Toxicology Reports最新文献

Safety assessment of a proprietary fenugreek mucilage composition (FenuMat®): Acute and subchronic toxicity studies 专有胡芦巴黏液成分（FenuMat®）的安全性评估：急性和亚慢性毒性研究

Q1 Environmental Science

Toxicology Reports

Pub Date : 2026-06-01 Epub Date: 2025-12-18 DOI: 10.1016/j.toxrep.2025.102187

Megha Kelenchery Ganesh , Rani K. Cherian , Syam Das Sivadasan , Manu Aryan , Krishnakumar Illathu Madhavamenon

Fenugreek (Trigonella foenum-graecum) seeds and their extracts are popular culinary ingredients and nutraceuticals. The seed mucilage contains galactomannan, a soluble dietary fiber with prebiotic potential and divergent therapeutic effects. A proprietary fenugreek galactomannan preparation (F-GM), FenuMat®, functions as a natural self-emulsifying hydrogel, enhancing nutrient delivery and bioavailability. Although fenugreek seed safety is well documented, the safety evaluation of FenuMat® is warranted to ensure its compliance with regulatory standards. Hence, the present study evaluated the safety of FenuMat® in adult Wistar rats of both sexes, following OECD guidelines. In the acute oral toxicity study (14 days; OECD Guideline 423), no treatment related adversities were observed, indicating an LD₅₀ above 2000 mg/kg body weight. The subchronic toxicity study (OECD Guideline 408, repeated dose; 90 days) at doses of 250, 500 and 1000 mg/kg b.wt. revealed no significant alterations in hematological or biochemical parameters, or in food and water intake. However, significant reductions in serum glucose levels (at 500 mg/kg and 1000 mg/kg b.wt.) and LDL cholesterol levels (at 1000 mg/kg b.wt.) were observed. Histopathological evaluation revealed no morphological abnormalities in the major organs. Terminal autopsy revealed consistent relative organ weights and no treatment-related histopathological alterations. The high-dose recovery group (1000 mg/kg b.wt.) exhibited no mortality or adverse effects, with hematological and biochemical parameters comparable to controls, indicating a no-observed-adverse-effect level (NOAEL) of 1000 mg/kg b.wt. Further, the Ames test on four Salmonella triphimurium strains, with and without metabolic activation, demonstrated no mutagenic potential, indicating FenuMat®’s suitability for human use.

葫芦巴种子及其提取物是流行的烹饪原料和营养保健品。种子粘液含有半乳甘露聚糖，一种具有益生元潜力的可溶性膳食纤维和不同的治疗效果。一种专有的胡芦巴半乳甘露聚糖制剂（F-GM）， FenuMat®，作为一种天然的自乳化水凝胶，增强营养输送和生物利用度。虽然胡芦巴种子的安全性有很好的记录，但FenuMat®的安全性评估是有必要的，以确保其符合监管标准。因此，本研究按照经合组织的指导方针，评估了FenuMat®在成年Wistar大鼠中的安全性。在急性口服毒性研究（14天；OECD指南423）中，没有观察到与治疗相关的不良反应，表明LD₅0高于2000 mg/kg体重。亚慢性毒性研究（OECD指南408，重复给药；90天），剂量分别为250、500和1000 mg/kg b.wt。血液学或生化参数，食物和水的摄入量没有明显的改变。然而，观察到血清葡萄糖水平（500 mg/kg和1000 mg/kg b.wt.）和LDL胆固醇水平（1000 mg/kg b.wt.）显著降低。组织病理学检查未见主要脏器形态异常。晚期尸检显示相对器官重量一致，没有治疗相关的组织病理学改变。高剂量恢复组（1000 mg/kg b.wt.）未出现死亡率或不良反应，其血液学和生化参数与对照组相当，表明未观察到的不良反应水平（NOAEL）为1000 mg/kg b.wt.。此外，对四种三鼠沙门氏菌菌株进行的Ames试验，无论是否有代谢激活，均显示无致突变潜力，表明FenuMat®适合人类使用。

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引用次数: 0

Berberine nanoemulsion against nephrotoxicity induced by bisphenol a in rats during pre-puberty stage 小檗碱纳米乳对青春期前大鼠双酚a肾毒性的影响

Q1 Environmental Science

Toxicology Reports

Pub Date : 2026-06-01 Epub Date: 2026-01-08 DOI: 10.1016/j.toxrep.2026.102203

Shahnaz Rajabi , Atena Mansouri , Tahora Fakhrtaha , Parisa Sadighara , Fariborz Samini , Saeed Samarghandian , Tahereh Farkhondeh

This study evaluated the effects of berberine nanoemulsion (BNE) against nephrotoxicity induced by bisphenol A (BPA), a plastic chemical, in rats during the pre-puberty stage. Thirty-six male Wistar rats (23-day-old) were randomly allocated to six groups (n = 6): Group 1 (Control). Group 2 (BPA): BPA (200 mg/kg) and saline. Groups 3 (BNE 5) and 4 (BNE 10): BNE (5 and 10 mg/kg,). Groups 5 (BPA + BNE 5) and 6 (BPA + BNE 10): BPA with BNE (5 and 10 mg/kg). After 30 days, kidney samples were obtained for histopathological and biochemical tests. BPA increased serum urea, uric acid, creatinine (Cr), blood urea nitrogen (BUN), and kidney levels of malondialdehyde (MDA), nitric oxide (NO), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) versus controls. BPA decreased estimated glomerular filtration rate (eGFR), reduced glutathione (GSH), and superoxide dismutase (SOD) activity. BNE (10 mg/kg) reversed these changes to near-control levels. Histopathology showed lumen obliteration of renal tubules, dilated vessels, glomerular atrophy, and large capsular space in the BPA group. Less inflammation and improved glomerular architecture were seen in the BPA + BNE10 group. In conclusion, BNE (10 mg/kg) significantly alleviated BPA-induced oxidative stress, inflammation and histopathological changes in the kidney of rats during the pre-puberty stage due to its antioxidant and anti-inflammatory effects. This finding confirms the safety and efficacy of BNE in nephrotoxic model during pre-puberty stage. It can be suggested to investigate this agent in clinical study as a possible therapeutic approach.

本研究评估了小檗碱纳米乳（BNE）对青春期前大鼠双酚A (BPA)（一种塑料化学物质）引起的肾毒性的影响。选取23日龄雄性Wistar大鼠36只，随机分为6组（n = 6）：第一组（对照组）。第二组（BPA）： BPA（200 mg/kg）和生理盐水。3组（BNE 5）和4组（BNE 10）： BNE（5和10 mg/kg，）。第5组（BPA + BNE 5）和第6组（BPA + BNE 10）： BPA与BNE（5和10 mg/kg）。30 d后取肾标本进行组织病理学和生化检测。与对照组相比，BPA增加了血清尿素、尿酸、肌酐（Cr）、尿素氮（BUN）和肾脏丙二醛（MDA）、一氧化氮（NO）、白细胞介素-6 （IL-6）、白细胞介素-1β (IL-1β)和肿瘤坏死因子-α (TNF-α)的水平。BPA降低肾小球滤过率（eGFR）、还原型谷胱甘肽（GSH）和超氧化物歧化酶（SOD）活性。BNE（10 mg/kg）将这些变化逆转至接近控制水平。组织病理学显示BPA组肾小管管腔闭塞，血管扩张，肾小球萎缩，囊腔间隙大。BPA + BNE10组炎症减轻，肾小球结构改善。综上所述，BNE（10 mg/kg）通过抗氧化和抗炎作用，显著缓解bpa诱导的青春期前大鼠肾脏氧化应激、炎症和组织病理学改变。这一发现证实了BNE在青春期前期肾毒性模型中的安全性和有效性。建议在临床研究中探讨该药作为一种可能的治疗方法。

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引用次数: 0

Acute effect of tetracycline on systemic stress markers and organ histopathology in juvenile Nile tilapia, Oreochromis niloticus 四环素对尼罗罗非鱼幼鱼系统应激标志物和器官组织病理学的急性影响

Q1 Environmental Science

Toxicology Reports

Pub Date : 2026-06-01 Epub Date: 2026-02-03 DOI: 10.1016/j.toxrep.2026.102215

Md Al-Emran , Md Asad Ud Zahan Siddique , Md Sayem Sheikh , Md Ruhul Amin, Most Rifah Tamanna, Purabi Karmoker Puja, Kumari Bristi Rani, AKM Afzal Hossain, Md Abu Rahad, Md Shahjahan

Antibiotic contamination in aquaculture systems frequently encounter severe threat to aquatic life including fish. This study aimed to evaluate acute toxicological effects of tetracycline in juvenile Nile tilapia, Oreochromis niloticus. We exposed ten fish in each tank with nominal tetracycline concentration of 0 μg/L, 10 μg/L, 100 μg/L, 500 μg/L, 1000 μg/L, and 5000 μg/L, under semi-static condition for 96 h. After the exposure periods, six fish per treatment (n = 6) were sampled to evaluate blood glucose, hemoglobin, frequencies of erythrocyte cellular and nuclear abnormalities, and histopathology of gills, intestine, liver, and kidney. Tetracycline induced clear dose-dependent effects in studied fish. Blood glucose increased significantly (p < 0.05) from 100 μg/L and onward, indicating acute metabolic stress, whereas hemoglobin decreased significantly at 500 and 5000 μg/L indicating compromised oxygen transport. Erythrocyte cellular and nuclear abnormalities rose in a threshold manner; twin, tear-drop, elongated, binucleated cells and nuclear buds became significantly more frequent at ≥ 100 μg/L and intensified at higher doses. Gill pathology such as congestion, lamellar degeneration and fusion, epithelial hypertrophy/hyperplasia was appeared from medium doses and was most pronounced at 5000 μg/L. Significant reduction in villus length, vacuolation of enterocyte and fusion of brush-border of intestine was observed at 500 μg/L and higher doses. Liver lesions such as vacuolation, hemorrhage, melanomacrophase centers, and necrosis were intensified with doses. Besides, renal alterations such as mild glomerular expansion at 100 μg/L, dilation of Bowman’s space and tubular changes at 500 μg/L and above concentrations were observed. Our findings highlight sensitive early-warning biomarkers and underscore the need for chronic exposure studies and residual analysis for risk assessments of antibiotic usage in aquaculture.

水产养殖系统中的抗生素污染经常对包括鱼类在内的水生生物造成严重威胁。本研究旨在评价四环素对尼罗罗非鱼幼鱼的急性毒理学效应。在半静态条件下，以四环素标称浓度0、10、100、500、1000、5000 μg/L分别饲喂10尾鱼96 h。暴露期后，每次处理6条鱼（n = 6）取样，评估血糖、血红蛋白、红细胞细胞和核异常频率，以及鳃、肠、肝和肾的组织病理学。四环素在研究鱼类中诱导了明显的剂量依赖效应。从100 μg/L及以后，血糖显著升高（p <； 0.05），表明急性代谢应激，而血红蛋白在500和5000 μg/L时显著下降，表明氧运输受损。红细胞和细胞核异常呈阈值升高；≥ 100 μg/L时，双细胞、泪滴细胞、细长细胞、双核细胞和核芽出现频率显著增加，且随剂量增加而增强。中剂量时出现鳃部充血、板层退变融合、上皮肥大/增生等病变，在5000 μg/L时表现最为明显。500 μg/L及以上剂量组绒毛长度明显缩短，肠细胞空泡化，肠刷状缘融合。肝脏病变如空泡、出血、黑素巨期中心和坏死随剂量增加而加剧。此外，在100 μg/L及以上浓度下，观察到肾脏的改变，如轻度肾小球扩张、鲍曼间隙扩张和肾小管改变。我们的研究结果强调了敏感的早期预警生物标志物，并强调了对水产养殖中抗生素使用的风险评估进行慢性暴露研究和残留分析的必要性。

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引用次数: 0

Safety assessment and gastrointestinal tolerance of a novel highly bioavailable turmeric extract formulation: A randomised, double-blind, placebo controlled clinical trial 一种新型高生物利用度姜黄提取物配方的安全性评估和胃肠道耐受性：一项随机、双盲、安慰剂对照临床试验

Q1 Environmental Science

Toxicology Reports

Pub Date : 2026-06-01 Epub Date: 2025-11-29 DOI: 10.1016/j.toxrep.2025.102176

Julie Laval , Kirt R. Phipps , Sonia Brinet , Marie-Cécile Fournier , Benoit Douillard , Sa Pham , Alexandra Lobach , Severin Mueller , Pascale Fança-Berthon

Recent advances have led the development of turmeric formulations providing notable blood levels of curcuminoids following ingestion. However, there is a lack of clinical trials confirming the tolerability and safety of these formulations after repeated consumption by healthy subjects, as previous studies have primarily focused on efficacy and safety in subjects with health conditions. This randomised controlled trial assessed the gastrointestinal tolerance and safety of a novel turmeric extract formulation (TF) in healthy adults. Sixty subjects were assigned to either the TF group, receiving 1000 mg or placebo group (maltodextrin), once daily for 5 weeks. The study evaluated: gastrointestinal tolerance [including bloating, abdominal cramping, stomach noises, flatulence, frequency and consistency of stools and perception of Gastrointestinal Quality of Life (GIQLI)], a comprehensive analysis of haematology, clinical biochemistry and urinalysis parameters, vital signs, and a record of adverse events (AEs). No statistically significant differences were observed in gastrointestinal tolerance between the groups. Clinical parameters were not adversely affected by TF consumption, and the incidence and severity of AEs were similar in both groups. In conclusion, daily oral consumption of 1000 mg TF, thus exceeding the recommended 300 mg dose, was well tolerated and safe in healthy adults over the 5-week period.

最近的进展导致了姜黄配方的发展，在摄入后提供显着的姜黄素血液水平。然而，由于以前的研究主要集中在健康受试者的疗效和安全性上，缺乏临床试验来证实这些配方在健康受试者反复食用后的耐受性和安全性。这项随机对照试验评估了一种新型姜黄提取物配方（TF）在健康成人中的胃肠道耐受性和安全性。60名受试者被分配到TF组，接受1000 mg或安慰剂组（麦芽糊精），每天一次，持续5周。该研究评估了胃肠道耐受性[包括腹胀、腹部绞痛、胃噪音、胀气、大便频率和一致性以及胃肠道生活质量（GIQLI）的感知]、血液学、临床生化和尿液分析参数的综合分析、生命体征和不良事件（ae）记录。两组间胃肠耐受性无统计学差异。临床参数没有受到TF消耗的不利影响，两组ae的发生率和严重程度相似。综上所述，在5周的时间内，健康成人每日口服1000 mg TF，超过推荐剂量300 mg，耐受性良好且安全。

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引用次数: 0

Rutin outperforms gallic acid in mitigating carbon tetrachloride-induced nephrotoxicity: Integrated in silico (docking, MD simulations, DFT) and in vivo mechanistic validation 芦丁在减轻四氯化碳引起的肾毒性方面优于没食子酸：集成在硅（对接，MD模拟，DFT）和体内机制验证

Q1 Environmental Science

Toxicology Reports

Pub Date : 2026-06-01 Epub Date: 2026-02-02 DOI: 10.1016/j.toxrep.2026.102214

Hend A. Essa , Abdallah Ashraf , Mohamed Elsheikh

Background

Carbon tetrachloride (CCl₄) induces nephrotoxicity via oxidative stress and inflammation.

Aim

This novel comparative study evaluated the nephroprotective efficacy of rutin and gallic acid (GA) against CCl₄-induced kidney damage by elucidating their antioxidant and anti-inflammatory mechanisms.

Method

In silico, Quantum Mechanics/Molecular Mechanics methods screened rutin and GA's activity against Tumor Necrosis Factor (TNF) by inhibiting TNF-Alpha Convertase Enzyme (TACE) and Interleukin-6 (IL-6) via its receptor IL-6Rα, alongside assessing radical-neutralizing capacity. In vivo, twenty-four male Sprague-Dawley rats were divided into four groups (n = 6): normal control, CCl₄ (1 mL/kg, i.p., twice weekly), CCl₄ + rutin (40 mg/kg/day, oral), and CCl₄ + GA (40 mg/kg/day, oral) for four weeks. Renal function, oxidative stress, inflammation markers, histopathology, and immunohistochemistry were analyzed.

Results

In silico, rutin exhibited radical-neutralizing abilities and potential to inhibit TACE and IL-6Rα. GA showed divergence in molecular dynamics simulations for these targets and lower radical neutralization affinity, based on activation energy and reaction enthalpy. In vivo, CCl₄ induced nephrotoxicity, increasing kidney biomarkers, oxidative stress, and inflammatory markers. Both compounds significantly mitigated damage, reducing creatinine, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, urea, uric acid, lipid peroxidation, interleukin-6, tumor necrosis factor-α, p53, and NF-κB expression (p < 0.05). Antioxidant enzymes (reduced glutathione, glutathione S-transferase, superoxide dismutase, catalase) were enhanced. Rutin consistently demonstrated superior efficacy.

Conclusion

This first direct comparison confirms rutin’s superior efficacy over GA in mitigating CCl₄-induced nephrotoxicity via antioxidant and anti-inflammatory pathways. The integrated in silico and in vivo approach validates their mechanisms, highlighting rutin's prophylactic potential.

四氯化碳（CCl₄）通过氧化应激和炎症诱导肾毒性。目的探讨芦丁和没食子酸（GA）对CCl - 4诱导的肾损伤的抗氧化和抗炎作用机制。方法采用量子力学/分子力学方法筛选芦丁和GA对肿瘤坏死因子（TNF）的活性，通过其受体IL-6Rα抑制TNF- α转化酶（TACE）和白细胞介素-6 (IL-6)，同时评估自由基中和能力。在体内，24只雄性Sprague-Dawley大鼠分为4组（n = 6）：正常对照组、氯化钙（1 mL/kg，每日1次，每周2次）、氯化钙+ 芦丁（40 mg/kg/天，口服）、氯化钙+ GA（40 mg/kg/天，口服），连续4周。分析肾功能、氧化应激、炎症标志物、组织病理学和免疫组织化学。结果芦丁具有中和自由基的能力，有抑制TACE和IL-6Rα的潜力。基于活化能和反应焓，GA对这些靶点的分子动力学模拟存在差异，自由基中和亲和力较低。在体内，CCl 4诱导肾毒性，增加肾脏生物标志物、氧化应激和炎症标志物。这两种化合物都能显著减轻损伤，降低肌酐、肾损伤分子-1、中性粒细胞明胶酶相关的脂钙蛋白、尿素、尿酸、脂质过氧化、白细胞介素-6、肿瘤坏死因子-α、p53和NF-κB的表达（p <； 0.05）。抗氧化酶（还原性谷胱甘肽、谷胱甘肽s -转移酶、超氧化物歧化酶、过氧化氢酶）增强。芦丁一贯表现出优越的疗效。结论芦丁通过抗氧化和抗炎途径减轻CCl - 4所致肾毒性的作用优于GA。集成在硅和体内的方法验证了它们的机制，突出了芦丁的预防潜力。

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引用次数: 0

Acute polyneuropathy associated with Kambo poisoning: An unusual case report 急性多神经病变与康博中毒：一个不寻常的病例报告

Q1 Environmental Science

Toxicology Reports

Pub Date : 2026-06-01 Epub Date: 2026-01-05 DOI: 10.1016/j.toxrep.2026.102200

Julio César Mantilla-Pardo , Juan David García-Valencia , Juan Pablo Fernández-Cubillos

Kambo is a natural secretion obtained from the Amazonian frog Phyllomedusa bicolor, traditionally used in ritualistic and alternative medicine practices for its purported purifying and immunostimulatory effects. Acute intoxication has been associated with neuropsychiatric manifestations, electrolyte disturbances, and systemic complications; however, involvement of the peripheral nervous system has not been previously confirmed by electrodiagnostic studies. We report the case of a 40-year-old man with no prior medical history who developed rapidly progressive quadriparesis and facial diparesis four days after subcutaneous self-application of Kambo venom. Cerebrospinal fluid analysis demonstrated albuminocytologic dissociation, and nerve conduction studies revealed an acute demyelinating motor polyneuropathy with conduction block and preserved sensory conduction. Due to clinical deterioration and risk of respiratory failure, the patient required intensive care management. He initially underwent five sessions of plasmapheresis with limited improvement, followed by intravenous immunoglobulin at a dose of 0.4 g/kg/day for five days, resulting in partial neurological recovery. At three-month follow-up, he persisted with residual motor deficits without sensory involvement. This case represents, to our knowledge, the first electrodiagnostically confirmed report of acute polyneuropathy associated with Kambo poisoning. Clinicians should be aware that Kambo intoxication may extend beyond central neuropsychiatric effects to involve the peripheral nervous system, and early recognition with consideration of immunomodulatory therapy may be warranted.

Kambo是一种从亚马逊蛙Phyllomedusa bicolor中提取的天然分泌物，传统上用于仪式和替代医学实践，因为它具有据称的净化和免疫刺激作用。急性中毒与神经精神表现、电解质紊乱和全身并发症有关；然而，周围神经系统的受累尚未被先前的电诊断研究证实。我们报告的情况下，一个40岁的男子没有先前的病史，谁发展迅速进行性四肢瘫和面部重瘫的四天后，皮下自我应用坎博毒液。脑脊液分析显示白蛋白细胞分离，神经传导研究显示急性脱髓鞘运动多发性神经病伴传导阻滞和感觉传导保留。由于临床恶化和呼吸衰竭的风险，患者需要重症监护管理。他最初接受了5次血浆置换治疗，改善有限，随后静脉注射免疫球蛋白，剂量为0.4 g/kg/天，持续5天，导致神经系统部分恢复。在三个月的随访中，他仍然存在残余的运动缺陷，没有感觉受累。据我们所知，这是首例电诊断证实的与Kambo中毒相关的急性多神经病变报告。临床医生应该意识到Kambo中毒可能会超越中枢神经精神影响，涉及周围神经系统，并且考虑免疫调节治疗的早期识别可能是有保证的。

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引用次数: 0

Investigation of serum concentration and the type of opioid used in patients with opium poisoning 鸦片中毒患者血药浓度及阿片类药物类型调查。

Q1 Environmental Science

Toxicology Reports

Pub Date : 2026-06-01 Epub Date: 2026-01-31 DOI: 10.1016/j.toxrep.2026.102213

Armin Mansouri Sarabbadieh , Nazir Fattahi , Mohammad Mehdi Veisi , Afshin Almasi , Zahra Shaahmadi , Toraj Ahmadi Jouybari

Opioid poisoning constitutes a major public health issue in Iran and worldwide, with increasing rates attributed to both traditional opiates and synthetic derivatives such as methadone. Reliable assessment of serum opioid concentrations is essential for clinical management and prognosis. Quantitative measurement of serum opioid concentrations determines local epidemiological patterns and identifies risk factors that guide future prevention and treatment strategies. This descriptive cross-sectional study was conducted at Imam Khomeini Hospital in Kermanshah, Iran, from March to June 2023. Fifty adult patients with confirmed opioid poisoning were clinically diagnosed based on the classic opioid toxidrome (decreased consciousness, miotic pupils, and respiratory depression) documented at emergency department admission. Clinical diagnosis was confirmed by positive response to naloxone administration. Demographic and clinical data, type and route of opioid use, clinical features, laboratory results, and patient outcomes were recorded. Serum concentrations of opioids were measured using gas chromatography–mass spectrometry (GC–MS) after administration of antidotes. Statistical analysis was performed with SPSS 26, using a significance threshold of p < 0.05. Among 50 patients (86 % male, mean age 33.5 ± 9.8 years), methadone was the most common cause of poisoning (72 %), followed by opium and heroin. The principal clinical findings included apnea (44 %), miosis (44 %), and weakness/lethargy (38 %), with severe symptoms observed primarily in methadone cases. Serum methadone concentrations were significantly higher in men than women (p = 0.007), and in rural residents compared to urban (p = 0.005). Higher opioid serum levels were associated with more severe clinical presentations and increased need for intensive care. Most patients recovered with medical management; no in-hospital deaths occurred. Methadone has become the leading cause of opioid poisoning in this region, with high serum concentrations predicting increased clinical severity. Measurement of serum opioid levels is a valuable tool for risk stratification and should be integrated into standard management protocols. Attention must be given to both preventive education and tighter regulation of methadone distribution, particularly among high-risk groups.

类阿片中毒是伊朗和世界范围内的一个重大公共卫生问题，由于传统阿片类药物和美沙酮等合成衍生物，中毒率不断上升。可靠的血清阿片类药物浓度评估对临床管理和预后至关重要。血清阿片类药物浓度的定量测量确定了当地流行病学模式，并确定了指导未来预防和治疗战略的危险因素。这项描述性横断面研究于2023年3月至6月在伊朗克尔曼沙阿的伊玛目霍梅尼医院进行。50例确诊为阿片类药物中毒的成年患者在急诊科就诊时，根据典型的阿片类药物中毒症状（意识下降、瞳孔缩小和呼吸抑制）进行临床诊断。对纳洛酮治疗有积极反应，证实临床诊断。记录了人口统计学和临床数据、阿片类药物使用类型和途径、临床特征、实验室结果和患者结局。用气相色谱-质谱联用（GC-MS）法测定给药后血清阿片类药物浓度。采用SPSS 26进行统计学分析，显著性阈值为p

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引用次数: 0

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 : 2026-06-01 Epub 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

A meta-analysis on particulate matter-associated heavy metals in rural air: Concentration, seasonal variability, and pollution sources 农村空气中与颗粒物相关的重金属的荟萃分析：浓度、季节变化和污染源

Q1 Environmental Science

Toxicology Reports

Pub Date : 2026-06-01 Epub Date: 2025-12-23 DOI: 10.1016/j.toxrep.2025.102194

Majid Farhadi , Behrouz Beiranvand

Heavy metals (HMs) bonded to PM (Particulate Matter) are a significant component of rural air pollution. They're primarily released from fossil fuel combustion and the operational decay of automobiles, leading to their considerable presence in roadway dust. This study aims to examine the concentration and seasonal effects on HM emissions in rural air. The pooled mean concentrations for As (7.81 ng m^-³), Cd (4.42 ng m^-³), and Pb (60.97 ng m^-³) were statistically significant. Pb concentrations were exceptionally high in some rural areas of China, with mean values over 500 ng m^-³ reported in two studies. Studies showed notably high levels of Pb, Cu, and Zn, with some sites having exceptional concentrations. The analysis also found significant seasonal variations, with many HMs showing higher concentrations in winter, which is likely due to increased coal combustion for heating. Seasonal analysis in China revealed higher concentrations of several HMs in winter, likely due to increased coal combustion for heating. In spring, road and soil dust from natural phenomena such as dust storms was a primary source of HMs.

与颗粒物（PM）结合的重金属（HMs）是农村空气污染的重要组成部分。它们主要从化石燃料燃烧和汽车的运行衰变中释放出来，导致它们在道路灰尘中大量存在。本研究旨在探讨农村空气中HM排放的浓度和季节效应。砷（7.81 ng m-³）、镉（4.42 ng m-³）和铅（60.97 ng m-³）的混合平均浓度具有统计学意义。中国一些农村地区的铅浓度异常高，两项研究报告的平均值超过500 ng m-³。研究表明，铅、铜和锌的含量明显偏高，有些地方的浓度异常。分析还发现了显著的季节变化，许多HMs在冬季浓度较高，这可能是由于取暖用煤燃烧增加。中国的季节分析显示，几种HMs的浓度在冬季较高，可能是由于取暖用煤燃烧增加。在春季，沙尘暴等自然现象产生的道路和土壤粉尘是HMs的主要来源。

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引用次数: 0

Toxicological safety profiling of Berberis vulgaris hydroethanolic extract using rodent, zebrafish, and in silico models 用啮齿动物、斑马鱼和计算机模型研究小檗水乙醇提取物的毒理学安全性

Q1 Environmental Science

Toxicology Reports

Pub Date : 2026-06-01 Epub Date: 2025-12-23 DOI: 10.1016/j.toxrep.2025.102195

Abanti Goswami , Vara Prasad Saka , Mahima Sharma , Narasimha Kumar G.V. , Pankaj Gupta , Digvijay Verma , Subhash Kaushik

Background

The hydroethanolic extract of Berberis vulgaris root bark (BV) is extensively used in traditional medicine, particularly Homoeopathy, for treating renal and hepatic disorders, yet a systematic safety evaluation remains limited.

Objectives

This study aimed to establish a comprehensive preclinical safety profile of BV using in vivo rodent and zebrafish models, alongside in silico toxicity predictions.

Methods

Phytochemical profiling was conducted using Liquid Chromatography–Mass Spectrometry (LC–MS). Acute and 28-day repeated-dose oral toxicity studies were performed in Wistar rats following OECD guidelines 423 and 407, respectively. Developmental toxicity was assessed in zebrafish embryos (OECD 236), and in silico toxicity predictions for identified phytoconstituents were generated using ProTox 3.0.

Results

LC-MS analysis identified 22 bioactive chemical components. In the acute oral toxicity study, BV administered at 2000 µL/kg caused no mortality or toxicity, indicating an LD₅₀ > 2000 µL/kg. The 28-day repeated-dose study showed no significant alterations in haematological, biochemical, or histological parameters at doses up to 1000 µL/kg/day, establishing a No Observed Adverse Effect Level (NOAEL) of ≥ 1000 µL/kg/day. While lower concentrations were safe in zebrafish, high concentrations (4 µL/2 ml) induced developmental abnormalities such as scoliosis and pericardial edema. Computational analysis predicted low-to-moderate toxicity for the majority of phytoconstituents.

Conclusion

BV exhibits a wide safety margin in rodent models and is non-toxic at therapeutically relevant doses. However, observed developmental effects in zebrafish suggest caution at high concentrations, supporting the need for adherence to recommended dosages in traditional therapeutic contexts.

小檗（Berberis vulgaris）根皮（BV）的氢乙醇提取物被广泛用于传统医学，特别是顺势疗法，用于治疗肾脏和肝脏疾病，但系统的安全性评估仍然有限。本研究旨在通过啮齿动物和斑马鱼体内模型，以及硅毒性预测，建立BV的全面临床前安全性。方法采用液相色谱-质谱法（LC-MS）进行植物化学分析。分别按照OECD指南423和407对Wistar大鼠进行了急性和28天重复剂量口服毒性研究。对斑马鱼胚胎的发育毒性进行了评估（OECD 236），并使用ProTox 3.0对鉴定的植物成分进行了硅毒性预测。结果液相色谱-质谱分析鉴定出22种生物活性成分。在急性口服毒性研究中，给予2000 μ L/kg的BV没有造成死亡或毒性，表明LD₅₀>； 2000 μ L/kg。这项为期28天的重复给药研究显示，当剂量高达1000 µL/kg/天时，血液学、生化或组织学参数没有显著改变，建立了≥ 1000 µL/kg/天的未观察到不良反应水平（NOAEL）。虽然低浓度在斑马鱼中是安全的，但高浓度（4 µL/2 ml）会引起发育异常，如脊柱侧凸和心包水肿。计算分析预测大多数植物成分具有中低毒性。结论bv在啮齿类动物模型中具有较宽的安全范围，且在治疗相关剂量下无毒。然而，在斑马鱼中观察到的发育影响表明，高浓度时要谨慎，这支持了在传统治疗背景下坚持推荐剂量的必要性。

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引用次数: 0