Toxicology letters最新文献_第6页

DBDPE inhibits myogenic differentiation of C2C12 cells through inhibiting mitochondrial function and PI3K/AKT/mTOR signaling pathway DBDPE通过抑制线粒体功能和PI3K/AKT/mTOR信号通路抑制C2C12细胞的成肌分化

IF 2.9 3区医学 Q2 TOXICOLOGY

Toxicology letters

Pub Date : 2025-12-01 DOI: 10.1016/j.toxlet.2025.111783

Xinfang Tan , Jinglan Li , Yang Peng , Guoli Huang , Lijuan Yu , Guocheng Hu , Liangliang Xu

In recent years, decabromodiphenyl ethane (DBDPE), a type of brominated flame retardant, has gained popularity in industry as an alternative to decabromodiphenyl ether (BDEs). However, DBDPE exposure poses environmental pollution and primarily impacts muscle contraction and the reproductive endocrine system. The cellular implications and underlying mechanisms of DBDPE's effects on muscle remain poorly understood. In the present study, we investigated the effect of DBDPE on myoblast differentiation, apoptosis, as well as the potential mechanisms involved. The results demonstrated that exposure to DBDPE disrupted the differentiation of myotubes, inhibited cell proliferation, and increased levels of reactive oxygen species (ROS), ultimately leading to cell death. In addition, the RNAseq analysis revealed that DBDPE mainly affected the biological processes in mitochondria related to oxidative phosphorylation, ATP synthesis coupled electron transport, etc. Then we demonstrated that DBDPE inhibited mitochondrial membrane potential and ATP production, implying DBDPE resulted in mitochondrial dysfunction in C2C12 cells. Mechanistically, we showed that PI3K/AKT/mTOR signaling pathway was inhibited by DBDPE in C2C12 cells. And the apoptosis rate was significantly increased by DBDPE as demonstrated by increased active caspase-3 and TUNEL signal. Taken together, these findings suggest that low-dose exposure to DBDPE hampers myogenic differentiation and mitochondrial function, and increased cellular apoptosis through PI3K/AKT/mTOR signaling pathway, providing important insights for understanding its environmental toxic effects and conducting risk assessments.

近年来，十溴二苯乙烷（DBDPE）作为十溴二苯醚（BDEs）的替代品在工业上得到了广泛的应用。然而，DBDPE暴露会造成环境污染，主要影响肌肉收缩和生殖内分泌系统。DBDPE对肌肉影响的细胞意义和潜在机制仍然知之甚少。在本研究中，我们研究了DBDPE对成肌细胞分化、凋亡的影响及其可能的机制。结果表明，暴露于DBDPE破坏了肌管的分化，抑制了细胞增殖，增加了活性氧（ROS）水平，最终导致细胞死亡。此外，RNAseq分析显示DBDPE主要影响线粒体中氧化磷酸化、ATP合成耦合电子传递等生物过程。然后我们证明了DBDPE抑制线粒体膜电位和ATP的产生，这意味着DBDPE导致C2C12细胞的线粒体功能障碍。在机制上，我们发现DBDPE在C2C12细胞中抑制PI3K/AKT/mTOR信号通路。DBDPE可显著提高细胞凋亡率，活性caspase-3和TUNEL信号增加。综上所述，这些研究结果表明，低剂量暴露于DBDPE会阻碍肌源性分化和线粒体功能，并通过PI3K/AKT/mTOR信号通路增加细胞凋亡，为了解其环境毒性作用和进行风险评估提供了重要见解。

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引用次数: 0

Microbiological toxicology of the new antibiotic aditoprim on human intestinal microbiota 新型抗生素aditoprim对人肠道菌群的微生物毒理学研究。

IF 2.9 3区医学 Q2 TOXICOLOGY

Toxicology letters

Pub Date : 2025-12-01 DOI: 10.1016/j.toxlet.2025.111780

Junhao Wang , Chunbei Liu , Fangtong Gu , Yufeng Gu , Haihong Hao

Aditoprim (ADP) is a novel dihydrofolate reductase inhibitor. It has potent antibacterial activity, low toxicity, and no mutagenicity. These characteristics position it as a promising candidate for further research in clinical veterinary medicine and its effect on humans. Therefore, this research aimed to investigate the impact of ADP on human microbiota. ADP (0, 1, 16, and 128 mg/L) was added to chemostats containing human intestinal flora. Microflora communities, short-chain fatty acids (SCFAs), and the rate of antibiotic resistance were monitored at different time points before and after the administration of ADP. Salmonella Typhimurium inoculation was used to assess the gut microbiota’s colonization barrier over a period of three days. The results indicate long-term exposure to higher levels of ADP (16 and 128 mg/L) disrupted the colonization barrier of intestinal flora and increased the proportion of resistant bacteria. 16S rRNA sequencing data indicate that high levels of ADP caused significant changes in gut microbiota, especially Bacteroides fragilis and Bacteroides uniformis. This study assessed the microbiological safety of ADP in vitro for the first time by simulating the human gut microbiota environment. The findings showed that 1 mg/L was the no observable adverse effect concentration, and the microbiological acceptable daily intake was determined to be 91.67 µg/kg.BW/day.

Aditoprim （ADP）是一种新型的二氢叶酸还原酶抑制剂。抗菌活性强，毒性低，无致突变性。这些特征使其成为临床兽医及其对人类影响的进一步研究的有希望的候选者。因此，本研究旨在探讨ADP对人体微生物群的影响。将ADP（0,1,16和128mg/L）添加到含有人肠道菌群的趋化剂中。在给药前后不同时间点监测微生物群落、短链脂肪酸（SCFAs）和抗生素耐药率。鼠伤寒沙门菌接种被用来评估肠道菌群在三天内的定植屏障。结果表明，长期暴露于较高水平的ADP（16和128mg/L）会破坏肠道菌群的定植屏障，增加耐药菌的比例。16S rRNA测序数据表明，高水平ADP导致肠道微生物群发生显著变化，尤其是脆弱拟杆菌和均匀拟杆菌。本研究通过模拟人体肠道菌群环境，首次对ADP体外微生物安全性进行评估。结果表明，1mg/L为无明显不良反应浓度，微生物可接受日摄入量为91.67µg/kg.BW/day。

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引用次数: 0

Comparison of the serum levels of proteins involved in microtubule stabilization in patients with alcohol or heroin use disorder 酒精或海洛因使用障碍患者参与微管稳定的血清蛋白水平的比较

IF 2.9 3区医学 Q2 TOXICOLOGY

Toxicology letters

Pub Date : 2025-12-01 DOI: 10.1016/j.toxlet.2025.111782

Huseyin Kayadibi , İhsan Cetin , Mehmet Emrah Karadere , Ece Yazla

Aim

In patients with alcohol or heroin use disorder, we aimed to examine the effects of alcohol or heroin use and treatment on the serum levels of microtubule stabilization proteins.

Method

A total of 64 patients with 32 alcohol and 32 heroin use disorder, and age-gender matched healthy volunteers were included in this study. Fasting blood samples were taken from patients before and after three weeks of treatment, and from healthy volunteers on the first working day after first interview.

Results

Compared to healthy controls, there were statistically significant decreases for serum levels of microtubule associated protein-2, tau protein, phospho tau protein, glial fibrillary acidic protein, glial cell line derived neurotrophic factor and progranulin, while there was a statistically significant increase for serum levels of Nogo-A in patients with alcohol use disorder (P < 0.001, P < 0.001, P < 0.001, P < 0.001, P < 0.001, P = 0.002 and P < 0.001, respectively). In patients with heroin use disorder compared to healthy controls, there was a statistically significant increase only for serum level of Nogo-A (P < 0.001). Only post-treatment serum progranulin level of patients with alcohol use disorder was statistically significantly higher than pre-treatment levels (P = 0.040).

Conclusion

It was considered that these proteins may be a potential biomarker in terms of reflecting molecular level of damage caused by alcohol or heroin use, as well as distinguishing patients with and without alcohol or heroin use disorder. Further studies with long term treatments may be performed to investigate the optimum therapy period, since three weeks of treatment may not be enough to repair this damage.

针对酒精或海洛因使用障碍患者，我们旨在研究酒精或海洛因使用和治疗对血清微管稳定蛋白水平的影响。方法选取64例酒精和海洛因使用障碍患者（32例）和年龄性别匹配的健康志愿者进行研究。患者在治疗前和治疗后三周的空腹血样，以及健康志愿者在第一次访谈后的第一个工作日的空腹血样。ResultsCompared健康对照组,有显著降低血清protein-2相关的微管,tau蛋白质、磷τ蛋白胶质原纤维酸性蛋白、胶质细胞系衍生神经营养因子和progranulin,有统计上显著的增加患者的血清水平的Nogo-A酒精使用障碍(P & lt; 0.001,P & lt; 0.001,P & lt; 0.001,P & lt; 0.001,P & lt; 0.001,P = 0.002 P & lt; 0.001,分别)。与健康对照组相比，海洛因使用障碍患者的血清Nogo-A水平有统计学意义的升高（P <； 0.001）。只有治疗后酒精使用障碍患者血清前颗粒蛋白水平高于治疗前水平，差异有统计学意义（P = 0.040）。结论这些蛋白可能是一个潜在的生物标志物，可以反映酒精或海洛因使用引起的分子水平损伤，以及区分有无酒精或海洛因使用障碍患者。由于三周的治疗可能不足以修复这种损伤，因此可以进行长期治疗的进一步研究，以调查最佳治疗期。

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引用次数: 0

Reproductive effects of dibutyl phthalate (DBP) toxicity in the testes of mammalian and avian species 邻苯二甲酸二丁酯（DBP）毒性对哺乳动物和鸟类睾丸的生殖影响。

IF 2.9 3区医学 Q2 TOXICOLOGY

Toxicology letters

Pub Date : 2025-11-19 DOI: 10.1016/j.toxlet.2025.111779

Musa Zakariah , Reneilwe.A. Molele , Mohammed A.A. Mahdy , Ibrahim S. Harande , Esther Z. Musa , Josephine J. Dasa , Lyndy.J. McGaw

Dibutyl phthalate (DBP), a widely used phthalic acid esters (PAEs), is a well-studied endocrine-disrupting chemical. It is one of the most and studied endocrine disruptors associated with reproductive disorders and infertility. Despite its prevalence, its exact mechanisms of action remain poorly understood. This review provides an overview of DBP’s reproductive toxicity and explores its mechanisms in mammalian and avian species. Exposure to DBP during sexual differentiation disrupts the proliferation and maturation of Sertoli and Leydig cells, potentially leading to cryptorchidism, hypospadias, a shortened anogenital distance, and abnormal penile development in mammalian species. Additionally, it can cause atrophy of the seminiferous tubules and apoptosis of spermatogenic cells in both mammalian and avian species. Its effects are multifaceted, operating at hormonal levels by altering the release of hypothalamic, pituitary, and peripheral hormones, and at intracellular level by disrupting signalling cascades, nuclear and membrane receptors, altered steroidogenic gene expression, DNA disruption, and alteration of vimentin cytoskeleton proteins. It is important to note that the severity of reproductive toxicity varies between species at identical DBP concentrations, likely due to differences in metabolism. Nonetheless, existing data consistently implicate DBP in reproductive malformations that can lead to male infertility across species. This review highlights the need for further research into low-dose effects and species-specific responses to better understand and mitigate DBP’s impact on reproductive health.

邻苯二甲酸二丁酯（DBP）是一种广泛使用的邻苯二甲酸酯（PAEs），是一种经过充分研究的内分泌干扰化学物质。它是研究最多的与生殖障碍和不孕症有关的内分泌干扰物之一。尽管它很普遍，但其确切的作用机制仍然知之甚少。本文综述了DBP的生殖毒性，并探讨了其在哺乳动物和鸟类中的作用机制。在哺乳动物的性分化过程中，暴露于DBP会破坏支持细胞和间质细胞的增殖和成熟，可能导致隐睾症、尿道下裂、肛门生殖器距离缩短和阴茎发育异常。此外，它可以导致哺乳动物和鸟类的精小管萎缩和生精细胞凋亡。它的作用是多方面的，在激素水平上通过改变下丘脑、垂体和外周激素的释放而起作用，在细胞内水平上通过破坏信号级联、核和膜受体、改变类固醇基因表达、DNA破坏和静脉蛋白细胞骨架蛋白的改变而起作用。值得注意的是，在相同DBP浓度下，不同物种的生殖毒性的严重程度不同，可能是由于代谢的差异。尽管如此，现有数据一致表明DBP在生殖畸形中可能导致跨物种雄性不育。本综述强调需要进一步研究DBP的低剂量效应和物种特异性反应，以更好地了解和减轻DBP对生殖健康的影响。

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引用次数: 0

Co-exposure to low levels of DEHP, procymidone, Cd2 + , Pb2+, and 1-nitropyrene may damage mouse ovary and uterus via Hippo pathway and circPVT1 共同暴露于低水平DEHP、原胺酮、Cd2+、Pb2+和1-硝基芘可通过Hippo通路和circPVT1损伤小鼠卵巢和子宫。

IF 2.9 3区医学 Q2 TOXICOLOGY

Toxicology letters

Pub Date : 2025-11-19 DOI: 10.1016/j.toxlet.2025.111770

Yushan Li , Hui Nie , Shiyun He , Jiaxin Zhang , Hu Fu , Yongfei Zhu

High doses of Di-(2-ethylhexyl) phthalate (DEHP), procymidone (PCM), Cd²⁺, Pb²⁺, and 1-nitropyrene (1-NP) induce reproductive toxicity in female experimental animals. However, evidence regarding female reproductive toxicity at low levels of combined exposure (co-exposure) to these substances is lacking. In this study, these environmental chemicals, which met or minimally exceeded the relevant standards, were administered simultaneously to 4-week-old female mice. After 21 days of exposure, the mice were kept feeding for 1 week and then sacrificed. Subsequently, their blood, ovaries, and uteri were taken. Co-exposure to concentrations ≥ 1/3 of the maximum allowable concentration (MAC) for each of these chemicals, as per relevant standards, was revealed to impair ovarian and uterine development in mice. This exposure activated the Hippo pathway, resulting in a decrease in ERα and circPVT1, and an elevation of miR-149. Co-exposure to these compounds in levels marginally lower than the MACs of each chemical also elevated cleaved CASPASE-3 levels. These changes showed a dose–response relationship. Joint exposure to these substances at values ≥ 1/3 of each average concentration in the blood could elicit similar biological effects in the ovaries and uteri cultured in vitro. Therefore, this study hypothesized that co-exposure to low levels of these environmental chemicals results in ovarian and uterine impairment in mice and that this damage may be linked to the activation of the Hippo pathway, downregulation of ERα and circPVT1, and upregulation of miR-149.

高剂量邻苯二甲酸二（2-乙基己基）酯（DEHP）、原胺酮（PCM）、Cd2+、Pb2+和1-硝基芘（1-NP）对雌性实验动物具有生殖毒性。然而，缺乏关于低水平联合暴露（共同暴露）于这些物质的女性生殖毒性的证据。在本研究中，这些环境化学物质达到或最低超过相关标准，同时给予4周龄的雌性小鼠。暴露21 d后，饲养1周后处死。随后，采集了他们的血液、卵巢和子宫。根据相关标准，这些化学物质中每一种的最大允许浓度(MAC)≥1/3的浓度共同暴露会损害小鼠卵巢和子宫的发育。这种暴露激活了Hippo通路，导致ERα和circPVT1降低，miR-149升高。以略低于每种化学物质的MACs水平共同暴露于这些化合物中也会提高裂解CASPASE-3水平。这些变化呈剂量-反应关系。在体外培养的卵巢和子宫中，当这些物质在血液中浓度≥各平均浓度的1/3时，联合暴露在这些物质中也会产生类似的生物学效应。因此，本研究假设，共同暴露于低水平的这些环境化学物质会导致小鼠卵巢和子宫损伤，这种损伤可能与Hippo通路的激活、ERα和circPVT1的下调以及miR-149的上调有关。

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引用次数: 0

Long-term supplementation of taurine induces hepatic steatosis and disrupts bile acid homeostasis in male mice 长期补充牛磺酸可诱导雄性小鼠肝脂肪变性并破坏胆汁酸稳态。

IF 2.9 3区医学 Q2 TOXICOLOGY

Toxicology letters

Pub Date : 2025-11-19 DOI: 10.1016/j.toxlet.2025.111778

Tong Shi , Shu-Yun Zhang

Taurine, a sulfur-containing amino acid, is widely used in energy drinks and nutraceuticals. However, the long-term effects of taurine supplementation on liver metabolism remain incompletely understood. Here, male C57BL/6 mice were administered 3 % taurine in drinking water for 32 weeks. Taurine treatment reduced body weight and abdominal fat, suggesting potential anti-obesity effects. However, hepatic lipid accumulation and steatosis were evident in taurine-treated mice. Serum levels of alanine aminotransferase, alkaline phosphatase, cholesterol, non-esterified fatty acids (NEFA), total bile acids, and hepatic triglycerides were markedly elevated. Taurine significantly upregulated hepatic expression of the fatty acid transporter Cd36, thereby enhancing hepatic fatty acid uptake and promoting lipid deposition, while increasing lipolytic enzymes Atgl and Hsl expression in white adipose tissue, contributing to increased circulating NEFA and subsequent hepatic lipid accumulation. Moreover, taurine disrupted the negative feedback regulation of bile acid biosynthesis in the enterohepatic circulation, increased bile acid synthesis and uptake, altered bile acid transport, and elevated both conjugated and unconjugated bile acid species. Histological and molecular analyses further revealed taurine-induced hepatic inflammation, characterized by perivascular immune cell infiltration and upregulation of pro-inflammatory cytokines and mediators. Importantly, taurine-induced metabolic alterations in lipid and bile acid homeostasis were evident as early as 5 weeks, preceding the onset of histological steatosis. Collectively, these findings demonstrate that prolonged taurine supplementation promotes hepatic steatosis and inflammation, accompanied by dysregulation of bile acid homeostasis. The study highlights the potential metabolic risks associated with chronic taurine intake and underscores the need for caution when considering taurine-based health supplements.

牛磺酸是一种含硫氨基酸，广泛用于能量饮料和营养食品中。然而，补充牛磺酸对肝脏代谢的长期影响仍不完全清楚。在这里，雄性C57BL/6小鼠在饮用水中添加3%牛磺酸，持续32周。牛磺酸治疗降低了体重和腹部脂肪，表明潜在的抗肥胖作用。然而，在牛磺酸处理的小鼠中，肝脏脂质积累和脂肪变性明显。血清丙氨酸转氨酶、碱性磷酸酶、胆固醇、非酯化脂肪酸（NEFA）、总胆汁酸和肝甘油三酯水平显著升高。牛磺酸显著上调肝脏脂肪酸转运体Cd36的表达，从而增强肝脏脂肪酸摄取，促进脂质沉积，同时增加白色脂肪组织中脂溶酶Atgl和Hsl的表达，导致循环NEFA增加，进而导致肝脏脂质积累。此外，牛磺酸破坏了肠肝循环中胆汁酸生物合成的负反馈调节，增加了胆汁酸的合成和摄取，改变了胆汁酸的运输，增加了共轭和非共轭胆汁酸的种类。组织学和分子分析进一步揭示了牛磺酸诱导的肝脏炎症，其特征是血管周围免疫细胞浸润和促炎细胞因子和介质的上调。重要的是，牛磺酸诱导的脂质和胆汁酸稳态代谢改变早在组织学脂肪变性发生前5周就很明显。总的来说，这些发现表明，长期补充牛磺酸会促进肝脏脂肪变性和炎症，并伴有胆汁酸稳态失调。该研究强调了长期摄入牛磺酸的潜在代谢风险，并强调在考虑牛磺酸类保健品时需要谨慎。

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引用次数: 0

Transgenerational toxicity of tralomethrin in zebrafish: Parental exposure induces developmental defects in offspring 氯氰菊酯对斑马鱼的跨代毒性：亲代接触诱发后代发育缺陷。

IF 2.9 3区医学 Q2 TOXICOLOGY

Toxicology letters

Pub Date : 2025-11-18 DOI: 10.1016/j.toxlet.2025.111777

Yueping Huang , Wenmin Feng , Jinli Zhang , Yafang Shi , Peng Xiao , Wenhua Li

Tralomethrin (TRA), a widely used type II pyrethroid insecticide, belongs to a class of pesticides frequently detected in aquatic environments, raising concerns about its potential chronic and transgenerational toxicity. This study aimed to evaluate the long-term effects of environmentally relevant concentrations of TRA (0.05, 0.5, and 5 μg/L) on adult zebrafish and their offspring. Adult zebrafish were exposed to TRA for 150 days, during which phenotypic observations, histological assessments, biochemical assays, transcriptomic profiling, and developmental evaluations of F1 progeny were conducted. Following TRA exposure, male zebrafish exhibited increased body weight, and a significant decline in spawning rate was observed. Histological and biochemical analyses revealed gill and ovarian abnormalities, accompanied by oxidative stress and apoptosis in ovarian tissues. Transcriptomic analysis of TRA-exposed ovaries revealed gene enrichment in glutathione metabolism and signaling pathways including Hedgehog and Wnt, reflecting oxidative stress and developmental disruption. In the F1 generation, TRA exposure led to decreased survival and hatching rates, along with developmental abnormalities including pericardial edema, spinal curvature, and impaired swim bladder inflation. Gene expression analyses of swim bladder marker genes and regulatory pathways further corroborated TRA-induced disruption in organogenesis. Overall, these findings demonstrate that chronic TRA exposure can induce multi-level toxic effects in zebrafish, including reproductive impairment and transgenerational developmental defects. This study highlights the urgent need to assess the ecological risks of pyrethroid pesticides and to incorporate long-term and transgenerational endpoints into environmental risk assessment.

氯氰菊酯（Tralomethrin， TRA）是一种广泛使用的II型拟除虫菊酯杀虫剂，属于在水生环境中经常检测到的一类农药，其潜在的慢性和跨代毒性引起了人们的关注。本研究旨在评估环境相关浓度的TRA（0.05、0.5和5μg/L）对成年斑马鱼及其后代的长期影响。将成年斑马鱼暴露于TRA 150天，在此期间进行表型观察、组织学评估、生化分析、转录组分析和F1后代发育评估。暴露于TRA后，雄性斑马鱼体重增加，产卵率显著下降。组织学和生化分析显示鳃和卵巢异常，伴有卵巢组织氧化应激和细胞凋亡。转录组学分析显示，暴露于tra的卵巢中谷胱甘肽代谢和包括Hedgehog和Wnt在内的信号通路的基因富集，反映了氧化应激和发育中断。在F1代中，TRA暴露导致成活率和孵化率下降，并伴有发育异常，包括心包水肿、脊柱弯曲和鳔膨胀受损。对鱼鳔标记基因和调控途径的基因表达分析进一步证实了tra在器官发生中诱导的破坏。总的来说，这些发现表明，长期暴露于TRA可以诱导斑马鱼的多层次毒性作用，包括生殖损伤和跨代发育缺陷。这项研究强调了评估拟除虫菊酯类杀虫剂的生态风险的迫切需要，并将长期和跨代终点纳入环境风险评估。

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引用次数: 0

Hematological effects of chronic heavy metal exposure in children from marginalized occupational communities in Mexico 墨西哥边缘化职业社区儿童慢性重金属暴露的血液学影响

IF 2.9 3区医学 Q2 TOXICOLOGY

Toxicology letters

Pub Date : 2025-11-14 DOI: 10.1016/j.toxlet.2025.111776

Karen B. Méndez-Rodríguez , Francisco J. Pérez-Vázquez , Evelyn Van Brussel , Ana K. González-Palomo , Axel Reyes-Zavala , Kelvin Saldaña-Villanueva

Children engaged in precarious labor activities may experience exposure to environmental contaminants, including heavy metals, particularly in marginalized communities. Limited evidence exists regarding the potential hematological implications of such exposures in pediatric populations. A cross-sectional study was conducted among 50 children (<18 years) from three communities in San Luis Potosí, Mexico, engaged in informal recycling (Zone B), artisanal brickmaking (Zone C), or artisanal stone-carving (Zone A). Urinary concentrations of 15 metals were determined by ICP–MS, and hematological parameters were assessed using an automated analyzer. Associations were examined using nonparametric statistics, age-adjusted correlations, Bayesian Kendall’s Tau analysis, and post hoc power evaluation. Distinct urinary metal profiles and hematological parameters were observed across the study zones. Zone B showed higher concentrations of Cr, Co, Ni, Al, and Sn, whereas As was elevated in Zone C. Hematological differences included higher WBC, lymphocyte, granulocyte counts, and MPV in Zone C. Age-adjusted correlations identified associations of As with WBC, lymphocyte, and granulocyte counts; Co with platelet indices; and negative correlations of Ni, Al, and Sn with several hematological variables. Bayesian analysis confirmed robust associations for Co with WBC, Al with granulocytes, and Sn with MPV. This study provides exploratory evidence of associations between urinary metal concentrations and hematological parameters in children engaged in precarious labor activities. While preliminary, the findings underscore the importance of child-focused public health strategies and support the need for larger, longitudinal studies to validate these associations and clarify their implications.

从事危险劳动活动的儿童可能会接触到环境污染物，包括重金属，特别是在边缘化社区。关于儿童人群中此类暴露的潜在血液学影响的证据有限。一项横断面研究在50名儿童(

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引用次数: 0

Chronicle of mixture effects: Sensitivity differences in multiple toxicity endpoints of transgenic C. elegans and assessment of combined toxicity interactions 混合效应的编年史：转基因秀丽隐杆线虫在多个毒性终点的敏感性差异和联合毒性相互作用的评估。

IF 2.9 3区医学 Q2 TOXICOLOGY

Toxicology letters

Pub Date : 2025-11-14 DOI: 10.1016/j.toxlet.2025.111774

Peng Huang , Shu-Shen Liu , Jiake Li , Dongqi Wang

The pesticide, as the typical emerging contaminants, has brought significant benefits to agricultural production due to its widespread use. However, the excessive residue of pesticides in environmental media poses potential risks to both the environment and human health. Therefore, this study focused on three typical pesticide residues (aldicarb (ALD)，methamidophos (MET) and triazophos (TAP)) that were commonly detected in fruits and vegetables, using the DAF-16 transgenic strain of Caenorhabditis elegans (C. elegans) as a model organism. Three binary and one ternary mixture systems were designed using the direct equipartition ray design and the uniform design ray method, resulting in a total of 20 mixture rays. These were used for multi-endpoint toxicity tests on C. elegans. The results indicated that all mixture rays exhibited higher sensitivity at the endpoints of lifespan and reproduction inhibition compared to the mortality endpoint. Furthermore, the sensitivity to lifespan and reproduction inhibition varied across the different mixture rays. The mixture toxicity interaction assessment results indicated that with increasing toxicity effects, a concentration ratio-dependent phenomenon was observed in the toxicity interactions. Furthermore, when the effect level exceeded 30 %, opposite toxicity interaction outcomes (i.e., the shift from antagonism to synergism or vice versa) emerged across different toxicological endpoints. These findings pose significant challenges for the assessment of mixture combined toxicity.

农药作为典型的新兴污染物，由于其广泛的应用，给农业生产带来了显著的效益。然而，环境介质中农药的过量残留对环境和人类健康都有潜在的风险。因此，本研究以DAF-16转基因秀丽隐杆线虫（Caenorhabditis elegans， C. elegans）为模式生物，针对水果和蔬菜中常见的三种典型农药残留（涕灭威（ALD）、甲胺磷（MET）和三唑磷（TAP））进行了研究。采用直接均分射线设计和均匀设计射线法设计了3个二元和1个三元混合体系，共得到20个混合射线。这些被用于秀丽隐杆线虫的多终点毒性试验。结果表明，与死亡终点相比，所有混合射线在寿命和繁殖抑制终点表现出更高的敏感性。此外，不同混合射线对寿命和繁殖抑制的敏感性也不同。混合物毒性相互作用评价结果表明，随着毒性作用的增加，毒性相互作用存在浓度比依赖现象。此外，当效应水平超过30%时，不同毒理学终点出现相反的毒性相互作用结果（即从拮抗到协同或反之亦然）。这些发现对混合物联合毒性的评估提出了重大挑战。

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引用次数: 0

Neurovascular toxicity of dichlorvos: Crosstalk between endothelial dysfunction and neurodegeneration 敌敌畏的神经血管毒性：内皮功能障碍和神经变性之间的串扰。

IF 2.9 3区医学 Q2 TOXICOLOGY

Toxicology letters

Pub Date : 2025-11-13 DOI: 10.1016/j.toxlet.2025.111775

Igbayilola Yusuff Dimeji , Ngabea Murtala , Adekola Saheed Ayodeji , Hmaidu Lawan Jabba

O,O-Dimethyl O-(2,2-dichlorovinyl) phosphate (DDVP), commonly referred to as dichlorvos, is one of the most widely used organophosphorus insecticides for agricultural and domestic pest control, especially in low- and middle-income countries, due to its low cost and effectiveness. While acute neurotoxicity through the irreversible inhibition of AChE and subsequent cholinergic overstimulation is well documented, there is growing evidence that DDVP exerts broader chronic effects, particularly those involving the neurovascular system. Specifically, endothelial dysfunction and disruption of the bloodbrain barrier have been shown to be early events that link vascular injury to neurodegeneration. These databases included PubMed, Scopus, Web of Science, ScienceDirect, EMBASE, and the Toxicology Data Network. The terms used in the search included "dichlorvos," "DDVP," "organophosphate pesticide," "neurotoxicity," "endothelial dysfunction," "bloodbrain barrier," "neurodegeneration," "oxidative stress," and "crosstalk." The inclusion criterion was peer-reviewed studies published in English between 2000 and 2025, which involved in vivo and in vitro experimental studies that reported DDVP-induced neurovascular toxicity. Studies not related to DDVP, publications in languages other than English, and non-peer-reviewed sources were excluded. Studies suggest that DDVP impairs endothelial integrity through disrupting the homeostasis of oxidative stress, nitric oxide, and inflammatory signalling. This type of endothelial insult impairs selectivity in BBB permeability, enabling the infiltration of circulating toxins and cytokines into the central nervous system, thus promoting neuronal apoptosis, mitochondrial dysfunction, and neuroinflammation. These findings suggest that the neurotoxicity of DDVP extends beyond synaptic cholinergic mechanisms but includes neurovascular-crosstalk-driven degeneration. This review synthesizes current mechanistic insights into DDVP-induced neurovascular toxicity and recognizes the neurovascular unit as a critical target in organophosphate poisoning. Elucidation of the interplay between endothelial dysfunction and neuronal injury opens new avenues for risk assessment, preventive strategies, and therapeutic interventions for pesticide-related neurodegenerative disorders.

O，O-二甲基O-（2,2-二氯乙烯基）磷酸盐（DDVP），通常被称为敌敌畏，是农业和家庭病虫害防治中使用最广泛的有机磷杀虫剂之一，特别是在低收入和中等收入国家，因为它的成本低，效果好。尽管对乙酰胆碱酯酶的不可逆抑制和随后的胆碱能过度刺激引起的急性神经毒性已得到充分证明，但越来越多的证据表明，DDVP具有更广泛的慢性效应，特别是涉及神经血管系统的慢性效应。具体而言，内皮功能障碍和血脑屏障的破坏已被证明是血管损伤与神经变性相关的早期事件。这些数据库包括PubMed、Scopus、Web of Science、ScienceDirect、EMBASE和毒理学数据网络。搜索中使用的术语包括“敌敌畏”、“敌敌畏”、“有机磷农药”、“神经毒性”、“内皮功能障碍”、“血脑屏障”、“神经变性”、“氧化应激”和“相声”。纳入标准是2000年至2025年间以英文发表的同行评议研究，涉及报道ddvp诱导的神经血管毒性的体内和体外实验研究。与DDVP无关的研究、非英语语言的出版物和非同行评议来源被排除在外。研究表明，DDVP通过破坏氧化应激、一氧化氮和炎症信号的稳态来损害内皮细胞的完整性。这种类型的内皮损伤损害血脑屏障通透性的选择性，使循环毒素和细胞因子渗入中枢神经系统，从而促进神经元凋亡、线粒体功能障碍和神经炎症。这些发现表明，DDVP的神经毒性超出了突触胆碱能机制，但包括神经血管串扰驱动的变性。这篇综述综合了目前ddvp诱导的神经血管毒性的机制见解，并认识到神经血管单位是有机磷中毒的关键靶点。阐明内皮功能障碍和神经元损伤之间的相互作用，为农药相关神经退行性疾病的风险评估、预防策略和治疗干预开辟了新的途径。

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引用次数: 0