Determination of nephrotoxicity and genotoxic potential of silver nanoparticles in Swiss albino mice

Silver nanoparticles (AgNPs) possess properties that are important for industrial and medical applications. This study is aimed to investigate intra-peritoneal toxicity of AgNPs at 26, 52 or 78 mg/kg/day for 5 days in mice Swiss albino mice. The effects on oxidative stress markers activities of serum superoxide dismutase (SOD) and catalase (CAT), levels of serum glutathione (GSH), apoptosis (TUNEL assay), DNA strand breaks (comet assay) in lymphocytes, as well as histopathological of kidney tissue were determined. AgNPs significantly increased SOD and CAT activities reduced GSH levels. In kidney apoptosis (TUNEL assay) while DNA strand breaks (comet assay) in lymphocytes revealed that AgNPs at concentration 78 mg/kg produced significant apoptosis and DNA damage. AgNPs also produced associated histological renal tissue damage. Evidence suggests that AgNPs-mediated alterations may be attributed to oxidative stress.     

Involvement of mitochondrial dysfunction in nanosized lead oxide induced cellular damage in human lung alveolar epithelial cells

High levels of industrial lead (Pb) exposure have decreased in the last 10 years as an outcome of removal of the metal from gasoline and paints. However, environmental Pb exposures remain extensive and may be correlated with adverse human health outcomes. The present study was designed to examine molecular mechanisms underlying cytotoxicity of lead oxide nanoparticles (PbONPs) on human lung alveolar epithelial (A549) cells. When A549 cells were incubated with PbONPs, the production of reactive oxygen species was enhanced as observed by 2',7'-dichlorodihydrofluorescein diacetate. PbONPs significantly reduced proliferation of A549 cells and increased caspase3 activity. In addition, exposure of PbONPs decreased levels of glutathione, and increased lipid peroxide levels and activities of superoxide dismutase and catalase. Exposure of PbONPs enhanced DNA damage as evidenced by tail DNA (%) and olive tail moment. Taken together, these finding indicated that PbONPs diminished cell proliferation and increased apoptotic cell death of A549 cells.     

氧化胁迫参与硫酸锌诱导的酵母细胞死亡

以模式生物酵母为材料,研究了不同浓度硫酸锌对酵母细胞的致死效应,以及活性氧(ROS)在硫酸锌诱导酵母凋亡中的作用.结果显示,低浓度处理组中,酵母细胞的相对生长率、超氧化物歧化酶活性和总抗氧化能力升高,超氧化物歧化酶相关基因SOD1和SOD2表达增强,而细胞存活率和MDA含量无明显变化.高浓度(3和5 mmol·L~(-1))处理组中,野生株酵母超氧化物歧化酶活性和总抗氧化能力明显下降,SOD1和SOD2基因表达受到明显抑制,胞内ROS水平和MDA含量升高,细胞死亡率显著上升;在相同锌处理组中,突变体ΔSOD1对硫酸锌的耐受性明显差于野生株BY4741,ΔSOD1胞内ROS水平和细胞凋亡率显著高于野生株,而ΔSOD2与野生株间无显著差异.结果表明,低浓度硫酸锌可促进酵母细胞生长,可能诱导了酵母细胞生长的Hormesis效应;高浓度硫酸锌可引起酵母细胞氧化损伤,而锌胁迫诱导的胞内ROS水平升高是酵母细胞死亡的一个诱因.该研究结果可为锌化物的毒性作用及其健康风险评估提供理论依据.     

Fluoride induces DNA damage and cytotoxicity in human hepatocellular carcinoma cells

Humans are primarily exposed to fluoride (Fl), a widespread environmental pollutant, via contaminated drinking water and foodstuffs. The aim of this study was to examine whether sodium fluoride (NaF) exerted cytotoxic effects in human hepatocarcinoma (HepG2) cells. HepG2 cells were incubated with different concentrations of NaF and reactive oxygen species (ROS) levels, cell cycle, apoptosis, and DNA damage determined. Concentration-dependent studies showed that exposure to HepG2 cells with different concentrations of NaF for 24 hr significantly decreased cell viability and intracellular antioxidant capacity. Furthermore, NaF exposure increased lipid peroxidation levels and accumulation of intracellular ROS; and lowered antioxidant glutathione concentrations. In addition to oxidative impairments, NaF treatment enhanced HepG2 cell death via apoptotic pathway as evidenced by DNA fragmentation and cell cycle arrest. Sodium fluoride treatment unregulated p53 level, and Bax and Bcl2 expression. Diminished cell viability and changes in cell cycle accompanied a rise in p53 expression.     

Immunotoxicity of atrazine in Balb/c mice

The present study was designed to investigate the immunotoxicity of atrazine (ATZ) in male Balb/c mice. ATZ (175, 87.5, and 43.75 mg/kg bw/day) was administered by gavage method for 28 days. The following indexes were determined in various groups of mice: body and organ weight; antibody aggregation of serum hemolysin; proliferative response of splenocytes to ConA; delayed-type hypersensitivity (DTH); natural killer cell activity; clearance of neutral red and nitric oxide (NO) release from peritoneal macrophages; apostosis and necrosis of splenocytes and thymocytes; cytokine production; and serum lysozyme. Results showed that cell-mediated, humoral immunity, and non-specific immune function in the high-dose ATZ group were suppressed; NO release and interferon-γ(IFN-γ)/interleukin-4 (IL-4) were also significantly decreased in the high-dose group. In the medium-dose group, the proliferation response and IFN-γ production was significantly decreased. In the low-dose group, the proliferation response was significantly decreased. Serum lysozyme was decreased in the ATZ-treated groups. The percentage of early apoptosis in thymocytes was increased significantly in high- and medium-dose ATZ groups. In conclusion, ATZ elicited an inhibitory effect on cell-mediated immunity, humoral immunity, and non-specific immune function of mice.     

Genotoxicity in the freshwater gastropod Lymnaea luteola L: assessment of cell type sensitivities to lead nitrate

The aquatic ecosystems are converting into the highly contaminated site due to environmental pollutants. The present study explores the oxidative stress and toxic potential of lead nitrate in freshwater snail Lymnaea luteola (L. luteola) L. The snails were exposed to an environmentally relevant concentration of lead nitrate for 24 and 96?h. Later exposure to lead nitrate (0, 10, 20 and 40?µg/mL) to the freshwater snail, the level of reactive oxygen species, malondialdehyde and nitric oxide (NO) were increased and glutathione, glutathione-S-transferase were decreased. Lead-nitrate-induced haemocyte cell death and it was observed by using Annexin-V FITC/PI through a flow cytometer. DNA damage in haemocyte cells was measured at above doses of lead-nitrate exposure for 24 and 96?h and it was compared to the untreated snail. Average tail DNA (%) and olive tail moment in single-cell gel test were increased dose and duration fashion and maximum DNA damage was measured at 96?h. These results indicate the potential toxicity and genotoxicity of lead nitrate in acute treatment to L. luteola and single-cell gel test are the assay for rapid detection of genetic effects.     

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。     

环境浓度下磺胺混合物对秀丽线虫(Caenorhabditis elegans)生长、饮食、抗氧化酶及其调控基因表达水平的影响

磺胺类药物在环境中的普遍残留引起了人们对其潜在效应的担忧。因为磺胺混合物的效应不能通过单个物质效应进行准确预测,所以需要针对混合物效应开展深入研究。将秀丽线虫暴露于4种常用磺胺药物(磺胺嘧啶、磺胺吡啶、磺胺甲噁唑和磺胺甲嘧啶)组成的、环境浓度水平(0.01 mg·L-1)的混合物后,对生长调控基因dbl-1和egl-4,饮食调控基因eat-2和eat-18,过氧化氢酶(CAT)编码基因ctl-2和ctl-3,寿命调控基因sir-2,以及凋亡调控基因ced-4的表达水平进行检测。暴露组与空白对照组的结果比较表明,秀丽线虫dbl-1表达水平没有显著变化(下调3%),egl-4表达下调18%,解释了生长的抑制效应(抑制率为15.6%)。eat-2和eat-18的表达水平下调幅度相似,介于20%~22%之间,该幅度高于饮食的抑制效应(10.7%)。ctl-2和ctl-3的表达水平上调,分别比空白对照组高101%与66%,该幅度显著小于0.01 mg·L-1磺胺混合物暴露对CAT活性的刺激效应(比空白对照组高789.5%)。此外,sir-2的表达水平没有显著变化,与线虫寿命没有受到显著影响相一致。同时,ced-4表达上调32%,预示凋亡水平的显著增加。egl-4、eat-2、ctl-2和ced-4基因表达水平的显著变化分别表明磺胺混合物对β转化生长因子(TGF-β),烟酰乙酰胆碱受体(n AChR)、抗氧化系统以及细胞凋亡等多个方面的产生影响。     

铁矿区水环境样品对秀丽隐杆线虫的毒性研究

矿区环境问题是近年来各研究领域关注的焦点。为探究矿区水环境潜在的生物安全性问题,以安徽省霍邱县大型铁矿区地表水体为研究对象,以秀丽隐杆线虫作为实验动物模型,并以其生长和生殖发育作为生物检测终点,考察了线虫对该矿区周边5个地表水样品的毒性效应的响应。结果表明,矿区水环境样品对线虫的生长和生殖发育具有明显的损伤效应,且这种损伤效应的大小与水样采集点距离采矿区的远近以及水样中主要污染物的含量密切相关。进一步通过主成分分析发现,总铁、可溶性铁、铜、铬和砷是环境水样造成线虫毒性效应的主要影响因子。上述研究结果为铁矿区水环境生物安全性的监测和评价提供了一种新的技术方法和新的视角,并为铁矿区健康风险规避提供新的思路和理论基础数据。     

Cadmium sulfide nanoparticle induces oxidative stress and pro-inflammatory effects in human lung adenocarcinoma epithelial cells

Cadmium sulfide nanoparticles (CdSNP) are increasingly used in biological applications. This study was undertaken to understand the mechanisms underlying adverse effects of CdSNP using human lung adenocarcinoma epithelial (A549) cells. Cellular toxicity was evaluated by using 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide and neutral red assays. Results showed that CdSNP reduced mitochondrial function and induced lysosomal activity in concentration and time-dependent manner. CdSNP produced oxidative stress as evidenced by reduction of glutathione (GSH) levels and increase in reactive oxygen species and lipid peroxidation levels. Induction of caspase-3 enzymes and condensed, fragmented nuclei was observed in CdSNP-treated cells. Furthermore, the levels of interleukin-8, tumor growth factor and DNA fragmentation were significantly higher in CdSNP exposed cells. Data indicated that toxicity of CdSNP noted in A549 cells may be mediated through oxidative stress. This study warrants more comprehensive assessment of CdSNP prior to industrial applications.