纳米银的体内毒性及毒作用机制研究进展

很多研究表明纳米银对机体的消化系统、呼吸系统、生殖系统等多个系统均会产生毒作用,且其毒作用受到多种因素的影响。目前关于纳米银的毒作用机制尚未明确,研究发现纳米银的毒作用机制可能与银离子释放、活性氧自由基产生、氧化应激的发生、炎症反应等有关,最新研究指出纳米银的毒性作用还可能与内质网应激和自噬有关,本文将就纳米银的体内毒性及毒作用机制进行了综述。     

纳米银材料的生物安全性研究进展

纳米银材料被广泛应用到医疗、化工、生物等许多领域,增加了与人类接触的可能性,因此关注其生物安全性是很有必要的。本文对近年来纳米银的抗菌性和生物安全性研究进行了综述。首先分析了纳米银的皮肤毒性、呼吸系统毒性、消化系统毒性和其他组织毒性,其次分析了体外细胞毒性和细胞内纳米银与生物大分子相互作用,最后对纳米银材料的人群暴露生物安全性及纳米银与银离子毒性关系进行了探讨。本文旨在为纳米银的毒性作用机制研究提供参考,为建立标准的纳米银安全性评价体系提供依据。     

纳米银复合材料与抗生素的联合抗菌性能及相关机制研究

抗生素的滥用导致细菌耐药问题日益严重,人类迫切需要开发出新的抗菌药物以减少细菌耐药问题。基于纳米银制备而成的纳米银复合材料在兼顾纳米银抗菌性能的同时不仅能够克服单一纳米银释放速度快、不稳定等缺点,还能缓解细菌耐药的问题,因此被认为是一类具有广泛应用前景的新型抗菌剂。已有研究表明,单一纳米银与某些抗生素的联合使用可以达到协同抗菌效果,但目前尚缺乏对纳米银复合材料与抗生素的联合抗菌性能及机制的研究。本文首先制备出3种不同结构的纳米银复合材料,包括二氧化硅-聚多巴胺-纳米银复合材料(SiO_2-PD-AgNPs)、纳米银@二氧化硅复合材料(AgNPs@SiO_2)和纳米银@二氧化硅-聚多巴胺-纳米银复合材料(AgNPs@SiO_2-PD-AgNPs)。随后测定了纳米银复合材料对大肠杆菌(Escherichia coli, E. coli)和枯草芽孢杆菌(Bacillus subtilis, B. subtilis)的单一毒性效应。结果显示,AgNPs@SiO_2-PD-AgNPs复合材料对2种菌的单一毒性均大于其余2种纳米银复合材料。因此,笔者以AgNPs@SiO_2-PD-AgNPs作为代表,测定了纳米银复合材料与硫酸卡那霉素(kanamycin sulfate, KS)/盐酸土霉素(oxytetracycline hydrochloride, OH)的二元联合抗菌性能,发现AgNPs@SiO_2-PD-AgNPs与KS联合可以对E. coli产生协同效应。协同效应产生的主要原因可能是:AgNPs@SiO_2-PD-AgNPs释放出的纳米银会和KS发生键合反应生成KS-纳米银复合物,导致纳米银释放出大量的Ag+增加了细胞膜的通透性,从而使得进入细菌内的Ag~+和KS比单独作用时进入胞内的抗菌剂增多,产生更强的抗菌性能,从而表现出协同抗菌效应。本研究基于新型纳米银复合材料与抗生素的联合抗菌性能实验探究了纳米银复合材料与特定抗生素联合用药的最佳组合和相关机制,为今后开发新型抗菌材料提供了新思路并为相关联合用药提供参考。     

抗生素和纳米银对大肠杆菌的联合毒性和抗性突变诱导效应

抗生素和纳米银因在各自领域的大量应用而不可避免地进入环境中，对生态环境尤其是微生物群体构成联合暴露的风险，但是二者对细菌生长和耐药性的联合作用，目前受到的关注较少.本研究测定了两种抗生素（四环素和氯霉素）以及纳米银（10—15 nm）对大肠杆菌的联合毒性及对细菌抗性突变的诱导作用，并对相关机制进行了初步探讨.结果表明，抗生素和纳米银对细菌的联合毒性呈现协同效应，但是二者联合作用下细菌对利福平的抗性突变频率显著降低. DNA测序和分子对接结果表明，编码利福平靶标蛋白的rpoB基因发生点突变，导致突变后的靶蛋白与利福平的结合能降低.同时，qPCR结果表明抗生素和纳米银联合作用时，细菌胞内rpoS、dinB和mutS等基因表达显著上调，可能是抗性突变频率在联合作用下降低的主要原因.本研究揭示了抗生素和纳米银联合作用对细菌抗性突变的影响，有利于全面认识二者联合暴露的环境和健康风险.     

通讯

纳米银通过结合RNA聚合酶抑制红系前体细胞RNA的转录由于其广谱的抗菌活性,纳米银在日常生活和医药卫生中得到广泛的应用.纳米银的大量生产和使用将导致其在生产、运输、使用和排放等环节释放入环境,其潜在的环境与健康风险已日益受到关注.研究发现,纳米银可以引发呼吸系统(肺)、消化系统(肝脏)、神经系统(神经元)和生殖系统的组织损伤.然而,目前对纳米银毒性效应的分子作用机制尚待深入研究.     

碳纳米管生殖毒性及其毒作用机制研究进展

随着碳纳米管(carbon nanotubes,CNTs)在各个领域应用的增加,人们接触到CNTs的几率也随之增加,越来越多的人开始关注CNTs对于人体是否具有毒性及其毒性的大小,近些年的体内和体外研究显示,CNTs可对生物体(如小鼠、斑马鱼、赤子爱胜蚓等)生殖系统产生毒性并遗传给后代,影响后代生长发育。本综述主要从CNTs种类、官能化和CNTs悬浮液中团聚体尺寸及所含杂质3个方面探讨CNTs的生殖毒性及毒作用机制,以及影响其毒性及毒作用机制的因素,从而为CNTs更加安全有效的应用提供依据。     

纳米银和银离子对斑马鱼胚胎早期生长发育的影响及作用机制

为探究纳米银对水生生物的毒性作用,选取斑马鱼胚胎为受试生物,考察了纳米银对斑马鱼胚胎早期生长发育的影响,同时比较了纳米银与银离子对斑马鱼胚胎的毒性作用和机理。实验将受精后4小时(4 hpf)的斑马鱼胚胎分别暴露于不同浓度的纳米银和银离子溶液中至96 hpf,观察并记录了胚胎的死亡、孵化和畸形等指标。应用吖啶橙(AO)染色实验研究了胚胎暴露之后的细胞凋亡情况,并且应用荧光定量PCR技术分析了相关基因的表达水平。研究结果表明,随着暴露浓度的增加,纳米银和银离子均能导致斑马鱼胚胎的死亡率增加和孵化率降低,并且引起孵化延迟。纳米银和银离子的96 h半数致死浓度(96 h-LC50)分别为11.75 mg·L-1和0.054 mg·L-1。银离子毒性远大于纳米银毒性。暴露的斑马鱼胚胎均表现出体长变短和卵黄囊肿大的畸形。AO染色结果表明,纳米银和银离子处理组胚胎的躯干和卵黄囊部位存在细胞凋亡信号。基因表达分析结果显示,1.93 mg·L-1纳米银显著提高了斑马鱼胚胎caspase9的表达(P0.05),而0.006 mg·L-1的银离子就能显著上调COX-2a(P0.01)和COX-17(P0.05)基因的表达,同时0.036 mg·L-1银离子增加了斑马鱼体内p53基因的表达(P0.05)。以上研究结果说明,纳米银可能通过caspase通路诱导细胞凋亡进而影响斑马鱼胚胎的生长发育;而银离子不但影响氧化系统基因通路,还能通过p53诱导凋亡进而阻滞斑马鱼胚胎的生长发育。     

纳米银的植物毒性研究进展

纳米银因其具备良好的催化、超导性能及杀菌消毒活性,广泛应用于食品加工业及医药等领域,是目前市场上最为常见的金属纳米材料。纳米银的大量生产和应用大大增加了其向环境释放的机会,同时也增加了其对环境及人类健康的潜在风险。植物是生态系统中重要组成部分,纳米银可通过植物积累进入食物链,因此对纳米银的植物毒理学研究尤为重要。纳米银的植物毒性与其被植物体吸收、迁移及转化有关。它可影响植物种子的萌发、苗期的生理生化过程和细胞结构等营养生长,也影响植物的开花、结实等生殖过程,并影响DNA的稳定性。但目前纳米银的毒性是否由银离子引起尚未确定。     

纳米银的迁移转化对环境微生物毒性的影响

纳米银(AgNPs)因其优越的抗菌、导电、催化等性能,被广泛应用于工业领域和日常生活中,成为当前产量和用量最高的纳米材料之一。但纳米银产品在生产、运输、洗涤、侵蚀、废弃的过程中,不可避免地会被释放到自然环境中。在复杂环境因素影响下,纳米银本身的赋存状态发生转化,并对生态环境构成严重威胁。因此,探究纳米银在环境中的迁移转化过程及其对生态环境的潜在风险成为相关领域的研究热点。针对纳米银研究现状中存在的不足,综述了天然有机质、pH值、溶解氧、离子强度、光照等环境因素对纳米银迁移转化行为以及其对微生物毒性效应的影响,并进一步深入探讨了纳米银的毒理机制,旨在为纳米银的环境行为特征研究以及风险评估提供理论基础。     

微塑料与有毒污染物相互作用及联合毒性作用研究进展

随着塑料产品的广泛应用,微塑料(microplastics,MPs)污染已经成为全球关注的重大环境问题.海洋中的MPs能够与有毒污染物(如有机污染物、重金属和纳米颗粒等)发生相互作用,对海洋生物产生复合效应.因此,MPs与环境中有毒污染物的联合毒性效应越来越引起人们的关注.本文首先概括总结出MPs对海洋生物的毒性效应及致毒机制,包括遮蔽效应、氧化应激、免疫毒性、生殖毒性、遗传毒性、神经毒性和行为毒性等方面:随后分别讨论了MPs和有机污染物、重金属以及人工纳米颗粒的联合毒性效应,从微塑料对污染物的吸附、富集和载体效应着手分析微塑料与污染物之间的相互作用,凝练得出MPs增强或抑制污染物毒性的作用机制,包括微塑料改变污染物的生物可利用性、微塑料改变生物体对污染物的胁迫响应、微塑料与污染物发生交互作用等;最后对微塑料与有毒污染物联合毒作用研究的发展方向进行了展望,建议在未来研究中重点关注环境特征的次生微塑料与有毒污染物相互作用的环境行为和生物效应,特别是通过食物链的传递作用.以期为准确评估和深入理解微塑料的海洋环境和人类健康风险提供理论依据.     

纳米银与银离子对土壤微生物及酶活性的影响

为研究纳米银和银离子对土壤微生物的影响,采用土壤培养方式,对不同剂量纳米银(10、50、100 mg·kg~(-1))和银离子(1、5、10 mg·kg~(-1))暴露下黄褐土、砖红壤中可培养微生物数量及土壤酶活性(脲酶、荧光素二乙酸酯水解酶、蔗糖酶、过氧化氢酶)进行研究,并采用纯培养方法对纳米银和银离子暴露下的大肠杆菌(Escherichia coli)、金黄色葡萄球菌(Staphylococcus aureus)凋亡情况进行检测,对纳米银释放的银离子毒性进行评估。结果表明,随着纳米银剂量的增加,土壤可培养微生物数量显著减少,脲酶和过氧化氢酶活性降低,蔗糖酶、荧光素二乙酸酯水解酶(FDA酶)活性没有显著变化;银离子处理中微生物数量明显减少,但土壤酶活性被激活。10 mg·L~(-1)纳米银暴露1 h后大肠杆菌、金黄色葡萄球菌凋亡率、死亡率增高;随着培养时间的延长,纳米银缓慢释放银离子,并促进大肠杆菌的凋亡。综上分析,纳米银能够抑制土壤可培养微生物生长和酶活性,其中脲酶、过氧化氢酶对纳米银较为敏感,蔗糖酶、FDA酶受纳米银的影响较小;纳米银的毒性一方面是其本身的特异抗菌性,也有部分来自缓慢释放的银离子。     

Verhalten von Nanosilber in Kläranlagen und dessen Einfluss auf die Nitrifikationsleistung in Belebtschlamm

Background, aim and scope The application of nanosilver is increasing. Knowledge on the fate and behavior of nanosilver in wastewater and wastewater treatment plants is scarce. Studies under real world conditions are completely lacking. We studied (1) the impact of nanosilver on the nitrification of sewage sludge, (2) quantified the mass flow of nanosilver in a pilot-plant, and (3) verified the mass balance in a full-scale municipal wastewater treatment plant where nanosilver is introduced to the municipal plant by an indirect discharger. Materials and Methods The addition of four different nanosilver additives on ammonia oxidation in activated sludge has been studied in batch-reactors at two concentrations (1, 100?mg/L Ag) with two exposure times (2?h, 6?days). The pilot-plant treating 70 population equivalents of domestic wastewater is operated with a 12?day sludge age. Nanosilver was applied to the activated sludge tank within two sludge ages. The silver concentrations were measured in sludge and effluent samples during dosing and the following two sludge ages. The adsorption and speciation of silver particles has been analyzed using scanning electron microscopy (SEM) coupled with energy dispersive X-ray spectroscopy (EDX). Influent, effluent and sludge were sampled on a full-scale plant (60?000 equivalent inhabitants) and analyzed for silver. Results Silver nitrate, metallic nanosilver, nano-scaled silver chloride and microcomposite silver did not show any effect on ammonia oxidation after the addition of 1?mg/L Ag to the activated sludge (corresponding to 250?mg Ag per kg solids). In contrast, 100?mg/L Ag inhibited the nitrification process by 100?% after the addition of silver nitrate and 20–30?% after addition of colloidal polymer-coated nanosilver. A complete mass balance of the pilot-plant, a steady-state system with known fluxes, demonstrates significant enrichment of silver in the sewage sludge (96?%) after the addition of silver chloride to the plant and small losses of silver into the secondary effluent (4?%). The mass fluxes are similar to metallic colloidal nanosilver investigated under the same conditions. The mass balance has been consistently confirmed by the full-scale study in a municipal wastewater treatment plant. The silver fluxes correspond to the fluxes of the suspended solids in sludge and effluent. Overall, it is estimated that from public wastewater treatment plants about 4–40?mg/a Ag per inhabitant equivalent are discharged annually to the receiving water. The analysis by SEM-EDX demonstrates adsorption and incorporation of nanosilver on biological flocs. This method yields first insight into complex building and transformation of silver associated with sulfide after adding metallic nanosilver and silver chloride to wastewater. Discussion Silver ions released from nanosilver react immediately with large amounts of chloride present in wastewater to form silver chloride. Silver ions may react with organic ligands or sulfide groups additionally. Consequently, even silver nitrate added with 1?mg/L Ag (250?mg Ag/kg TS) to activated sludge did not inhibit nitrification activity. Very high amounts of nanosilver, i.?e. 100?mg/L Ag, overburdened the system and equilibrium condition between silver ion release and ligands was not reached. The mass balance reflects the excellent attachment of nanosilver to activated sludge and biological flocs. Therefore, the main elimination process of nanosilver is attachment to the activated sludge. The elimination of nanosilver is high compared to organic and inorganic micro pollutants omnipresent in wastewater. Any further reduction of suspended solids in the effluent water will reduce the silver load. Conclusions Generally, in wastewater nanosilver occurs bonded to activated sludge flocs and therefore the elimination of nanosilver is efficient under operation conditions typical for wastewater treatment plants. The major fraction of nanosilver is removed from the system by the excess sludge withdrawal. Nonetheless, the efficiency may be further improved by a tertiary filtration step. All analyses of influent, effluent and sludge confirmed that silver exists as silver sulfide. Due to a negligible water solubility of this silver species, silver ions are not subsequently released. Recommendations and perspectives Nanosilver research should be driven to the identification of transformation processes in real environmental matrices and the influence of coatings on the adsorption behavior. There is no need for action to take special measures for nanosilver removal in the area of municipal wastewater treatment plants compared to ubiquitous hazardous organic pollutants may present in wastewater. Nevertheless, source control measures following the precautionary principle should be performed.     

Enhanced antimicrobial activity of the food-protecting nisin peptide by bioconjugation with silver nanoparticles

Nisin is an antimicrobial peptide widely used in the food industry. The efficacy of nisin has decreased due to the development of resistant bacteria. For instance, bacteria such as Staphylococcus aureus have resistance by digesting nisin using the nisinase enzyme. The efficacy of nisin could be improved using bioconjugation with metal nanoparticles. Here we synthesized silver nanoparticles using the extract of Cymbopogon citratus; then, we bioconjugated those silver nanoparticles with nisin to form a nanosilver bioconjugate. Silver nanoparticles and silver bioconjugate were characterized by UV–Vis spectroscopy, nanoparticle tracking analysis, zeta potential measurement and transmission electron microscopy. In vitro antimicrobial efficacy of both silver nanoparticles and silver bioconjugate was evaluated against selected food spoilage microorganisms such as Listeria monocytogenes, S. aureus, Pseudomonas fluorescens, Aspergillus niger and Fusarium moniliforme. Results show that the antimicrobial potential of nisin increased after bioconjugation with silver nanoparticles. Further, we developed agar film containing nanosilver bioconjugate and also evaluated its antimicrobial activity against selected food spoilage microorganisms. The agar film demonstrated maximum activity against P. fluorescens, of 19 mm, and the minimum against F. moniliforme, of 12 mm. Overall, agar film containing nisin and silver nanoparticles can be used against food spoilage microorganisms.     

Effect of Zinc Oxide nanoparticles on cellular oxidative stress and antioxidant defense mechanisms in mouse liver

Zinc oxide nanoparticles (ZnO₂), a common ingredient of cosmetics has a huge variety of applications. Previous studies reported oxidative stress mediated toxicity of ZnO₂ nanoparticles on various mammalian cell lines. Although zinc (Zn) is an essential mineral at higher concentrations this metal is toxic. The present study focused on size determination by monitoring changes in activities of antioxidant defense mechanism in response to oxidative stress induced by ZnO₂ nanoparticles using mouse liver tissue homogenates. The study also investigated effects of oxidative stress induced DNA damage by determining formation of 8-OHdG in mouse liver homogenate. A cytotoxicity assay was also carried out in L929 cells to determine cell viability. The results of the study indicated that 50μg/ml of ZnO₂ nanoparticles induced 50% cell death. Alterations in antioxidant parameters and 8-OHdG were also noted. Data showed that there was a concentration-dependent fall in cell viability, decrease antioxidant enzyme levels and increase formation of DNA adduct (8-OHdG) when mouse liver tissue homogenate were exposed to ZnO₂ nanoparticles.     

纳米银对鱼类的毒性效应研究进展

纳米银作为一种新兴的纳米材料,由于其独特的抗菌性能而被广泛应用于各种商业化产品中。广泛的应用增加了它进入环境尤其是水环境的机率,从而对鱼类等水生生物产生潜在毒性效应。因此,近年来陆续开展了关于纳米银对鱼类的毒理学研究。本文根据国内外文献查阅及分析,综述了纳米银的制备、特性、应用、释放情况以及近几年来纳米银对鱼类的毒理学研究进展,对今后进一步开展相关研究工作提供参考。     

真菌毒素引起的氧化应激及其毒理学意义

真菌毒素是一类由真菌产生的次生代谢产物,由于其在自然界污染的普遍性和广泛的毒性作用,被给予了充分关注。从机理上入手来研究真菌毒素毒性作用的起因具有重要意义。真菌毒素根据结构分类可达400种之多,它们的机理也各有不同,但是越来越多的研究表明真菌毒素与氧化应激有重大关联。真菌毒素引起的氧化应激能引起细胞毒性作用,还参与了其他靶点的毒性反应。同时真菌毒素能干扰细胞抗氧化系统的功能,降低细胞对毒素的抵抗能力。本文主要综述了真菌毒素中与氧化应激有密切联系的几种毒素的毒性作用,重点阐述了其与氧化应激之间的关系,以期对真菌毒素的毒性机理有更进一步的认识。     

ZnO纳米粒子通过线粒体通路抑制小鼠光感受器细胞Na~+/K~+-ATP酶表达和活性的作用研究

氧化锌(ZnO)纳米粒子已被发现具有生物毒性,氧化应激被认为是最重要的因素之一。前期实验证实,ZnO纳米粒子能显著减少锰超氧化物歧化酶(Mn SOD)蛋白的表达,降低Mn SOD活性。本文通过检测乳酸脱氢酶(LDH)释放、线粒体活性氧(ROS)水平和膜电位(Δφm)、延迟整流钾电流变化和Na~+/K~+-ATP酶的表达及活性等变化,检测ZnO纳米粒子对小鼠光感受器细胞的细胞毒作用。结果表明,ZnO纳米粒子可显著增强小鼠光感受器细胞中LDH的释放、增加线粒体内ROS水平并下调Δφm、阻断延迟整流钾电流,同时降低Na~+/K~+-ATP酶的表达及活性,从而对小鼠视网膜光感受器细胞产生细胞毒作用,提示ZnO纳米粒子可通过线粒体通路引起氧化应激,从而抑制小鼠光感受器细胞Na~+/K~+-ATP酶表达和活性,产生细胞毒性,导致细胞死亡。本文的研究结果有助于理解ZnO纳米粒子引起细胞毒性的作用机理。     

微囊藻毒素诱导细胞氧化胁迫的研究进展(Progress in Oxidative Stress on Cell Induced by Microcystin)

微囊藻毒素对生物机体具有强烈的毒性.近几年的研究表明,微囊藻毒素能够诱导细胞产生氧化胁迫,这可能是微囊藻毒素的致毒机理的一个重要方面.在总结国内外相关研究基础上,论文从微囊藻毒素诱导细胞氧化损伤以及影响其抗氧化防御系统两个方面综述了微囊藻毒素诱导细胞氧化应激的研究进展.