Toxicity

毒性
  • 文章类型: Journal Article
    取代的对苯二胺(PPD),一类抗氧化剂,已被广泛用于延长橡胶制品的使用寿命,如轮胎和管道。在使用过程中,PPD将产生它们的醌衍生物(PPD-Qs)。近年来,已经在全球环境中检测到PPD和PPD-Qs。其中,N-(1,3-二甲基丁基)-N'-苯基-对苯二胺醌(6PPD-Q),N-(1,3-二甲基丁基)-N'-苯基-对苯二胺(6PPD)的氧化产物,已被确认对银鲑鱼有剧毒,50%的致死浓度(LC50)为95ng/L,强调它是一种备受关注的新兴污染物。这篇综述总结了物理化学性质,全球环境分布,生物可及性,潜在毒性,人类暴露风险,以及与PPD和PPD-Qs相关的绿色措施。这些化学物质表现出亲脂性,生物累积潜力,和差的水稳定性。它们在水中被发现,空气,灰尘,土壤,和世界各地的沉积物,表明它们作为新兴污染物的重要性。值得注意的是,目前的研究已经确定了电子废物,例如废弃的电线和电缆,作为PPD和PPD-Qs的不可忽略的来源,除了轮胎磨损。PPD和PPD-Qs在水生生物和哺乳动物中表现出很强的生物蓄积性,随着食物网内生物放大的趋势,对人类健康构成威胁。现有的毒性数据表明,PPD和PPD-Qs对水生生物有负面影响,哺乳动物,和无脊椎动物。急性暴露会导致死亡和急性损伤,虽然长期接触会造成一系列不良影响,包括生长和发育毒性,生殖毒性,神经毒性,肠道毒性,和多器官损伤。本文讨论了当前的研究空白,并提出了更好地理解这种情况的建议,行为,毒性,以及PPD和PPD-Qs的环境暴露风险。
    Substituted p-phenylenediamines (PPDs), a class of antioxidants, have been widely used to extend the lifespan of rubber products, such as tires and pipes. During use, PPDs will generate their quinone derivatives (PPD-Qs). In recent years, PPDs and PPD-Qs have been detected in the global environment. Among them, N-(1,3-dimethylbutyl)-N\'-phenyl-p-phenylenediamine quinone (6PPD-Q), the oxidation product of N-(1,3-dimethylbutyl)-N\'-phenyl-p-phenylenediamine (6PPD), has been identified as highly toxic to coho salmon, with the lethal concentration of 50 % (LC50) being 95 ng/L, highlighting it as an emerging pollutant of great concern. This review summarizes the physicochemical properties, global environmental distribution, bioaccessibility, potential toxicity, human exposure risk, and green measures associated with PPDs and PPD-Qs. These chemicals exhibit lipophilicity, bioaccumulation potential, and poor aqueous stability. They have been found in water, air, dust, soil, and sediment worldwide, indicating their significance as emerging pollutants. Notably, current studies have identified electronic waste, such as discarded wires and cables, as a non-negligible source of PPDs and PPD-Qs, in addition to tire wear. PPDs and PPD-Qs exhibit strong bioaccumulation in aquatic organisms and mammals, with a tendency for biomagnification within the food web, posing health threats to humans. Available toxicity data indicate that PPDs and PPD-Qs have negative effects on aquatic organisms, mammals, and invertebrates. Acute exposure leads to death and acute damage, while long-term exposure can cause a series of adverse effects, including growth and development toxicity, reproductive toxicity, neurotoxicity, intestinal toxicity, and multi-organ damage. This paper discusses current research gaps and offers recommendations to understand better the occurrence, behavior, toxicity, and environmental exposure risks of PPDs and PPD-Qs.
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  • 文章类型: Journal Article
    工业和城市固体废物的混合燃烧已成为最有前途的处置技术,然而,由于废物的复杂性,其对未知污染物产生的影响很少被揭示。因此,在650t/d的焚烧炉中设计了六批大型工程实验,克服了实验室测试的不真实性和偏差。在粉煤灰中筛选953-1772种非靶向化合物。以共同燃烧的影响为目标,创新地集成了伪成分矩阵模型,以从分为生物质和塑料的复杂废物中定量提取9种成分。因此,影响在八个维度上进行了评估,涵盖分子特征和毒性。与生物质假组分共燃的效果不明显。然而,与高比例的塑料伪成分共燃导致更高的潜在风险,显著促进不饱和烃的形成,高度不饱和化合物(DBE≥15),环状化合物占19%-49%,17%-31%,7%-27%,分别。尤其是,与高比例的PET塑料假成分混合会产生更多的污染物。独特的2级I毒物,溴甲基苯和苯并呋喃-2-甲醛,以及4种II级毒物,被锁上了,在以前的燃烧中没有受到关注。结果突出了高比例塑料共燃烧期间的风险,这可以通过调整源废物以实现健康的共燃烧来帮助减少污染。
    Co-combustion of industrial and municipal solid wastes has emerged as the most promising disposal technology, yet its effect on unknown contaminants generation remains rarely revealed due to waste complexity. Hence, six batches of large-scale engineering experiments were designed in an incinerator of 650 t/d, which overcame the inauthenticity and deviation of laboratory tests. 953-1772 non-targeted compounds were screened in fly ash. Targeting the impact of co-combustion, a pseudo-component matrix model was innovatively integrated to quantitatively extract nine components from complex wastes grouped into biomass and plastic. Thus, the influence was evaluated across eight dimensions, covering molecular characteristics and toxicity. The effect of co-combustion with biomass pseudo-components was insignificant. However, co-combustion with high ratios of plastic pseudo-components induced higher potential risks, significantly promoting the formation of unsaturated hydrocarbons, highly unsaturated compounds (DBE≥15), and cyclic compounds by 19 %- 49 %, 17 %- 31 %, and 7 %- 27 %, respectively. Especially, blending with high ratios of PET plastic pseudo-components produced more species of contaminants. Unique 2 Level I toxicants, bromomethyl benzene and benzofuran-2-carbaldehyde, as well as 4 Level II toxicants, were locked, receiving no concern in previous combustion. The results highlighted risks during high proportion plastics co-combustion, which can help pollution reduction by tuning source wastes to enable healthy co-combustion.
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  • 文章类型: Journal Article
    拟除虫菊酯是合成的有机杀虫剂。溴氰菊酯,作为拟除虫菊酯之一,对害虫和寄生虫具有很高的杀虫活性,对哺乳动物的毒性较小,并广泛应用于世界各地的城市和城市地区。进入自然环境后,溴氰菊酯在固体之间循环,液相和气相并通过食物链进入生物体,构成重大健康风险。越来越多的证据表明溴氰菊酯对多种生物具有不同程度的毒性。这篇综述总结了世界范围内对溴氰菊酯在不同介质中残留的研究,并发现溴氰菊酯在一系列环境(包括土壤,水,沉积物,和空气)和生物。此外,溴氰菊酯的代谢,包括代谢产物和酶,进行了讨论。本文综述了溴氰菊酯及其代谢产物的毒性机制。包括神经毒性,免疫毒性,内分泌干扰毒性,生殖毒性,肝肾毒性。旨在为溴氰菊酯的生态安全和人体健康风险评估提供参考。
    Pyrethroids are synthetic organic insecticides. Deltamethrin, as one of the pyrethroids, has high insecticidal activity against pests and parasites and is less toxic to mammals, and is widely used in cities and urban areas worldwide. After entering the natural environment, deltamethrin circulates between solid, liquid and gas phases and enters organisms through the food chain, posing significant health risks. Increasing evidence has shown that deltamethrin has varying degrees of toxicity to a variety of organisms. This review summarized worldwide studies of deltamethrin residues in different media and found that deltamethrin is widely detected in a range of environments (including soil, water, sediment, and air) and organisms. In addition, the metabolism of deltamethrin, including metabolites and enzymes, was discussed. This review shed the mechanism of toxicity of deltamethrin and its metabolites, including neurotoxicity, immunotoxicity, endocrine disruption toxicity, reproductive toxicity, hepatorenal toxicity. This review is aim to provide reference for the ecological security and human health risk assessment of deltamethrin.
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  • 文章类型: Journal Article
    背景:陈皮(CRP),在中国被称为陈皮,是最常用的理气药。作为一种传统医学,CRP已广泛应用于临床治疗恶心,呕吐,咳嗽和痰数千年。主要分布在广东,四川,中国的福建和浙江。由于其使用频率高,许多学者对它及其含有的相关化学成分进行了大量的研究。在这次审查中,植物化学的研究进展,药理学,总结了CRP的药代动力学和毒理学。
    目的:本综述旨在梳理提取和纯化的方法,药理活性和作用机制,CRP中化学成分的药代动力学和毒理学,为今后CRP及相关化学成分的研究提出方向和挑战。
    方法:从中国国家知识基础设施收集了有效和全面的相关信息,WebofScience,PubMed等等。
    结果:CRP含有多种化合物,哪些萜烯,黄酮类化合物和生物碱是主要成分,它们也是发挥药理作用的主要生物活性成分。黄酮类化合物和萜烯通过水性和酒精提取方法提取和纯化,超声波和微波辅助提取,以便用更少的资源获得更高的产量。药理学研究表明,CRP具有多种高活性的化学成分和广泛的药理活性,包括抗肿瘤,抗炎,免疫调节,保肝,治疗心血管相关疾病,抗氧化剂,抗菌,和神经保护作用。
    结论:CRP的化学成分多种多样,具有多种生物活性和应用前景。然而,CRP的药理活性主要依赖于其化学成分的作用,但是化学成分的结构与生物效应之间的关系尚未得到彻底的研究,因此,结构-活动关系是一个迫切需要阐明的问题。此外,可进一步深化相关成分的药代动力学研究,拓展药理作用与中医证候的相关性研究,确保CRP人用的有效性和合理性。
    BACKGROUND: Citri Reticulatae Pericarpium (CRP), known as Chen Pi in China, is the most commonly used medicine for regulating qi. As a traditional medicine, CRP has been extensively used in the clinical treatment of nausea, vomiting, cough and phlegm for thousands of years. It is mainly distributed in Guangdong, Sichuan, Fujian and Zhejiang in China. Due to its high frequency of use, many scholars have conducted a lot of research on it and the related chemical constituents it contains. In this review, the research progress on phytochemistry, pharmacology, pharmacokinetics and toxicology of CRP are summarized.
    OBJECTIVE: The review aims to sort out the methods of extraction and purification, pharmacological activities and mechanisms of action, pharmacokinetics and toxicology of the chemical constituents in CRP, in order to elaborate the future research directions and challenges for the study of CRP and related chemical constituents.
    METHODS: Valid and comprehensive relevant information was collected from China National Knowledge Infrastructure, Web of Science, PubMed and so on.
    RESULTS: CRP contains a variety of compounds, of which terpenes, flavonoids and alkaloids are the main components, and they are also the primary bioactive components that play a pharmacological role. Flavonoids and terpenes are extracted and purified by aqueous and alcoholic extraction methods, assisted by ultrasonic and microwave extraction, in order to achieve higher yields with less resources. Pharmacological studies have shown that CRP possesses a variety of highly active chemical components and a wide range of pharmacological activities, including anti-tumor, anti-inflammatory, immunomodulatory, hepatoprotective, therapeutic for cardiovascular-related disorders, antioxidant, antibacterial, and neuroprotective effects.
    CONCLUSIONS: There is a diversity in the chemical compositions of CRP, which have multiple biological activities and promising applications. However, the pharmacological activities of CRP are mainly dependent on the action of its chemical components, but the relationship between the structure of chemical components and the biological effects has not been thoroughly investigated, and therefore, the structure-activity relationship is an issue that needs to be elucidated urgently. In addition, the pharmacokinetic studies of the relevant components can be further deepened and the correlation studies between pharmacological effects and syndromes of TCM can be expanded to ensure the effectiveness and rationality of CRP for human use.
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  • 文章类型: Journal Article
    本文旨在强调自然生态系统中各种新兴污染物(EC)混合物的发生,并强调了由于不受管制地释放到土壤和水中而引起的主要关注。以及它们对人类健康的影响。新兴的污染物混合物,包括药品,个人护理产品,二恶英,多氯联苯,杀虫剂,抗生素,杀生物剂,表面活性剂,邻苯二甲酸酯,肠道病毒,和微塑料(MPs),被认为是具有严重影响的有毒污染物。MP在将污染物输送到水生和陆地生态系统中起着至关重要的作用,因为它们与土壤和水环境的各个组成部分相互作用。这篇综述总结了主要的新兴污染物(ECs),比如甲氧苄啶,双氯芬酸,磺胺甲恶唑,和17α-炔雌醇,对公众健康构成严重威胁,并导致抗菌素耐药性。在解决人类健康问题和补救技术方面,这篇综述严格评估了从复杂基质中去除ECs的常规方法。周围环境的不同物理化学性质促进了ECs向沉积物和其他有机相的分配。导致致癌,致畸,和雌激素效应通过芳香烃受体介导的活性催化作用和机制。ECs混合物络合的主动毒性,在某种程度上,尚未确定的EC的环境混合物代表了当前文献中的一个盲点,需要概念框架来评估单个组分和混合物的毒性和风险。最后,这篇综述最后对未来的范围进行了深入的探索,知识差距,和挑战,强调需要齐心协力管理ECs和其他有机污染物。
    This paper aims to emphasize the occurrence of various emerging contaminant (EC) mixtures in natural ecosystems and highlights the primary concern arising from the unregulated release into soil and water, along with their impacts on human health. Emerging contaminant mixtures, including pharmaceuticals, personal care products, dioxins, polychlorinated biphenyls, pesticides, antibiotics, biocides, surfactants, phthalates, enteric viruses, and microplastics (MPs), are considered toxic contaminants with grave implications. MPs play a crucial role in transporting pollutants to aquatic and terrestrial ecosystems as they interact with the various components of the soil and water environments. This review summarizes that major emerging contaminants (ECs), like trimethoprim, diclofenac, sulfamethoxazole, and 17α-Ethinylestradiol, pose serious threats to public health and contribute to antimicrobial resistance. In addressing human health concerns and remediation techniques, this review critically evaluates conventional methods for removing ECs from complex matrices. The diverse physiochemical properties of surrounding environments facilitate the partitioning of ECs into sediments and other organic phases, resulting in carcinogenic, teratogenic, and estrogenic effects through active catalytic interactions and mechanisms mediated by aryl hydrocarbon receptors. The proactive toxicity of ECs mixture complexation and, in part, the yet-to-be-identified environmental mixtures of ECs represent a blind spot in current literature, necessitating conceptual frameworks for assessing the toxicity and risks with individual components and mixtures. Lastly, this review concludes with an in-depth exploration of future scopes, knowledge gaps, and challenges, emphasizing the need for a concerted effort in managing ECs and other organic pollutants.
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  • 文章类型: Journal Article
    饮用水分配系统(DWDS)中的金属对消毒副产物(DBPs)的命运起着重要作用。它们可以通过几种机制增加DBPs的形成,例如提高活性卤素物质(RHS)的比例,通过络合催化天然有机物(NOM)和RHS之间的反应,或通过增加NOM转化为DBP前体。这篇综述全面总结了这些复杂的过程,专注于最重要的金属(铜,铁,DWDS中的锰)及其对各种DBPs的影响。它将分散的“金属DBPs”实验结果组织成一个易于访问的内容结构,并展示了它们潜在的共同或独特机制。此外,分析了这些研究成果的实际应用方向,包括DBP在金属影响下的毒性变化以及DBP模型研究中通过金属的引入可能增强的泛化性。总的来说,这篇综述表明,DWDS中的金属环境是影响自来水中DBP水平的关键因素。
    Metals in the drinking water distribution system (DWDS) play an important role on the fate of disinfection by-products (DBPs). They can increase the formation of DBPs through several mechanisms, such as enhancing the proportion of reactive halogen species (RHS), catalysing the reaction between natural organic matter (NOM) and RHS through complexation, or by increasing the conversion of NOM into DBP precursors. This review comprehensively summarizes these complex processes, focusing on the most important metals (copper, iron, manganese) in DWDS and their impact on various DBPs. It organizes the dispersed \'metals-DBPs\' experimental results into an easily accessible content structure and presents their underlying common or unique mechanisms. Furthermore, the practically valuable application directions of these research findings were analysed, including the toxicity changes of DBPs in DWDS under the influence of metals and the potential enhancement of generalization in DBP model research by the introduction of metals. Overall, this review revealed that the metal environment within DWDS is a crucial factor influencing DBP levels in tap water.
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  • 文章类型: Journal Article
    钨(W)是一种新兴的重金属污染物,然而,关于W污染的生物标志物和敏感生物标志物的研究仍然很少。
    在这项研究中,选择芹菜和辣椒作为研究对象,并在具有五种不同W水平的溶液中进行暴露培养。系统分析了W对这两种植物的生理生化毒性。探索了利用芹菜和辣椒作为W污染生物微生物的可行性,并筛选了指示性生物标志物。
    结果表明,W可以抑制植物的根长,射击高度,和鲜重,同时促进膜脂过氧化。此外,W增强了超氧化物歧化酶(SOD)的活性,过氧化氢酶(CAT),过氧化物酶(POD),和总抗氧化能力(TAOC)以抵抗氧化损伤。从生理的角度来看,胡椒显示出作为W污染的生物监测器的潜力。生化指标提示SOD可作为芹菜中W的敏感生物标志物,而TAOC和POD更适合辣椒的根和叶。总之,我们的研究调查了W对芹菜和辣椒的毒性作用,有助于了解W的环境毒性。此外,它为选择生物监测生物和W污染的敏感生物标志物提供了见解。
    UNASSIGNED: Tungsten (W) is an emerging heavy metal pollutant, yet research remains scarce on the biomonitor and sensitive biomarkers for W contamination.
    UNASSIGNED: In this study, celery and pepper were chosen as study subjects and subjected to exposure cultivation in solutions with five different levels of W. The physiological and biochemical toxicities of W on these two plants were systematically analyzed. The feasibility of utilizing celery and pepper as biomonitor organisms for W contamination was explored and indicative biomarkers were screened.
    UNASSIGNED: The results indicated that W could inhibit plants\' root length, shoot height, and fresh weight while concurrently promoting membrane lipid peroxidation. Additionally, W enhanced the activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and total antioxidant capacity (TAOC) to counteract oxidative damage. From a physiological perspective, pepper exhibited potential as a biomonitor for W contamination. Biochemical indicators suggested that SOD could serve as a sensitive biomarker for W in celery, while TAOC and POD were more suitable for the roots and leaves of pepper. In conclusion, our study investigated the toxic effects of W on celery and pepper, contributing to the understanding of W\'s environmental toxicity. Furthermore, it provided insights for selecting biomonitor organisms and sensitive biomarkers for W contamination.
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  • 文章类型: Journal Article
    为了提高轮胎的耐用性,抗氧剂N-(1,3-二甲基丁基)-N'-苯基-对苯二胺(6PPD)用于橡胶,但是当暴露于臭氧(O3)等氧化剂时,它会转化为有毒的6PPD醌(6PPD-Q),引起生态问题。这篇综述综合了现有的数据来评估这种转变,生物利用度,以及两种轮胎衍生污染物6PPD和6PPD-Q的潜在危害。分析了将轮胎和塑料等废料重新用于有价值产品的不同热方法的比较分析。这些方法揭示了热解和催化转化过程的各个方面,为优化废物价值和减轻环境影响提供有价值的观点。此外,我们已经检查了轮胎制造中使用的化学品的生物利用度和潜在危害,基于这篇综述中包含的文献。这些化学物质的生物利用度,特别是6PPD到6PPD-Q的转化,造成重大生态风险。6PPD-Q在水生环境中具有很高的生物利用度,表明其潜在的广泛生态危害。6PPD-Q在环境中的持久性和移动性,以及它的毒理学效应,强调迫切需要持续监测和制定有效的缓解战略,以减少其对人类健康和生态系统的影响。未来的研究应该集中在了解低水平暴露于这些化合物对陆地和水生生态系统的长期影响。以及食物链中生物积累的潜力。此外,这篇综述概述了知识差距,建议进一步研究轮胎衍生污染物对生物体的毒性以及对人类和生态系统的健康影响。
    To enhance tire durability, the antioxidant N-(1,3-dimethylbutyl)-N\'-phenyl-p-phenylenediamine (6PPD) is used in rubber, but it converts into the toxic 6PPD quinone (6PPD-Q) when exposed to oxidants like ozone (O3), causing ecological concerns. This review synthesizes the existing data to assess the transformation, bioavailability, and potential hazards of two tire-derived pollutants 6PPD and 6PPD-Q. The comparative analysis of different thermal methods utilized in repurposing waste materials like tires and plastics into valuable products are analyzed. These methods shed light on the aspects of pyrolysis and catalytic conversion processes, providing valuable perspectives into optimizing the waste valorization and mitigating environmental impacts. Furthermore, we have examined the bioavailability and potential hazards of chemicals used in tire manufacturing, based on the literature included in this review. The bioavailability of these chemicals, particularly the transformation of 6PPD to 6PPD-Q, poses significant ecological risks. 6PPD-Q is highly bioavailable in aquatic environments, indicating its potential for widespread ecological harm. The persistence and mobility of 6PPD-Q in the environment, along with its toxicological effects, highlight the critical need for ongoing monitoring and the development of effective mitigation strategies to reduce its impact on both human health and ecosystem. Future research should focus on understanding the chronic effects of low-level exposure to these compounds on both terrestrial and aquatic ecosystems, as well as the potential for bioaccumulation in the food chain. Additionally, this review outlines the knowledge gaps, recommending further research into the toxicity of tire-derived pollutants in organisms and the health implications for humans and ecosystems.
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  • 文章类型: Journal Article
    了解重金属(HM)耐受机制对于改善金属污染土壤中植物的生长至关重要。为了评价芸苔属植物对铅(Pb)的耐性机制,使用比较蛋白质组学研究。用0、3、30和300mg/L的不同浓度的Pb(NO3)2处理了13天龄的B.junea和B.napus幼苗。在300mg/L的Pb(NO3)2浓度下,B.napus生长显著下降,而芽孢杆菌保持与对照相似的正常生长。甘蓝型油菜根和芽中的铅积累也比甘蓝型油菜高。根的无凝胶蛋白质组分析显示,在芥菜芽孢杆菌和油菜芽孢杆菌中,共有68和37种差异丰富的蛋白质(DAP)。300mg/L铅暴露后。这些蛋白质中的大多数与蛋白质降解有关,细胞呼吸,和酶分类。上调的RPT2和四吡咯生物合成途径相关蛋白维持双歧杆菌的细胞稳态和光合速率。在55个常见的DAP中,铅暴露后,S-腺苷甲硫氨酸和TCA循环蛋白在结球芽孢杆菌中上调,在甘蓝杆菌中下调。此外,较高的氧化应激也降低了甘蓝型油菜的抗氧化酶活性。目前的发现表明,结球芽孢杆菌比欧洲油菜更耐铅,可能是由于参与蛋白质再循环的蛋白质的上调,降解,四吡咯生物合成途径。
    Understanding the heavy metals (HMs) tolerance mechanism is crucial for improving plant growth in metal-contaminated soil. In order to evaluate the lead (Pb) tolerance mechanism in Brassica species, a comparative proteomic study was used. Thirteen-day-old seedlings of B. juncea and B. napus were treated with different Pb(NO3)2 concentrations at 0, 3, 30, and 300 mg/L. Under 300 mg/L Pb(NO3)2 concentration, B. napus growth was significantly decreased, while B. juncea maintained normal growth similar to the control. The Pb accumulation was also higher in B. napus root and shoot compared to B. juncea. Gel-free proteomic analysis of roots revealed a total of 68 and 37 differentially abundant proteins (DAPs) in B. juncea and B. napus-specifically, after 300 mg/L Pb exposure. The majority of these proteins are associated with protein degradation, cellular respiration, and enzyme classification. The upregulated RPT2 and tetrapyrrole biosynthesis pathway-associated proteins maintain the cellular homeostasis and photosynthetic rate in B. juncea. Among the 55 common DAPs, S-adenosyl methionine and TCA cycle proteins were upregulated in B. juncea and down-regulated in B. napus after Pb exposure. Furthermore, higher oxidative stress also reduced the antioxidant enzyme activity in B. napus. The current finding suggests that B. juncea is more Pb tolerant than B. napus, possibly due to the upregulation of proteins involved in protein recycling, degradation, and tetrapyrrole biosynthesis pathway.
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  • 文章类型: Journal Article
    依托咪酯是一种全身麻醉药,具有良好的血流动力学稳定性,没有明显的心血管或呼吸抑制。尽管已经报道了这种药物的几种剂型,在临床实践中,制剂类型非常有限,这种中枢神经系统(CNS)药物的脑靶向制剂很少报道。此外,关于生物相容性的研究,毒性,依托咪酯制剂在体内的麻醉效果不足。本研究旨在开发乳铁蛋白修饰的脂质体依托咪酯(Eto-lip-LF),以增强药物在大脑中的分布并改善麻醉效果。Eto-lip-LF具有良好的储存稳定性和静脉注射血液相容性。与不含乳铁蛋白的脂质体相比,乳铁蛋白修饰的脂质体在体内脑靶向能力显著增强,这可能是通过转铁蛋白与大脑中高度分布的转铁蛋白和乳铁蛋白受体的结合来实现的。Eto-lip-LF的治疗指数约为25.3,高于许多其他全身麻醉药。此外,与市售依托咪酯乳剂相比,Eto-lip-LF能较好地实现全身麻醉的快速起效和麻醉的快速恢复,可能是由于增强了对大脑的药物输送。上述结果表明,这种乳铁蛋白修饰的脂质体依托咪酯有可能成为临床全身麻醉的替代制剂。
    Etomidate is a general anesthetic that has shown good hemodynamic stability without significant cardiovascular or respiratory depression. Despite several kinds of dosage forms having been reported for this drug, formulation types are very limited in clinical practice, and brain-targeted formulations for this central nervous system (CNS) drug have been rarely reported. Moreover, studies on the biocompatibility, toxicity, and anesthetic effects of the etomidate preparations in vivo were inadequate. The present study was to develop lactoferrin-modified liposomal etomidate (Eto-lip-LF) for enhanced drug distribution in the brain and improved anesthetic effects. Eto-lip-LF had good stability for storage and hemocompatibility for intravenous injection. Compared with the non-lactoferrin-containing liposomes, the lactoferrin-modified liposomes had notably enhanced brain-targeting ability in vivo, which was probably realized by the binding of transferrin with the transferrin and lactoferrin receptors highly distributed in the brain. Eto-lip-LF had a therapeutic index of about 25.3, higher than that of many other general anesthetics. Moreover, compared with the commercial etomidate emulsion, Eto-lip-LF could better achieve rapid onset of general anesthesia and rapid recovery from anesthesia, probably due to the enhanced drug delivery to the brain. The above results demonstrated the potential of this lactoferrin-modified liposomal etomidate to become an alternative preparation for clinical general anesthesia.
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