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Melatonin promotes cytotoxicity while reducing cell motility and antioxidant defenses in ovarian cancer cell lines 褪黑素促进细胞毒性,同时降低卵巢癌细胞系的细胞运动性和抗氧化防御
Q1 Environmental Science Pub Date : 2025-10-28 DOI: 10.1016/j.toxrep.2025.102149
Henrique Spaulonci Silveira , Roberta Carvalho Cesário , Vinicius Augusto Simão , Fernando Guimarães , Fábio Rodrigues Ferreira Seiva , Debora Aparecida P.C. Zuccari , Glaura Scantamburlo Alves Fernandes , Milena Cremer de Souza , Russel J. Reiter , Luiz Gustavo de Almeida Chuffa
Ovarian cancer (OC), a highly recurrent and fatal tumor, poses diagnostic challenges due to generic symptoms and chemoresistance. Melatonin (Mel) is an indoleamine acting against tumor progression and exhibiting pro-oxidative actions in tumor cells. This in vitro study explores the impact of Mel on antioxidant defenses of OC cells (high-grade SKOV-3 and low-grade CAISMOV-24 lines), focusing on its receptor-dependent and -independent effects. Cell viability was evaluated through MTT assay and antioxidant system was assessed in supernatants by measuring glutathione (GS), reduced (GSH) and oxidized (GSSG) glutathione, catalase (CAT), glutathione S-transferase (GST), and superoxide dismutase (SOD). Mel accumulated intracellularly and exerted cytotoxic effects, reducing cell viability in both cell lines. Notably, Mel independently of its membrane receptors, inhibited migration and invasion, thus showing its anti-tumoral potential. By investigating melatonin’s actions, we observed an impact on the antioxidant system primarily through the reduced activity of CAT and the GS axis. The modulation of these antioxidants by Mel demonstrates its multifaceted role in OC, emphasizing its therapeutic potential. We also demonstrated, for the first time, the theoretical ability of Mel to bind to CAT, which may be responsible for the reduction in enzyme activity. This study provides novel insights into Mel's receptor-independent actions and supports its potential as an adjuvant therapeutic agent in OC.
卵巢癌(OC)是一种高度复发和致命的肿瘤,由于其一般症状和化疗耐药性,给诊断带来了挑战。褪黑素(Mel)是一种吲哚胺,在肿瘤细胞中具有抗肿瘤进展和促氧化作用。本体外研究探讨了Mel对OC细胞(高级别SKOV-3和低级别CAISMOV-24系)抗氧化防御的影响,重点关注其受体依赖性和非依赖性作用。通过MTT法评估细胞活力,并通过测定谷胱甘肽(GS)、还原性(GSH)和氧化性(GSSG)谷胱甘肽、过氧化氢酶(CAT)、谷胱甘肽s -转移酶(GST)和超氧化物歧化酶(SOD)来评估上清液的抗氧化系统。Mel在细胞内积累并发挥细胞毒性作用,降低了两种细胞系的细胞活力。值得注意的是,Mel独立于其膜受体,抑制迁移和侵袭,从而显示其抗肿瘤潜力。通过研究褪黑素的作用,我们观察到褪黑素对抗氧化系统的影响主要是通过降低CAT和GS轴的活性。Mel对这些抗氧化剂的调节显示了其在OC中的多方面作用,强调了其治疗潜力。我们还首次证明了Mel与CAT结合的理论能力,这可能是导致酶活性降低的原因。这项研究为Mel的受体独立作用提供了新的见解,并支持其作为OC辅助治疗剂的潜力。
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引用次数: 0
PNA5, a glycosylated angiotensin-(1−7) mas receptor agonist for vascular dementia: A two species toxicology and toxicokinetic study PNA5,一种糖基化血管紧张素-(1−7)mas受体激动剂,用于血管性痴呆:两种毒理学和毒性动力学研究
Q1 Environmental Science Pub Date : 2025-10-28 DOI: 10.1016/j.toxrep.2025.102151
Christina Hoyer-Kimura , John P. Konhilas , Meredith Hay
PNA5 is a novel pleotropic anti-inflammatory glycosylated-Angiotensin-(1−7) peptide derivative with outstanding brain penetration and enhanced bioavailability. PNA5, via the Mas receptor, decreases brain and cerebrovascular inflammation, reduces reactive oxygen species and inflammatory cytokines production, improves cerebral blood flow, and restores cognitive function in our mouse model of VCID (Vascular contributions to cognitive impairment and dementia). This study evaluated the potential systemic and local toxicity and toxicokinetic (TK) of PNA5 following daily subcutaneous administration in Sprague Dawley rats and Beagle dogs for 28 consecutive days. PNA5 was given at 1, 5, 40 mg/kg/day to rats (n = 12) and at 1, 5, and 20 mg/kg/day in dogs (n = 6) once daily for 28 consecutive days. Blood samples were collected on days 1 and 28 for TK analysis. PNA5 was well tolerated at all doses in both species, with no test article-related mortality or adverse effects. Systemic exposure to PNA5 appeared to be independent of sex. In rats, Cmax and AUC0–2hr values increased with increasing doses. Systemic exposure to PNA5 in rats was greater on day 28 compared to day 1 following repeated administration of PNA5. In dogs, Cmax values increased less than dose-proportionally, and AUC0–2hr increased approximately dose-proportionally on days 1 and 28. Systemic exposure to PNA5 in dogs was similar on days 1 and 28 following repeated administration. These results show that PNA5 has no toxicological effects at the highest doses tested in rats or dogs and is well tolerated with repeated exposure for 28 days. Accumulation was observed in rats but not in dogs.
PNA5是一种新型的多效抗炎糖基化血管紧张素-(1−7)肽衍生物,具有出色的脑穿透性和增强的生物利用度。PNA5通过Mas受体减少脑和脑血管炎症,减少活性氧和炎症细胞因子的产生,改善脑血流量,恢复VCID小鼠模型的认知功能。本研究评估了PNA5在Sprague Dawley大鼠和Beagle犬连续28天每日皮下给药后的潜在全身和局部毒性和毒性动力学(TK)。PNA5按1、5、40 mg/kg/天剂量给鼠(n = 12),按1、5、20 mg/kg/天剂量给狗(n = 6),每天1次,连续28天。于第1天和第28天采集血样进行TK分析。PNA5在两种动物的所有剂量下都具有良好的耐受性,没有与试验品相关的死亡率或不良反应。PNA5的系统性暴露似乎与性别无关。在大鼠中,Cmax和AUC0-2hr值随剂量增加而增加。与重复给药后第1天相比,第28天大鼠全身暴露于PNA5的程度更高。在狗中,Cmax值的增加小于剂量比例,而AUC0-2hr在第1天和第28天近似剂量比例地增加。在重复给药后的第1天和第28天,犬全身暴露于PNA5的情况相似。这些结果表明,PNA5在对大鼠或狗进行的最高剂量试验中没有毒理学效应,并且在重复暴露28天后耐受性良好。在大鼠中观察到积累,但在狗中没有。
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引用次数: 0
Modulatory potential of A novel benzofuran-derived compound against aluminium chloride-induced neurotoxicity and miRNA dysregulation: Biochemical and bio-analytical study 一种新型苯并呋喃衍生化合物对氯化铝诱导的神经毒性和miRNA失调的调节潜力:生化和生物分析研究
Q1 Environmental Science Pub Date : 2025-10-25 DOI: 10.1016/j.toxrep.2025.102148
Maha Zaki Rizk , Ghadha Ibrahim Fouad , Eman Younis , Khalda Amr , Nesma Elaraby , Maha Fawzi Emam , Aya Rashad Abdou , Nesrin Fouad Taha , Laila Hasanin Emara , Hanan Farouk Aly
The aim of the current work was to investigate the neuro-modulatory activities of a novel synthesized compound, namely, 3-((3-Acetylphenyl) amino)-1-(benzofuran-2-yl) prop-2-en-1-one (designated as compound IV) in aluminium-chloride (AlCl3)-intoxicated rats. Moreover, for the first time, quantitative analysis of compound-IV in rat plasma was developed using a novel, properly validated Ultra-High-Performance-Liquid Chromatography / Ultra-Violet (UHPLC/UV) method. For the biochemical studies; four-groups were included: negative-control, AlCl3-intoxicated-rats, intoxicated-rats treated with compound-IV, and reference-donepezil, respectively. Biochemical/molecular assays were conducted; levels of interleukin-6 (IL-6), total antioxidant-capacity (TAC), brain-derived-neurotrophic-factor (BDNF), and total protein content (TP). Differential expressions of miRNA-34a, miRNA-15a, and miRNA-132, were assessed. For the bio-analytical studies; several chromatographic-conditions and extraction-procedures were meticulously optimized. Biochemical results revealed that AlCl3 (a neurotoxic-agent), enhanced neuroinflammation, oxidative-stress and synaptic-dysfunction; as indicated by increased IL-6 levels, declined both TAC levels and BDNF contents. Moreover, significant dysregulation in miR-34a, −15a, and −132 levels were observed. In contrast, treatment of neuro-intoxicated rats with compound-IV ameliorated all the investigated biomarkers. This novel-benzofuran-derivative exerts its neurotherapeutic-activity by reducing AlCl3-induced neurotoxicity and mitigating oxidative-stress, neuroinflammation, and synaptic-dysfunction through regulating all miRNA levels. The developed and validated analytical-method ensured that best quantitative separation of compound-IV was achieved using Symmetry-C18-column, with mobile phase consisting of acetonitrile: H2O (50: 50), UV detection at λmax 390-nm, 1 mL/min flow-rate and 3.4 min retention time. The proposed method provides excellent specificity and linearity over concentration range of 1–100 μg/mL; hence, it could serve as a perquisite-step for further investigation of bioavailability (BA) and pharmacokinetics (PKs) of this compound.
本研究的目的是研究一种新合成的化合物3-((3-乙酰苯基)氨基)-1-(苯并呋喃-2-基)丙-2-烯-1-酮(称为化合物IV)对氯化铝(AlCl3)中毒大鼠的神经调节活性。此外,首次建立了一种新型的、经过适当验证的超高高效液相色谱/紫外(UHPLC/UV)方法对大鼠血浆中化合物iv进行定量分析。用于生化研究;四组分别为阴性对照组、alcl3中毒大鼠、化合物iv中毒大鼠和参比多奈哌齐。进行生化/分子分析;白细胞介素-6 (IL-6)、总抗氧化能力(TAC)、脑源性神经营养因子(BDNF)和总蛋白含量(TP)的水平。评估miRNA-34a、miRNA-15a和miRNA-132的差异表达。用于生物分析研究;对色谱条件和提取工艺进行了优化。生化结果显示,AlCl3(一种神经毒性物质)可增强神经炎症、氧化应激和突触功能障碍;IL-6水平升高,TAC水平和BDNF含量均下降。此外,观察到miR-34a, - 15a和- 132水平明显失调。相比之下,用化合物- iv治疗神经中毒大鼠改善了所有研究的生物标志物。这种新型苯并呋喃衍生物通过调节所有miRNA水平,降低alcl3诱导的神经毒性,减轻氧化应激、神经炎症和突触功能障碍,发挥其神经治疗活性。采用symmetry - c18色谱柱,流动相为乙腈:H2O(50:50),紫外检测波长为λmax 390 nm,流速为1 mL/min,保留时间为3.4 min,建立并验证了该方法对化合物- iv的最佳定量分离效果。该方法在1 ~ 100 μg/mL的浓度范围内具有良好的特异性和线性;因此,它可以作为进一步研究该化合物的生物利用度(BA)和药代动力学(PKs)的先决条件。
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引用次数: 0
Comparative analysis of antioxidant and antimicrobial potentials of different extracts of Turraea vogelii leaves 土鳖叶不同提取物抗氧化和抑菌活性的比较分析
Q1 Environmental Science Pub Date : 2025-10-23 DOI: 10.1016/j.toxrep.2025.102146
Olorunfemi R. Molehin , Oluwasegun S. Dauda , Oluwakemi V. Adeleke , Joy F. David , Testimony O. Oso , Anne A. Adeyanju
Turraea vogelii Hook.f. is a plant valued for its medicinal properties. The aim of this study is to investigate the comparative analysis of antioxidant and antimicrobial potentials of different extracts of Turrea vogelii Hook.f. leaves. The fresh leaves of the plant were harvested, air-dried, ground, and extracted with three solvents based on polarity (Dichloromethane (DCM), Ethyl Acetate, and n-hexane) via a maceration procedure. The antioxidant and antibacterial potential of these compounds was tested to assess their efficacy. Fourier Transform Infrared Spectroscopy (FTIR) and Gas Chromatography Mass Spectrometry (GC-MS) were used to analyse the functional groups and organic compounds present in the drug materials, respectively. Antioxidant screening identified flavonoids (24.63 ± 0.47, 19.96 ± 0.17, 21.04 ± 0.04), phenols (20.18 ± 0.4, 17.61 ± 0.11, 8.65 ± 0.15) in 100μg/mL of the DCM, ethyl acetate, and n-hexane crude extracts, respectively. The antibacterial evaluation showed that the DCM extract demonstrated potent activity, with minimum inhibitory concentration (MIC) values as low as 3.125 µg/mL and minimum bactericidal concentration (MBC) values ranging from 6.25 µg/mL to 50 µg/mL against pathogens such as Escherichia coli ATCC 35218, Staphylococcus aureus ATCC 2921, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 700303, and Salmonella typhi ATCC14028. FTIR analysis identified several functional groups in the extract, including hydroxyls, alkanes, amides, ethers, and amines, indicative of diverse bioactive compounds, and GC-MS identified key compounds like squalene and Hexanoic acid. The results highlight the potential of plant leaves to possess notable antioxidants and antibacterial properties, supporting their traditional use in folk medicine and paving the way for the development of novel antibacterial agents.
Turraea vogelii Hook.f。是一种有药用价值的植物。摘要本研究旨在对杜鹃不同提取物的抗氧化和抗菌活性进行比较分析。叶子。植物的新鲜叶子被收获,风干,研磨,并通过浸渍程序用三种溶剂(二氯甲烷(DCM),乙酸乙酯和正己烷)提取。对这些化合物的抗氧化和抗菌潜力进行了测试,以评估其功效。采用傅里叶变换红外光谱(FTIR)和气相色谱质谱(GC-MS)分别对药材中的官能团和有机化合物进行了分析。抗氧化剂筛选确定类黄酮(24.63 ± 0.47,19.96 ± 0.17,21.04 ±0.04 )、酚类(20.18 ± 0.4,17.61 ± 0.11,8.65 ±0.15 )100年DCM的μg / mL,乙酸乙酯,分别和原油正己烷提取物。抑菌评价表明,DCM提取物对大肠杆菌ATCC 35218、金黄色葡萄球菌ATCC 2921、大肠杆菌ATCC 25922、铜绿假单胞菌ATCC 27853、肺炎克雷伯菌ATCC 700303、伤寒沙门氏菌ATCC14028等病原菌具有较强的抑菌活性,最低抑菌浓度(MIC)为3.125 µg/mL,最低杀菌浓度(MBC)为6.25 µg/mL ~ 50 µg/mL。FTIR分析鉴定了提取物中的几个官能团,包括羟基、烷烃、酰胺、醚和胺,表明了多种生物活性化合物,GC-MS鉴定了关键化合物,如角鲨烯和己酸。研究结果表明,植物叶片具有显著的抗氧化和抗菌特性,支持其在民间医学中的传统应用,并为开发新型抗菌剂铺平了道路。
{"title":"Comparative analysis of antioxidant and antimicrobial potentials of different extracts of Turraea vogelii leaves","authors":"Olorunfemi R. Molehin ,&nbsp;Oluwasegun S. Dauda ,&nbsp;Oluwakemi V. Adeleke ,&nbsp;Joy F. David ,&nbsp;Testimony O. Oso ,&nbsp;Anne A. Adeyanju","doi":"10.1016/j.toxrep.2025.102146","DOIUrl":"10.1016/j.toxrep.2025.102146","url":null,"abstract":"<div><div><em>Turraea vogelii Hook</em>.f. is a plant valued for its medicinal properties. The aim of this study is to investigate the comparative analysis of antioxidant and antimicrobial potentials of different extracts of <em>Turrea vogelii Hook</em>.f. leaves. The fresh leaves of the plant were harvested, air-dried, ground, and extracted with three solvents based on polarity (Dichloromethane (DCM), Ethyl Acetate, and n-hexane) via a maceration procedure. The antioxidant and antibacterial potential of these compounds was tested to assess their efficacy. Fourier Transform Infrared Spectroscopy (FTIR) and Gas Chromatography Mass Spectrometry (GC-MS) were used to analyse the functional groups and organic compounds present in the drug materials, respectively. Antioxidant screening identified flavonoids (24.63 ± 0.47, 19.96 ± 0.17, 21.04 ± 0.04), phenols (20.18 ± 0.4, 17.61 ± 0.11, 8.65 ± 0.15) in 100μg/mL of the DCM, ethyl acetate, and n-hexane crude extracts, respectively. The antibacterial evaluation showed that the DCM extract demonstrated potent activity, with minimum inhibitory concentration (MIC) values as low as 3.125 µg/mL and minimum bactericidal concentration (MBC) values ranging from 6.25 µg/mL to 50 µg/mL against pathogens such as <em>Escherichia coli</em> ATCC 35218, Staphylococcus aureus ATCC 2921, <em>Escherichia coli</em> ATCC 25922, <em>Pseudomonas aeruginosa</em> ATCC 27853, <em>Klebsiella pneumoniae</em> ATCC 700303, and <em>Salmonella typhi</em> ATCC14028. FTIR analysis identified several functional groups in the extract, including hydroxyls, alkanes, amides, ethers, and amines, indicative of diverse bioactive compounds, and GC-MS identified key compounds like squalene and Hexanoic acid. The results highlight the potential of plant leaves to possess notable antioxidants and antibacterial properties, supporting their traditional use in folk medicine and paving the way for the development of novel antibacterial agents.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102146"},"PeriodicalIF":0.0,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145361679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Activation of peroxisome proliferator-activated receptor (PPAR) by pioglitazone in oral traumatic ulcers in female rats 吡格列酮对雌性大鼠口腔创伤性溃疡中过氧化物酶体增殖物激活受体(PPAR)的激活作用
Q1 Environmental Science Pub Date : 2025-10-22 DOI: 10.1016/j.toxrep.2025.102147
Roque Soares Martins Neto , Lívia Victor da Silva, Clarice Lioba de Araújo, Angelo Gabriel Farias Valente, Antonio Alexandre Coelho, Caio Ferreira Freire Caetano, Gabriella Alves Julião Costa, Paulo Goberlânio de Barros Silva , Rafael Linard Avelar
This study aimed to evaluate the effect of pioglitazone treatment on oral ulcer healing in rats, given its potential to modulate inflammatory processes. Thirty-two animals were randomly allocated into four groups: one control and three treated with different doses of pioglitazone (5, 15, and 45 mg/kg). Oral mucosal ulceration was induced one hour after treatment using a 6 mm diameter and 1 mm deep punch. Samples were collected on days 1, 3, 7, and 14 for histological analysis with optical microscopy, while immunohistochemistry was performed to assess expression of inflammatory markers across five fields. Ulcer size significantly decreased in groups treated with 15 and 45 mg/kg compared with the control group on days 1, 3, and 7. By day 14, no differences were observed between groups, although all groups exhibited progressive reduction from day 7 onward. Histological scoring demonstrated reduced acute inflammation in pioglitazone-treated animals by day 3, evolving into mild inflammation by day 7 and minimal levels by day 14. Additionally, Pioglitazone treatment also reduced TNF-α, IL-6, and NFkB p65 levels compared to controls. This study demonstrates that pioglitazone accelerates oral healing by modulating inflammatory mediators, suggesting a novel therapeutic role in wound management.
本研究旨在评估吡格列酮治疗对大鼠口腔溃疡愈合的影响,因为它有可能调节炎症过程。32只动物随机分为4组:1组为对照组,3组给予不同剂量的吡格列酮(5、15和45 mg/kg)。用直径为6 mm,深度为1 mm的冲床治疗1小时后引起口腔黏膜溃疡。在第1天、第3天、第7天和第14天收集样本,用光学显微镜进行组织学分析,同时用免疫组织化学方法评估五个领域炎症标志物的表达。与对照组相比,15和45 mg/kg组在第1、3和7天溃疡大小显著减少。到第14天,各组之间没有观察到差异,尽管所有组都从第7天开始逐渐减少。组织学评分显示,吡格列酮治疗动物的急性炎症在第3天减轻,在第7天演变为轻度炎症,在第14天达到最低水平。此外,与对照组相比,吡格列酮治疗还降低了TNF-α、IL-6和NFkB p65水平。本研究表明吡格列酮通过调节炎症介质加速口腔愈合,提示在伤口管理中具有新的治疗作用。
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引用次数: 0
Safety evaluation of Butyricicoccus faecihominis DSM 34943 粪人丁酸球菌DSM 34943的安全性评价
Q1 Environmental Science Pub Date : 2025-10-22 DOI: 10.1016/j.toxrep.2025.102145
Jeffrey Pitt , Mark R. Bauter , Ritesh Kumar , Oliver Hasselwander , Ashley A. Hibberd , Helene Kane , Qiong Wang , Isabelle Auzanneau , Stéphanie Bry , Elisabeth David , Pauline Seguinot , Frank Burns , Amy B. Smith , Miriam Carnovale
A novel strain of Butyricicoccus faecihominis DSM 34943 was isolated from the feces of a healthy human donor. In order to fully assess the safety of this strain, a full genomic assessment, further in-vitro characterization and a combined in-vivo subchronic 28-day and 90-day toxicity study is reported herein. B. faecihominis DSM 34943 was susceptible to antibiotics of human clinical relevance, was sensitive to bile and gastric juice pH conditions, and does not exhibit any aspects of virulence. This strain also demonstrates the ability to engraft the gastrointestinal tract of rats, persisting with continuous administration of the strain until the end of the study. Exposure to 2000 mg/kg BW/day B. faecihominis DSM 34943 did not produce any evidence of toxicity after either 28- or 90-days of exposure and did not translocate across the gastrointestinal barrier. Therefore, the NOEL for B. faecihominis DSM 34943, administered for 28- or 90-days, was determined to be the limit dose at 2000 mg/kg/day in male and female rats, a level which meets or exceeds calculated dose equivalent of 1.97 × 1011 CFU/kg/day. B. faecihominis DSM 34943 activity was also evaluated in a DIO mice model and supplementation of B. faecihominis DSM 34943 resulted in significant improvement in insulin sensitivity, leptin, resistin and cholesterol levels, suggesting that this strain has potential as a safe next generation probiotic for metabolic health.
从健康人供体粪便中分离到一株新的粪人丁酸球菌DSM 34943。为了充分评估该菌株的安全性,本文报道了一项完整的基因组评估、进一步的体外鉴定以及28天和90天的体内亚慢性毒性联合研究。粪人杆菌DSM 34943对与人类临床相关的抗生素敏感,对胆汁和胃液pH值敏感,不表现出任何毒力。该菌株还显示了移植大鼠胃肠道的能力,并持续给予该菌株直到研究结束。暴露于2000 mg/kg体重/天的粪人B. DSM 34943在暴露28天或90天后没有产生任何毒性证据,也没有通过胃肠道屏障转运。因此,在给药28天或90天的情况下,雄性和雌性大鼠的极限剂量DSM 34943为2000 mg/kg/天,该剂量达到或超过计算剂量当量1.97 × 1011 CFU/kg/天。在DIO小鼠模型中也评估了B. faecihominis DSM 34943的活性,补充B. faecihominis DSM 34943可显著改善胰岛素敏感性、瘦素、抵抗素和胆固醇水平,这表明该菌株有潜力成为安全的下一代代谢健康益生菌。
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引用次数: 0
Genotoxicity evaluation of kaurenoic acid 丁香烯酸的遗传毒性评价
Q1 Environmental Science Pub Date : 2025-10-16 DOI: 10.1016/j.toxrep.2025.102144
Lonneke C. Wilms , Jennifer L.G. van de Ligt , Christine M. Crincoli , Alex K. Eapen
Genotoxicity evaluations are essential components of the safety assessment for compounds intended for ingestion. Kaurenoic acid, a naturally occurring diterpene, is found in various plant species that are under investigation for potential therapeutic and sweetening properties. Salmonella typhimurium strains TA1535, TA1537, TA98 and TA100 and Escherichia coli strain WP2uvrA were treated with kaurenoic acid using the Ames plate incorporation and pre-incubation methods. Up to eight dose levels were tested, with and without metabolic activation using 10 % rat liver S9 mix with standard co-factors. Kaurenoic acid did not induce an increase in revertant colony frequency at any dose level under either condition indicating a lack of mutagenic activity. Additionally, genotoxic potential was evaluated in human peripheral blood lymphocytes via the in vitro micronucleus assay. Duplicate cultures were treated with kaurenoic acid at four dose levels with exposure conditions including a 4-hour exposure with or without 2 % S9 and a 24-hour exposure without S9. While kaurenoic acid exhibited marked toxicity, it did not produce any statistically significant increase in micronucleated binucleate cells. The assay included a dose that induced approximately 55 ± 5 % cytostasis, consistent with current OECD guidelines. Under the conditions of these studies, kaurenoic acid demonstrated no evidence of mutagenicity, clastogenicity, or aneugenicity. When considered with existing literature, the current findings support the conclusion that kaurenoic acid does not pose a genotoxic risk.
遗传毒性评估是供摄入化合物安全性评估的重要组成部分。钙烯酸是一种天然存在的二萜,存在于多种植物中,目前正在研究其潜在的治疗和增甜特性。采用Ames平板掺入法和预孵育法对鼠伤寒沙门菌TA1535、TA1537、TA98、TA100和大肠杆菌WP2uvrA进行处理。使用10% %的大鼠肝脏S9混合标准辅助因子,测试了多达8个剂量水平,有和没有代谢激活。在两种情况下,在任何剂量水平上,钙烯酸都没有引起逆转菌落频率的增加,表明缺乏致突变活性。此外,通过体外微核试验评估了人外周血淋巴细胞的遗传毒性潜力。用四种剂量水平的钙烯酸处理重复培养物,暴露条件包括含或不含2 % S9的4小时暴露和不含S9的24小时暴露。虽然钙烯酸表现出明显的毒性,但在微核双核细胞中没有产生任何统计学意义上的显著增加。该试验包括诱导约55% ± 5 %细胞抑制的剂量,与目前的OECD指南一致。在这些研究的条件下,丁香烯酸没有表现出诱变性、致裂性或非诱变性的证据。当考虑到现有的文献,目前的研究结果支持的结论,即钙烯酸不构成遗传毒性风险。
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引用次数: 0
Microplastics and child health: A scoping review of prenatal and early-life exposure routes and potential health risks 微塑料与儿童健康:产前和生命早期接触途径和潜在健康风险的范围审查
Q1 Environmental Science Pub Date : 2025-10-14 DOI: 10.1016/j.toxrep.2025.102143
Sakuntala Nadarasan , Zhi Xin Phuna , Rahela Zaman , Chung Keat Tan , Normina Ahmad Bustami , Yu Bin Ho , Stephanie Julia Kosasih , Eugenie Sin Sing Tan
Microplastics (MPs) is defined as plastic particles less than 5 mm. MPs have become a major environmental pollutant and it is originating from the breakdown of larger plastic waste. This article aims to explore MPs exposure to human health, particularly its potential effects during early developmental years. Studies reveal that MPs exposure begins via intra-uterine route, where MPs were detected in the placenta, amniotic fluid, umbilical cord, fetal membranes, and umbilical vein blood. As infants developed, the MPs exposure continued via breast milk, milk storage bags, formula, feeding bottles, and even from pacifiers. During early childhood, exposure routes can be from 3 different routes, including dermal contact (clothing, childcare products), ingestion (bottled milk, school dust, playground sand, sugar, salt), and inhalation (toy blocks, play mats, indoor air). The review also highlights the potential health risks to vital organs and systems from prenatal as well as postnatal MPs exposure in in vivo studies. These includes the optical, neurological, cardiovascular, pulmonary, hepatic, urinary, digestive, skeletal, lymphatic and reproductive systems. Given their small size and potential toxicity, MPs may disrupt these important developmental processes, leading to long-term health consequences. This article explores the route of MPs exposure with the potential severity and health impacts of those exposure, especially for fetuses, infants, and children. By doing so, it aims to identify any missing knowledge in this area. This research will serve as a foundation for designing future studies that identify health risks in generations exposed to MPs from a very young age.
微塑料(MPs)被定义为小于5 mm的塑料颗粒。MPs已经成为一种主要的环境污染物,它起源于大型塑料废物的分解。本文旨在探讨MPs暴露对人体健康的影响,特别是其在早期发育时期的潜在影响。研究表明,MPs暴露始于子宫内途径,在胎盘、羊水、脐带、胎膜和脐静脉血液中检测到MPs。随着婴儿的发育,多磺酸粘多糖会通过母乳、储奶袋、配方奶粉、奶瓶甚至安抚奶嘴继续接触。在幼儿期,接触途径可来自3种不同途径,包括皮肤接触(衣服、儿童保育产品)、摄入(瓶装牛奶、学校灰尘、操场沙子、糖、盐)和吸入(玩具积木、游戏垫、室内空气)。该综述还强调了体内研究中产前和产后MPs暴露对重要器官和系统的潜在健康风险。这些包括光学系统、神经系统、心血管系统、肺系统、肝系统、泌尿系统、消化系统、骨骼系统、淋巴系统和生殖系统。考虑到它们的小体积和潜在的毒性,MPs可能会破坏这些重要的发育过程,导致长期的健康后果。本文探讨了MPs暴露的途径以及这些暴露的潜在严重性和健康影响,特别是对胎儿、婴儿和儿童。通过这样做,它旨在识别该领域中任何缺失的知识。这项研究将作为设计未来研究的基础,以确定从很小的时候就暴露于MPs的几代人的健康风险。
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引用次数: 0
Potentially toxic elements in the Bangladeshi diet: An assessment of plant-based foods from a rural market 孟加拉国饮食中的潜在有毒元素:对农村市场植物性食品的评估
Q1 Environmental Science Pub Date : 2025-10-14 DOI: 10.1016/j.toxrep.2025.102142
Shamim Al Mamun , Jannatara Ferdush , Alisha Islam , Sowmik Das Sowmya , Brett H. Robinson , Ismail Rahman
Contamination of staple foods with potentially toxic elements (PTEs) poses significant health concerns. Following reports of elevated concentrations of cadmium (Cd), chromium (Cr), nickel (Ni), and lead (Pb) in Bangladeshi soils, we aimed to determine the concentrations of these elements in commonly consumed vegetables (n = 10 species) and rice (n = 5 varieties) collected from markets in the Jamalpur district, Bangladesh, a representative rural market, to evaluate the associated human health risks. Mean PTE concentrations in vegetables frequently exceeded FAO/WHO food safety standards (FSS). All rice samples exceeded the FSS limits for Cd, Ni, and Pb, with 80 % exceeding the Cr limits. Health risks were calculated using estimated daily intake (EDI), target hazard quotient (THQ), hazard index (HI), and target carcinogenic risk (TCR). While cumulative non-carcinogenic risks (HI < 1) were within acceptable levels for both adults and children, the EDI values for Cd, Ni, and Pb in adults, as well as Cd and Cr in children, exceeded their respective tolerable daily intakes (TDI). The TCR for Cd and Cr exceeded the USEPA threshold (10−4) for both age groups, indicating significant carcinogenic risks. Principal component analysis revealed that Cd, Ni, and Pb likely originated from common sources such as industrial emissions and contaminated irrigation water, while Cr appeared to stem from distinct inputs, possibly agrochemicals or textile-related activities. These findings indicate potential health risks, including carcinogenic effects, from dietary PTE exposure in Jamalpur. The results suggest that similar rural regions may benefit from source control, rigorous monitoring, and regulatory interventions to ensure food safety.
含有潜在有毒元素(pte)的主食污染构成了重大的健康问题。在孟加拉国土壤中镉(Cd)、铬(Cr)、镍(Ni)和铅(Pb)浓度升高的报告之后,我们旨在确定从孟加拉国贾马尔普尔地区(一个具有代表性的农村市场)的市场收集的常见食用蔬菜( = 10种)和大米( = 5种)中这些元素的浓度,以评估相关的人类健康风险。蔬菜中PTE的平均浓度经常超过粮农组织/世卫组织的食品安全标准。所有样品的Cd、Ni和Pb均超过FSS限值,其中Cr超标80% %。使用估计每日摄入量(EDI)、目标危害商(THQ)、危害指数(HI)和目标致癌风险(TCR)计算健康风险。虽然累积非致癌风险(HI < 1)在成人和儿童的可接受水平内,但成人中Cd、Ni和Pb的EDI值,以及儿童中Cd和Cr的EDI值,都超过了各自的每日可耐受摄入量(TDI)。两个年龄组中Cd和Cr的TCR均超过USEPA阈值(10−4),表明存在显著的致癌风险。主成分分析表明,Cd、Ni和Pb可能来自工业排放和受污染的灌溉用水等共同来源,而Cr则可能来自不同的投入,可能是农药或与纺织相关的活动。这些发现表明,在贾马尔普尔,从饮食中接触PTE可能存在健康风险,包括致癌效应。结果表明,类似的农村地区可以从源头控制、严格监测和监管干预措施中受益,以确保食品安全。
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引用次数: 0
Acute toxicity of arsenate and arsenite in two scleractinian coral species: Acropora cervicornis and Orbicella faveolata 砷酸盐和亚砷酸盐对两种硬核珊瑚的急性毒性研究:颈角Acropora cervicornis和faveolata Orbicella
Q1 Environmental Science Pub Date : 2025-10-13 DOI: 10.1016/j.toxrep.2025.102141
Cailey E. Dorman , Dimitrios G. Giarikos , Amy C. Hirons , Carys L. Mitchelmore , D. Abigail Renegar
Inorganic arsenic, specifically arsenate [As(V)] and arsenite [As(III)], disrupts physiological and biochemical processes in marine organisms, yet their specific impacts on coral reef species remain largely unstudied. This study is the first to assess the acute and subacute toxicity of arsenate [As(V)] and arsenite [As(III)] on two threatened scleractinian coral species, Acropora cervicornis and Orbicella faveolata. Using four 96-h static-renewal assays, corals were exposed to six treatments: five concentrations and a negative control with all concentrations being analytically verified. Toxicity was evaluated through three endpoints: mortality (LC50), coral condition (EC50), and photosynthetic efficiency (IC50). The LC50s were found to be 0.0365 mg L−1 As(V) and 0.111 mg L−1 As(III) for A. cervicornis and 0.315 mg L−1 As(V) and 0.235 mg L−1 As(III) for O. faveolata. Both species showed significant adverse effects across all subacute endpoints, with Orbicella faveolata significantly more sensitive to As(III), whereas A. cervicornis showed greater sensitivity to As(V). This challenges the prevailing assumption that As(III) is universally more toxic to marine taxa. Species sensitivity distributions found that the LC50 values for these corals were lower than previously reported marine organism’s LC50s, highlighting the heightened vulnerability of coral. These findings provide critical data for refining sediment quality guidelines and improving ecological risk assessments in arsenic-impacted reef environments.
无机砷,特别是砷酸盐[As(V)]和亚砷酸盐[As(III)],破坏海洋生物的生理和生化过程,但它们对珊瑚礁物种的具体影响在很大程度上尚未得到研究。本研究首次评估了砷酸盐[As(V)]和亚砷酸盐[As(III)]对两种濒危硬核珊瑚(Acropora cervicornis和Orbicella faveolata)的急性和亚急性毒性。使用四种96小时静态更新试验,珊瑚暴露于六种处理:五种浓度和一种阴性对照,所有浓度都经过分析验证。毒性通过三个终点进行评估:死亡率(LC50)、珊瑚状况(EC50)和光合效率(IC50)。结果表明,颈喙草的lc50分别为0.0365 mg L−1 As(V)和0.111 mg L−1 As(III),黄叶菊的lc50分别为0.315 mg L−1 As(V)和0.235 mg L−1 As(III)。这两种物种在所有亚急性终点均表现出显著的不良反应,黄豆环虫对As(III)明显更敏感,而颈角拟虫对As(V)更敏感。这挑战了普遍认为As(III)对海洋生物的毒性更大的假设。物种敏感性分布发现,这些珊瑚的LC50值低于先前报道的海洋生物的LC50值,突出了珊瑚的脆弱性。这些发现为完善沉积物质量指南和改善砷影响珊瑚礁环境的生态风险评估提供了关键数据。
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