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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 Pub 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 Pub 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
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 Pub 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
Clinical evaluation of oral fluid point-of-care testing for drugs of abuse compared to urinary point-of-care testing at a large-scale music festival 大型音乐节上口服液即时检测与尿液即时检测对滥用药物的临床评价
Q1 Environmental Science Pub Date : 2025-12-18 DOI: 10.1016/j.toxrep.2025.102192
Frantzen MGM , Gresnigt FMJ , Litsenburg van RTH , Franssen EJF

Background

Urinary point-of-care testing for recreational drugs is commonly used in clinical settings. An oral fluid-based point-of-care test is a less invasive alternative, but the reliability and clinical applicability in a real-life acute care setting is unclear.

Aim

To assess the concordance of oral fluid point-of-care testing compared to urine point-of-care testing for recreational drugs in a prehospital clinical setting.

Methods

This study was conducted during a large-scale dance music festival in October 2023. Urine and oral fluid samples were collected at the event medical station from volunteers with a suspected drug intoxication. Participants aged 18 years and older were included if both samples were provided and at least one substance tested positive. The percentage of positive oral fluid test results per recreational drug were compared with those of the urine point-of-care test.

Results

A total of 78 patients were included. For most drug substances, positivity rates were similar between the two test types. Methamphetamine/3,4-methylenedioxymethamphetamine was the only substance that showed significantly more positive results in oral fluid compared to urine (p < 0.001). For all other substances, the differences between the two tests were small, with slightly higher positivity rates (on average 3.9 %) detected in oral fluid.

Conclusion

Oral fluid point-of-care testing shows potential in specific scenarios but requires further validation. It is a less invasive alternative to urine point-of-care testing for recreational drugs in a clinical setting. Nevertheless, it is important to consider the differences in test characteristics, such as detection window. Further research is needed to evaluate the reliability in other populations and settings.
背景:在临床环境中,日常护理点检测娱乐性药物是常用的。基于口腔液体的即时检测是一种侵入性较小的替代方法,但其在现实生活中的急性护理环境中的可靠性和临床适用性尚不清楚。目的评价院前临床环境中口服液体护理点检测与尿液护理点检测娱乐性药物的一致性。方法本研究在2023年10月的大型舞蹈音乐节期间进行。在事件医疗站收集了疑似药物中毒志愿者的尿液和口服液样本。如果提供了两个样本,并且至少有一种物质检测呈阳性,则包括18岁及以上的参与者。将每种娱乐性药物的口服液检测结果阳性的百分比与尿液即时检测结果阳性的百分比进行比较。结果共纳入78例患者。对于大多数原料药,两种检测类型的阳性率相似。甲基苯丙胺/3,4-亚甲基二氧基甲基苯丙胺是唯一在口腔液中比在尿液中显示更多阳性结果的物质(p <; 0.001)。对于所有其他物质,两种测试之间的差异很小,在口腔液中检测到的阳性率略高(平均为3.9 %)。结论口服液点护理测试在特定情况下具有潜力,但需要进一步验证。在临床环境中,它是一种侵入性较小的替代尿样即时检测娱乐性药物的方法。然而,重要的是要考虑测试特性的差异,例如检测窗口。需要进一步的研究来评估在其他人群和环境中的可靠性。
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引用次数: 0
Investigation of alpha smooth muscle actin changes in the liver of cholestatic rats following the consumption of L-theanine 摄入l -茶氨酸后,胆汁沉积大鼠肝脏α -平滑肌肌动蛋白变化的研究
Q1 Environmental Science Pub Date : 2025-12-18 DOI: 10.1016/j.toxrep.2025.102193
Mobina Daneshnia , Pejman Mortazavi , Mahsa Ale-Ebrahim , Razieh Hosseini
Cholestatic liver disease represents a major global health threat, resulting in significant morbidity and mortality. Cholestasis can be induced in laboratory animals using Bile Duct Ligation (BDL) technique. Activated Hepatic Stellate Cells (aHSCs) express Alpha Smooth Muscle Actin (α-SMA), which is correlated with experimental liver fibrogenesis. The Camellia sinensis plant produces L-Theanine, an amino acid (AA), in its roots. This research endeavored to conduct a comprehensive assessment of the anti-fibrotic effects of L-Theanine alongside α-SMA changes in the liver of cholestatic rats. Rats were classified into eight experimental groups, each consisting of five animals, including; (1) normal control group, (2) BDL control group, (3–5) healthy experimental groups, 6–8) BDL + L-Theanine groups. L-Theanine solution (100, 200 or 400 mg kg−1) was administered to the animals by Intragastric gavage (once a day) for 30 successive days. BDL significantly elevated the enzymatic activity of Gamma-glutamyl transferase (GGT), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Aspartate aminotransferase (AST) and elevated the amount of total bilirubin. These biochemical alterations were ameliorated when L-Theanine was administered. Masson`s Trichrome and Immunohistochemical (IHC) staining revealed that BDL expanded the collagen deposition and α-SMA expression in hepatic tissue. Administration of L-Theanine, remarkably alleviated these alterations. L-Theanine attenuates hepatic fibrosis through decreasing the production of α-SMA.
胆汁淤积性肝病是一个主要的全球健康威胁,导致大量发病率和死亡率。胆管结扎(BDL)技术可诱导实验动物胆汁淤积。活化的肝星状细胞(aHSCs)表达α-平滑肌肌动蛋白(α-SMA),其与实验性肝纤维化有关。山茶植物在其根部产生l -茶氨酸,一种氨基酸(AA)。本研究旨在综合评价l -茶氨酸对胆汁淤积大鼠肝脏α-SMA变化的抗纤维化作用。将大鼠分为8个实验组,每组5只,包括;(1)正常对照组,(2)BDL对照组,(3-5)健康实验组,(6-8)BDL + l -茶氨酸组。l -茶氨酸溶液(100、200或400 mg kg−1)灌胃给药(每天1次),连续30天。BDL显著提高了γ -谷氨酰转移酶(GGT)、丙氨酸转氨酶(ALT)、碱性磷酸酶(ALP)、天冬氨酸转氨酶(AST)活性,提高了总胆红素水平。当给予l -茶氨酸时,这些生化改变得到改善。马氏三色和免疫组化(IHC)染色显示BDL增加了肝组织中胶原沉积和α-SMA的表达。l -茶氨酸可显著减轻这些变化。l -茶氨酸通过减少α-SMA的产生来减轻肝纤维化。
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引用次数: 0
Concomitant food intake markedly alters plasma glutamic acid kinetics after oral monosodium glutamate administration in rats: Relevance to dietary safety evaluation 大鼠口服谷氨酸钠后,伴食显著改变血浆谷氨酸动力学:与饮食安全性评价相关
Q1 Environmental Science Pub Date : 2025-12-16 DOI: 10.1016/j.toxrep.2025.102191
Ryosei Sakai, Risa Motoi, Yusuke Amino, Kohsuke Hayamizu

Background

Monosodium glutamate (MSG) is widely used as a flavor enhancer and has been evaluated as safe by international authorities. However, some toxicological studies have employed oral bolus dosing of MSG without food, an approach that is unlikely to reflect physiological dietary exposure.

Objectives

To determine how concomitant food intake modifies plasma glutamic acid kinetics following oral MSG administration in rats, thereby improving the interpretation of toxicological data.

Methods

Male Wistar rats received graded oral doses of MSG (150, 300, or 600 mg/kg) with or without a liquid diet (Sustagen®). Plasma glutamic acid concentrations were measured by LC-MS/MS, and pharmacokinetic parameters were determined.

Results

Bolus MSG administration alone caused rapid, dose-dependent increases in plasma glutamic acid, with peak concentrations occurring 20–30 min post-dose. Co-administration of Sustagen® markedly reduced both Cmax and AUC and also delayed Tmax, indicating that food intake substantially attenuated systemic glutamic acid exposure.

Conclusions

Concomitant food intake profoundly alters plasma glutamic acid kinetics after oral MSG administration in rats. These findings emphasize the importance of considering realistic dietary exposure conditions when interpreting toxicological studies of MSG and related glutamate salts and underscore the need for physiologically relevant dosing regimens.
摘要谷氨酸钠(MSG)作为一种风味增强剂被广泛使用,并被国际权威机构评价为安全的。然而,一些毒理学研究采用了不含食物的口服MSG,这种方法不太可能反映生理饮食暴露。目的探讨大鼠口服味精后伴食对血浆谷氨酸动力学的影响,从而改进毒理学资料的解释。方法雄性Wistar大鼠分次口服味精(150、300或600 mg/kg),并给予或不给予液体饮食(Sustagen®)。采用LC-MS/MS法测定血清谷氨酸浓度,并测定药动学参数。结果单独给药味精引起血浆谷氨酸快速、剂量依赖性增加,在给药后20-30 min出现峰值浓度。联合使用Sustagen®显著降低了Cmax和AUC,并延迟了Tmax,表明食物摄入大大减少了系统性谷氨酸暴露。结论大鼠口服味精后,伴食可显著改变血浆谷氨酸动力学。这些发现强调了在解释味精和相关谷氨酸盐的毒理学研究时考虑实际饮食暴露条件的重要性,并强调了与生理相关的给药方案的必要性。
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引用次数: 0
Assessing aflatoxin exposure risk from imported nuts in the Jordan market 评估约旦市场进口坚果的黄曲霉毒素暴露风险
Q1 Environmental Science Pub Date : 2025-12-16 DOI: 10.1016/j.toxrep.2025.102190
Abdalmajeed M. Alajlouni , Dima Alkadri , Mohammad S. Abu-Hardan , Amer A. Al-Sakaji
This study assessed the contamination levels and health risk of aflatoxins in nuts from the markets in Jordan. A total of 180 nut samples (pistachios, almonds, walnuts, and cashews) were analyzed using high-performance liquid chromatography (HPLC) following immunoaffinity column clean-up and QuEChERS extraction. Aflatoxins were detected in 13 % of the samples, with pistachios showing the highest contamination rate. The Estimated Daily Intake (EDI) and Margin of Exposure (MOE) were calculated using deterministic risk assessment methods, based on the mean contamination levels and average nut consumption patterns in Jordan. All MOE values were below the safety threshold of 10,000, indicating a potential health risk. These findings emphasize the need for strengthened monitoring programs and regulatory actions to ensure food safety and minimize the public health risk.
本研究评估了约旦市场上坚果中黄曲霉毒素的污染水平和健康风险。采用高效液相色谱法(HPLC)对180份坚果样品(开心果、杏仁、核桃和腰果)进行了免疫亲和柱净化和QuEChERS提取。在13 %的样品中检测到黄曲霉毒素,其中开心果的污染率最高。根据约旦的平均污染水平和平均坚果消费模式,使用确定性风险评估方法计算估计每日摄入量(EDI)和暴露边际(MOE)。所有的MOE值都低于安全阈值10,000,表明存在潜在的健康风险。这些发现强调了加强监测计划和监管行动的必要性,以确保食品安全并将公共健康风险降至最低。
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引用次数: 0
Human fluoroacetate poisoning: A case series of 36 patients in Vietnam 人类氟乙酸中毒:越南36例患者的系列病例
Q1 Environmental Science Pub Date : 2025-12-14 DOI: 10.1016/j.toxrep.2025.102189
Nguyen Dang Duc , Lam Nguyen Hong Anh , Lam Nguyen Hong Khanh , Nguyen Dang Bach
Fluoroacetate poisoning is a rare but potentially lethal condition. We retrospectively reviewed 36 consecutive patients (27 males and 9 females) with confirmed poisoning treated at the Poison Control Center, Bach Mai Hospital, Hanoi, Vietnam, from June 2023 to December 2024. The mean age was 35.4 ± 12.6 years. The median time from ingestion to hospital admission was 3.5 h. On admission, 69.4 % of patients were asymptomatic, 22.2 % had seizures, and 8.3 % presented with altered consciousness. The mean Glasgow Coma Scale (GCS) score was 13.9 ± 2.0 (range 5–15). Median serum creatinine and creatine kinase (CK) levels were 72 µmol/L and 155 U/L, respectively; 16.7 % of patients had CK > 1000 U/L. Median ionized calcium was 1.015 mmol/L, and 19.4 % had serum lactate ≥ 2 mmol/L. Gastric lavage and activated charcoal were administered in 44.4 % and 36.1 % of cases, respectively. Six patients (16.7 %) required intensive care unit (ICU) admission, and no deaths occurred. Overall, most patients presented early with mild manifestations and had favorable short-term outcomes under supportive management.
氟乙酸中毒是一种罕见但可能致命的疾病。我们回顾性回顾了2023年6月至2024年12月在越南河内巴赫迈医院中毒控制中心治疗的36例确诊中毒患者(27男9女)。平均年龄35.4 ± 12.6岁。从摄入到入院的中位时间为3.5 h。入院时,69.4% %的患者无症状,22.2% %的患者有癫痫发作,8.3 %的患者表现为意识改变。格拉斯哥昏迷评分(GCS)平均评分为13.9 ± 2.0(范围5-15)。血清肌酐和肌酸激酶(CK)水平中位数分别为72µmol/L和155 U/L;16.7 %患者CK >; 1000 U/L。中位离子钙为1.015 mmol/L, 19.4 %血清乳酸≥ 2 mmol/L。洗胃和活性炭分别占44.4% %和36.1% %。6例患者(16.7 %)需要入住重症监护病房(ICU),无死亡发生。总体而言,大多数患者早期表现轻微,在支持性治疗下短期预后良好。
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引用次数: 0
Prenatal diazepam exposure impairs maternal caregiving behaviors in rats: Roles of GABAARα1 downregulation, serotonin depletion, and corticosterone dysregulation 产前地西泮暴露损害大鼠母性照料行为:GABAARα1下调、血清素耗竭和皮质酮失调的作用
Q1 Environmental Science Pub Date : 2025-12-13 DOI: 10.1016/j.toxrep.2025.102186
Yasaman Moin , Samira Khayat , Hamed Fanaei
This study investigated effects of prenatal exposure to diazepam on maternal and caregiving behaviors in rats postpartum.Twenty-four female rats were randomly divided into two groups: diazepam group and control group. Diazepam was administered during, and maternal behaviors were observed and recorded after delivery. Serum corticosterone levels during pregnancy, GABAARα1 expression, and serotonin and BDNF concentrations were measured in hippocampus and prefrontal cortex of the dams. The results showed that mothers exposed to diazepam exhibited a significant reduction in self-grooming (p = 0.0016), nursing (p < 0.0001), and nest-building behaviors (p < 0.0001) compared to the control group. Additionally, diazepam group showed fewer instances of pup retrieval (p = 0.0032) and licking (p = 0.0019). A significant increase in the latency to retrieve pups was observed in the diazepam group (p < 0.0001). The findings demonstrate a significant decrease in GABAARα1 mRNA expression within the prefrontal cortex (P = 0.0023) and hippocampus (P = 0.0138) of diazepam-treated group compared to the control group. Dams in the diazepam group exhibited significantly lower serum corticosterone levels at gestational day 20 (p = 0.0288) and postnatal day 1 (p = 0.0009) compared to the control group. Additionally, serotonin concentration in the prefrontal cortex (p = 0.0036) was significantly reduced in the diazepam group relative to controls.The present study demonstrated that prenatal diazepam exposure significantly impaired maternal caregiving behaviors in rats. These behavioral deficits were associated with disrupted serum corticosterone levels, diminished prefrontal serotonin concentrations, and reduced GABAARα1 mRNA expression in the prefrontal cortex and hippocampus. The findings suggest that diazepam interferes with neurochemical pathways critical for maternal motivation, potentially weakening maternal-infant bonding.
本研究探讨了产前接触地西泮对大鼠产后母性和照料行为的影响。雌性大鼠24只,随机分为安定组和对照组。分娩期间给予安定,分娩后观察记录产妇行为。测定妊娠期大鼠海马和前额皮质血清皮质酮水平、GABAARα1表达、血清素和BDNF浓度。结果显示,与对照组相比,暴露于地西泮的母亲在自我梳理(p = 0.0016)、护理(p <; 0.0001)和筑巢行为(p <; 0.0001)方面显着减少。此外,地西泮组检索幼犬(p = 0.0032)和舔幼犬(p = 0.0019)的次数较少。地西泮组找回幼崽的潜伏期显著增加(p <; 0.0001)。结果表明,与对照组相比,地西泮治疗组脑前额叶皮层(P = 0.0023)和海马(P = 0.0138)GABAARα1 mRNA表达显著降低。与对照组相比,地西泮组在妊娠第20天(p = 0.0288)和产后第1天(p = 0.0009)血清皮质酮水平显著降低。此外,与对照组相比,地西泮组前额叶皮层血清素浓度(p = 0.0036)显著降低。本研究表明,大鼠产前暴露于地西泮会显著损害母鼠的照料行为。这些行为缺陷与血清皮质酮水平紊乱、前额叶血清素浓度降低以及前额叶皮层和海马中GABAARα1 mRNA表达减少有关。研究结果表明,地西泮干扰了对母亲动机至关重要的神经化学通路,潜在地削弱了母婴关系。
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引用次数: 0
Synthesis, characterization, and anticancer evaluation of N-Heterocyclic entities: ADME profiling and In Silico predictions n -杂环实体的合成、表征和抗癌评价:ADME分析和硅预测
Q1 Environmental Science Pub Date : 2025-12-11 DOI: 10.1016/j.toxrep.2025.102184
Zakariae Abbaoui , Oussama Khibech , Hüseyin Karci , Muhammed Dündar , İlknur Özdemir , Nevin Gürbüz , Ahmet Koç , Wilson Agerico Dino , İsmail Özdemir , Naifa Alenazi , Rachid Touzani , Hanan Alghibiwi
This study aimed to synthesize a novel series of N-heterocyclic compounds and evaluate their integrated pharmacological potential by coupling in vitro selective cytotoxicity on tumor and normal cell lines with predictive in silico ADME-Tox profiling. This research highlights the anti-cancer potential of twelve synthesized compounds, five of which are new chemical entities never before described in the literature. Their detailed structural characterization (NMR 1H, 13C, IR), combined with in silico predictions (ADME-Tox), confirmed their ability to cross essential biological barriers, in particular the intestinal membrane and, for certain derivatives, the BBB. Biological evaluations conducted on SH-SY5Y (neuroblastoma) and HCT116 (colorectal carcinoma) cell lines revealed several compounds with IC50 values lower than those of cisplatin while exhibiting reduced cytotoxicity towards the normal human epithelial BEAS-2B cell line. In particular, the compound (1H-imidazol-1-yl)methanol (designated as Compound 6) stands out with IC50 values of 6.97 ± 0.06 µM on SH-SY5Y and 10.70 ± 0.33 µM on HCT116, significantly lower than those of cisplatin under the same experimental conditions. This profile, combined with virtually no toxicity on normal BEAS-2B cells (IC50 > 800 µM), highlights its remarkable selectivity. These results highlight optimized pharmacological properties and suggest the potential for developing selective therapeutic agents against different types of cancer, particularly neuronal and colorectal tumors. Future research will focus on in-depth mechanistic studies and in vivo validation to optimize the efficacy, pharmacokinetics, and safety of these promising molecules.
本研究旨在合成一系列新的n -杂环化合物,并通过对肿瘤和正常细胞系的体外选择性细胞毒性与预测硅ADME-Tox谱结合来评估其综合药理潜力。这项研究强调了12种合成化合物的抗癌潜力,其中5种是以前从未在文献中描述过的新化学实体。它们的详细结构表征(NMR 1H, 13C, IR),结合计算机预测(ADME-Tox),证实了它们跨越基本生物屏障的能力,特别是肠膜和某些衍生物血脑屏障。对SH-SY5Y(神经母细胞瘤)和HCT116(结直肠癌)细胞系进行的生物学评价显示,几种化合物的IC50值低于顺铂,但对正常人上皮BEAS-2B细胞系的细胞毒性降低。特别是化合物(1h -咪唑-1-酰基)甲醇(称为化合物6)在SH-SY5Y上的IC50值为6.97 ± 0.06 µM,在HCT116上的IC50值为10.70 ± 0.33 µM,明显低于相同实验条件下顺铂的IC50值。这一特征,结合对正常BEAS-2B细胞几乎没有毒性(IC50 > 800 µM),突出了其显著的选择性。这些结果突出了优化的药理学特性,并表明开发针对不同类型癌症的选择性治疗药物的潜力,特别是神经元和结直肠肿瘤。未来的研究将集中在深入的机制研究和体内验证,以优化这些有前途的分子的疗效、药代动力学和安全性。
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Toxicology Reports
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