared to the pure chemical, the protein carbonylation levels were comparable for both the mixtures, thus indicating variation in the nature of the oxygen species generated upon aerosolization. No noticeable change was observed upon studying the human monocytic U937 cellular responses upon treatment with sub-toxic concentrations of PG/VG mixtures; however, a decrease in the basal IL-8 production was observed at higher concentrations (1 %) of PG/VG treatment. The commercially available PG/VG mixtures show comparable oxidative and biological effects to the pure chemical. However, GC-MS data identified impurities which may explain our observation of a variable ROS profile in each PG/VG mixture. Future work on the brand-specific toxicity of PG/VG or its usage is warranted to inform regulatory guidelines for e-cigarettes.

市售品牌的常见电子液体湿润剂——丙二醇（PG）和植物甘油（VG）的效果尚不清楚。本研究评估了市售的PG和VG混合物与其分析纯级化学品的毒性。测量了四种不同市售品牌50:50 PG/VG混合物和纯化学混合物的pH和粘度。市售品牌的PG/VG通常比纯化学混合物（pH = 5.5，粘度= 12.9 %）具有更高的pH值（高达~ 6.25）和粘度值（高达16.4 %）。GC-MS光谱提供了商用PG中杂质的证据，但与纯化学品相比，VG液体中没有杂质。虽然我们观察到与纯化学混合物相比，商业混合物产生的脱细胞活性氧水平存在差异，但两种混合物的蛋白质羰基化水平是相似的，从而表明在雾化过程中产生的氧的性质存在差异。在研究亚毒性浓度PG/VG混合物对人单核细胞U937的反应时，未观察到明显的变化；然而，在较高浓度（1 %）的PG/VG处理下，基础IL-8产量下降。市售的PG/VG混合物显示出与纯化学的相当的氧化和生物效应。然而，GC-MS数据发现了杂质，这可能解释了我们在每种PG/VG混合物中观察到的可变ROS谱。未来有必要对PG/VG的品牌毒性或其使用进行研究，为电子烟的监管指南提供信息。

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引用次数: 0

Modulating morphine-induced conditioned place preference: The role of diclofenac sodium 调节吗啡诱导的条件位置偏好：双氯芬酸钠的作用

Q1 Environmental Science

Toxicology Reports

Pub Date : 2025-12-01 DOI: 10.1016/j.toxrep.2025.102174

Haneen Amawi , Rawan Alhazaimeh , Alaa M. Hammad , Aseel O. Rataan , Sahar Alsheyab , Tayma Maklouf , Bahaa Al-Trad , Karem H. Alzoubi

Morphine is known to induce strong reward-related behaviors, contributing to its high addiction potential. Non-steroidal anti-inflammatory drugs (NSAIDs), such as diclofenac sodium, have been suggested to modulate neuroinflammatory pathways involved in addiction. This study aimed to evaluate the effect of diclofenac sodium on morphine-induced conditioned place preference (CPP) in rats and investigate its underlying anti-inflammatory and antioxidant mechanisms. Female rats were subjected to a morphine-induced conditioned place preference (CPP) protocol. Diclofenac sodium (25 mg/kg) was administered 30 min prior to morphine conditioning sessions via injection. Post-conditioning, brain tissue samples were analyzed to measure the mRNA expression levels of cyclooxygenase enzymes (Cox1, Cox2), nuclear factor kappa B (Nf-κB), interleukin-6 (Il-6), and interleukin-1β (Il-1β). Oxidative stress in serum samples was assessed through catalase (CAT), superoxide dismutase (SOD), and myeloperoxidase (MPO) enzyme activity. Morphine significantly induced CPP, indicating a strong reward effect. Diclofenac sodium administration markedly attenuated this morphine-induced seeking behavior. This behavioral effect was accompanied by a significant reduction in the expression levels of cox1, cox2, nf-κB, and il-6, and a significant increase in il-1β mRNA levels compared to the morphine group. Additionally, diclofenac sodium significantly reduced oxidative stress, as indicated by decreased SOD activity when combined with morphine compared to the morphine group. In conclusion, Diclofenac sodium effectively attenuates morphine-induced reward behavior in the CPP model, potentially through modulation of inflammatory and oxidative stress pathways. These findings support the therapeutic potential of diclofenac sodium in managing opioid-seeking behaviors and provide insights into its anti-inflammatory and antioxidant mechanisms of action.

众所周知，吗啡会诱发强烈的奖励相关行为，这是其高成瘾性的原因之一。非甾体抗炎药（NSAIDs），如双氯芬酸钠，被认为可以调节与成瘾有关的神经炎症通路。本研究旨在评价双氯芬酸钠对吗啡诱导的大鼠条件位置偏好（CPP）的影响，并探讨其抗炎和抗氧化机制。雌性大鼠进行吗啡诱导的条件位置偏好（CPP）实验。双氯芬酸钠（25 mg/kg）在吗啡调节前30 分钟注射。预处理后，分析脑组织样品，测定环氧化酶（Cox1、Cox2）、核因子κB （Nf-κB）、白细胞介素-6 （Il-6）、白细胞介素-1β (Il-1β) mRNA表达水平。通过过氧化氢酶（CAT）、超氧化物歧化酶（SOD）和髓过氧化物酶（MPO）活性来评估血清样品的氧化应激。吗啡显著诱导CPP，提示较强的奖赏效应。双氯芬酸钠可显著减弱吗啡诱导的寻找行为。与吗啡组相比，这种行为效应伴随着cox1、cox2、nf-κB和il-6的表达水平显著降低，il-1β mRNA水平显著升高。此外，双氯芬酸钠显著降低氧化应激，与吗啡组相比，与吗啡联合使用时SOD活性降低。综上所述，双氯芬酸钠可能通过调节炎症和氧化应激途径，有效地减弱吗啡诱导的CPP模型中的奖励行为。这些发现支持双氯芬酸钠在控制阿片类药物寻求行为方面的治疗潜力，并为其抗炎和抗氧化作用机制提供了见解。

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引用次数: 0

Massive caffeine overdose with extremely high blood caffeine concentration and prolonged toxidrome 大量咖啡因过量，血液中咖啡因浓度极高，长时间中毒

Q1 Environmental Science

Toxicology Reports

Pub Date : 2025-12-01 DOI: 10.1016/j.toxrep.2025.102177

Yuka Okazaki , Suguru Hitomi , Shigemasa Taguchi , Ryoko Kyan , Tomohiro Yoshizawa , Yoshito Kamijo , Tomoki Hanazawa , Kazuya Kiyota

The easy availability of caffeine has led to an increased risk of ingesting toxic levels in recent years. Although several studies reported severe and fatal cases of massive caffeine poisoning, few cases of caffeine overdose with a protracted toxidrome have been described. We present the case of a 37-year-old man with a massive caffeine overdose. He presented with altered consciousness and non-sustained ventricular tachycardia and was intubated and placed on continuous venovenous hemodiafiltration. The patient was extubated but had to be reintubated on day 4 because of altered consciousness, tachypnea, and tachycardia. His renal and hepatic dysfunction worsened, requiring three sessions of hemodialysis. The patient was eventually extubated on day 8, without worsening of symptoms. The present case illustrates high caffeine concentration as a cause of prolonged toxidrome with hepatic and renal damage.

近年来，咖啡因的易得性导致摄入有毒水平的风险增加。尽管有几项研究报道了大量咖啡因中毒的严重和致命病例，但很少有咖啡因过量导致长期中毒的病例被描述。我们报告一个37岁的男性咖啡因过量的病例。他表现为意识改变和非持续性室性心动过速，插管并进行持续静脉-静脉血液滤过。患者拔管，但由于意识改变、呼吸急促和心动过速，不得不在第4天重新插管。他的肾功能和肝功能恶化，需要进行三次血液透析。患者最终在第8天拔管，症状没有恶化。本病例说明高咖啡因浓度是引起长期氧化症并肝和肾损害的原因。

引用次数: 0

Investigating a novel solid-state oxygenating therapeutic: Influence on oxidative stress and cellular responses in human lung cells 研究一种新型固态氧合疗法：对人肺细胞氧化应激和细胞反应的影响

Q1 Environmental Science

Toxicology Reports

Pub Date : 2025-12-01 DOI: 10.1016/j.toxrep.2025.102173

Ashleigh A. Jarrous , Asha Ashraf , Sini Macheri , Erica D. Bruce

Hypoxia is a common pathological state found in a diverse array of diseases, including those associated with pulmonary dysfunctions such as ARDS, COPD, and emphysema. BaylorOx is a novel solid-state oxygenating therapeutic that aims to supplement current oxygenating therapies by supplying 8–15 times more oxygen than human hemoglobin. While increased O2 levels can alleviate cellular damage associated with hypoxia, supraphysiological oxygen levels can also produce reactive oxygen species (ROS), which can lead to oxidative stress at elevated levels. Due to BaylorOx’s high oxygen capacity, it is essential to determine whether this novel drug has any indication of causing oxidative stress. The goal of this study was, firstly, to investigate the cytotoxicity of BUOx on the human bronchial epithelial (BEAS-2B) and adenocarcinoma human alveolar basal epithelial (A549) cell lines under standard and hypoxic atmospheric conditions. Cytotoxicity was measured by performing the lactate dehydrogenase (LDH) and MTT cell viability assays. The second aim of this study was to determine the effects of BUOx on oxidative stress in the BEAS-2B and A549 cell lines. ROS production was measured using the DCFH-DA assay after 24 h. exposure to BUOx and 48 h. incubation in hypoxic or normoxic conditions. From the cell viability assays, BUOx showed no signs of cytotoxicity up to doses as high as 100 ppm. Interestingly, ROS production, as determined through the DCFH-DA assay, differed between the BEAS-2B and A549 cell lines following treatment with BUOx. While BUOx did not cause a significant increase in ROS production at either tested dose on the BEAS-2B cell line, a significant increase in ROS production was seen at a 10-ppm dose in the A549s. This suggests that BUOx’s mechanism of action may vary between different cell types and selectively cause oxidative stress in cancer cells. Overall, these findings suggest that BUOx may be an effective and safe alternative to current oxygen therapies, especially for the treatment of acute pulmonary dysfunctions associated with hypoxia. Further research is required to confirm BUOx’s effects on oxidative stress and its potential as an anti-cancer agent.

缺氧是多种疾病中常见的病理状态，包括与肺功能障碍相关的疾病，如ARDS、COPD和肺气肿。BaylorOx是一种新型的固态氧合疗法，旨在通过提供比人类血红蛋白多8-15 倍的氧气来补充目前的氧合疗法。虽然增加的氧气水平可以减轻与缺氧相关的细胞损伤，但超生理氧水平也可以产生活性氧（ROS），从而导致氧化应激水平升高。由于BaylorOx的高氧容量，确定这种新药是否有引起氧化应激的迹象是至关重要的。本研究的目的首先是研究在标准和低氧大气条件下BUOx对人支气管上皮细胞（BEAS-2B）和腺癌人肺泡基底上皮细胞（A549）的细胞毒性。通过乳酸脱氢酶（LDH）和MTT细胞活力测定测定细胞毒性。本研究的第二个目的是确定BUOx对BEAS-2B和A549细胞系氧化应激的影响。24 h后用DCFH-DA法测定ROS生成。暴露于BUOx和48 h。在低氧或常氧条件下孵育。从细胞活力测定来看，即使剂量高达100 ppm， BUOx也没有显示出细胞毒性的迹象。有趣的是，通过DCFH-DA测定，BUOx处理后的BEAS-2B和A549细胞系的ROS生成有所不同。虽然BUOx在BEAS-2B细胞系上的两种测试剂量都没有引起ROS产生的显着增加，但在A549s中，10 ppm剂量的ROS产生显着增加。这表明BUOx的作用机制可能在不同的细胞类型之间有所不同，并选择性地引起癌细胞的氧化应激。总的来说，这些发现表明，BUOx可能是目前氧疗法的有效和安全的替代方案，特别是对于治疗与缺氧相关的急性肺功能障碍。需要进一步的研究来证实BUOx对氧化应激的影响及其作为抗癌剂的潜力。

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引用次数: 0

Lemborexant overdose presenting with mild sedation despite high plasma levels: A case report Lemborexant过量表现为轻度镇静，尽管高血浆水平：1例报告

Q1 Environmental Science

Toxicology Reports

Pub Date : 2025-12-01 DOI: 10.1016/j.toxrep.2025.102172

Makoto Suzuki, Daisuke Usuda, Hiroki Takami, Tomohisa Nomura, Manabu Sugita

Introduction

Lemborexant is a dual orexin receptor antagonist (DORA) with a favorable safety profile at therapeutic doses. However, clinical data regarding its toxic effects in overdose scenarios are limited. This is the first published case report of serially measured plasma concentrations of lemborexant in a patient who survived following acute overdose.

Case report

A 33-year-old woman presented to the emergency department four hours after ingesting an estimated 720 mg of lemborexant and 78 mg of eszopiclone. She exhibited mild central nervous system depression (Glasgow Coma Scale score 11) but was hemodynamically stable. With supportive care alone, the patient’s consciousness spontaneously improved. Retrospective analysis revealed that her plasma lemborexant concentration increased from 0.144 µg/mL at four hours to a peak of 1.410 µg/mL at nine hours post-ingestion, despite undergoing clinical recovery.

Discussions

This case suggests that massive lemborexant overdoses may not cause life-threatening toxicity even when plasma levels approach those reported in fatal cases. This case provides preliminary but clinically important data and highlights the need for further research to better characterize the clinical implications and management of lemborexant overdoses.

lemborexant是一种双重食欲素受体拮抗剂（DORA），在治疗剂量下具有良好的安全性。然而，关于其在过量情况下的毒性作用的临床数据有限。这是首次在急性用药过量后存活的患者中连续测量lemborexant血浆浓度的病例报告。病例报告：一名33岁妇女在摄入约720 毫克lemborexant和78 毫克eszopiclone四小时后到急诊室就诊。她表现出轻微的中枢神经系统抑郁（格拉斯哥昏迷评分11分），但血流动力学稳定。仅通过支持性护理，患者的意识自然得到改善。回顾性分析显示，她的血浆leborexant浓度从摄入后4小时的0.144 µg/mL增加到摄入后9小时的峰值1.410 µg/mL，尽管经过了临床恢复。本病例表明，即使血浆浓度接近致死病例所报告的水平，大量过量的香氛也可能不会造成危及生命的毒性。该病例提供了初步但临床上重要的数据，并强调了进一步研究的必要性，以更好地描述lemborexant过量的临床意义和管理。

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引用次数: 0

Amino alkyl-alkyl/aryl sulphides (DRDE-07 and analogues) as promising cytoprotectants for sulphur and nitrogen mustards – A review 氨基烷基-烷基/芳基硫化物（DRDE-07及类似物）作为硫、氮芥菜细胞保护剂的研究进展

Q1 Environmental Science

Toxicology Reports

Pub Date : 2025-12-01 DOI: 10.1016/j.toxrep.2025.102175

R. Vijayaraghavan , M. Sharma

Several antidotes and medical countermeasures were experimented for the protection of one of the notorious chemical warfare agents, the mustard gas, also known as sulphur mustard (SM). Among them, the DRDE series of compounds (amino alkyl-alkyl/aryl sulphides) showed good protection and safety in pre-clinical studies as a prophylactic antidote when administered orally. These compounds showed better protection compared to other experimented molecules, such as amifostine, N-acetylcysteine, melatonin, sodium thiosulphate, and flavonoids. Although many studies have focused on the DRDE-07 molecule, the structurally related DRDE-30 and DRDE-35 have shown better safety and protection. Among them, DRDE-30 showed the best protection for SM and nitrogen mustards, as well as against radiation, and also as a cytoprotectant for anticancer agents. In this review, all the published papers on the DRDE series of compounds are compiled and discussed, with the aim that if any one of these molecules is recommended as an oral prophylactic drug, further development would occur for a more effective, broad-spectrum cytoprotectant.

为保护一种臭名昭著的化学战剂芥子气（又称硫磺芥子气），试验了几种解毒剂和医疗对策。其中，DRDE系列化合物（氨基烷基-烷基/芳基硫化物）作为口服预防性解毒剂在临床前研究中表现出良好的保护作用和安全性。与其他实验分子，如氨磷汀、n -乙酰半胱氨酸、褪黑素、硫代硫酸钠和类黄酮相比，这些化合物显示出更好的保护作用。虽然许多研究集中在DRDE-07分子上，但结构相关的DRDE-30和DRDE-35显示出更好的安全性和保护作用。其中，DRDE-30对SM和氮芥的保护效果最好，对辐射的保护效果最好，也是抗癌药物的细胞保护剂。本文对已发表的关于DRDE系列化合物的所有论文进行了整理和讨论，目的是如果这些分子中的任何一种被推荐作为口服预防药物，将会进一步开发出更有效的广谱细胞保护剂。

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引用次数: 0

Corrigendum to "A case series of hyperthermia crisis in cough mixture ingestion: Why early cooling save lives" [Toxicol. Rep., 15 (2025) 102168]. 《咳合剂摄入引起的热休克系列病例：为什么早期降温可以挽救生命》的勘误表。众议员，15(2025)102168]。

Q1 Environmental Science

Toxicology Reports

Pub Date : 2025-12-01 DOI: 10.1016/j.toxrep.2025.102178

Hon Chun, Tin Yat Anthony Chow

[This corrects the article DOI: 10.1016/j.toxrep.2025.102168.].

[这更正了文章DOI: 10.1016/j.toxrep.2025.102168.]。

引用次数: 0