Coating independent cytotoxicity of citrate- and PEG-coated silver nanoparticles on a human hepatoma cell line

The antibacterial potential of silver nanoparticles(AgNPs) resulted in their increasing incorporation into consumer,industrial and biomedical products.Therefore,human and environmental exposure to AgNPs(either as an engineered product or a contaminant)supports the emergent research on the features conferring them different toxicity profiles.In this study,30 ran AgNPs coated with citrate or poly(ethylene glycol)(PEG) were used to assess the influence of coating on the effects produced on a human hepatoma cell line(HepG2),namely in terms of viability,apoptosis,apoptotic related genes,cell cycle and cyclins gene expression.Both types of coated AgNPs decreased cell proliferation and viability with a similar toxicity profile.At the concentrations used(11 and 5 μg/mL corresponding to IC50 and-IC10 levels,respectively) the amount of cells undergoing apoptosis was not significant and the apoptotic related genes BCL2(anti-apoptotic gene)and BAX(pro-apoptotic gene) were both downregulated.Moreover,both AgNPs affected HepG2 cell cycle progression at the higher concentration(11 μg/mL) by increasing the percentage of cells in S(synthesis phase) and G2(Gap 2 phase) phases.Considering the cell-cycle related genes,the expression of cyclin B1 and cyclin E1 genes were decreased.Thus,this work has shown that citrate- and PEG-coated AgNPs impact on HepG2 apoptotic gene expression,cell cycle dynamics and cyclin regulation in a similar way.More research is needed to determine the properties that confer AgNPs at lower toxicity,since their use has proved helpful in several industrial and biomedical contexts.     

In vitro cytotoxicity assessment of roundup (glyphosate) in L-02 hepatocytes

The goal of the present study was to elucidate the in vitro cytotoxicity of Roundup and to reveal the possible related mechanisms in L-02 hepatocytes. By detecting reactive oxygen species (ROS) production, glutathione (GSH)/superoxide dismutase (SOD) levels, mitochondrial permeability transition pore (PTP) open rate, apoptosis-inducing factor (AIF) release, intracellular Ca²⁺ concentration, and alanine aminotransferease (ALT)/aspartate aminotransferase (AST) leakage, we determined that Roundup induced anti-oxidant system inhibition, mitochondria damage, DNA damage, membrane integrity and permeability changes, and apoptosis in L-02 hepatocytes. By revealing the mechanistic insights of Roundup-induced cytotoxicity, our results are valuable for the design of preventive and therapeutic strategies for the occupational population exposed to Roundup and other pesticides.     

ZnO nanoparticles induced cytotoxicity on human pulmonary adenocarcinoma cell line LTEP-a-2

Novel nanoparticles (NPs) such as zinc oxide (ZnO) NPs are widely produced and applied in our daily lives at a rapid pace. Thus, the toxicity of ZnO NPs should be monitored as an important standard for environmental risk assessment. Here we assessed the in vitro cytotoxicity of ZnO NPs on human pulmonary adenocarcinoma cells LTEP-a-2 by tetrazolium salt colorimetric assay of cell proliferation in the presence or absence of ZnO NPs. ZnO NPs-induced morphological changes in LTEP-a-2 cells were examined by light and scanning electron microscopy. The mechanism by which ZnO NPs impose the cytotoxic effect was investigated by a combination of active oxygen test, lactose dehydrogenase-release assay, and apoptosis detection. Results showed that ZnO NPs significantly inhibited the proliferation and induced evident morphological changes (cell shrinkage and chromosome condensation) in LTEP-a-2 cells. Additionally, ZnO NPs increased the level of intracellular reactive oxygen species and induced the formation of apoptotic vesicles as well as the lysis of cell nuclei. Zn²⁺ ions released from ZnO NPs into aqueous solution are important components that exert cytotoxic effects on LTEP-a-2 cells. This study provides new insights to the cytotoxicity of ZnO NPs against human health.     

Evaluation of the cytotoxic effects of glyphosate herbicides in human liver,lung, and nerve

Glyphosate-based herbicides are broad-spectrum pesticides widely used in the world, which is considered a highly safe pesticide due to their target specificity, but recently, there has been an ongoing controversy regarding their carcinogenicity and possible side effects of glyphosate on human health. Commercial glyphosate-based herbicides (GBHs) consist of declared active ingredient (glyphosate salts) and a number of formulants such as ethoxylated formulants (4130®, 3780^®, and A-178^®). The aim of our study is to investigate whether the toxicity of GBHs is related to formulants. The effects of GBHs on human health were studied at the cellular level based on their toxicity to liver, lungs and nerve tissue. The inhibitory toxicity to cell viability by GBHs was examined with cell-based systems using three human cell lines: HepG2, A549, and SH-SY5Y. Data obtained showed that all tested ethoxylated formulants and their mixtures with declared active ingredient glyphosate isopropylamine salt (GP) have significant inhibitory effect on cell proliferation, while the declared active ingredient has no significant toxicity. Our study demonstrates that the toxic effect of GBH is primarily due to the use of formulants. This result suggests that GP is relatively safe and a new approach for the assessment of toxicity should be made.     

转Bar基因稻谷全蛋白对体外培养小鼠淋巴细胞的毒性

为了评价转基因大米Bar68-1全蛋白的急性细胞毒性,分别以25、50、100和200μg·mL-1转基因大米Bar68-1全蛋白孵育昆明小鼠淋巴细胞,并各孵育2 h、6 h、24 h,然后通过体外试验用CCK-8及中性红摄取试验检测细胞毒性大小。在经过不同的孵育时间段后,阳性对照组淋巴细胞的细胞存活率与空白对照组相比,存在显著差异(p0.05)。其中,CCK-8试验、中性红试验测得细胞存活率存在着明显的损伤作用-时间效应关系。转基因大米Bar68-1全蛋白组孵育的淋巴细胞存活率与非转基因大米D68全蛋白组孵育的淋巴细胞相比无明显差异(p0.05),且与空白对照组细胞存活率差异不显著(p0.05)。结果显示,转基因大米Bar68-1全蛋白与非转基因大米D68全蛋白急性细胞毒性效应相似,对小鼠淋巴细胞无明显急性毒性。     

Cytotoxicity and autophagy induction by graphene quantum dots with different functional groups

Graphene quantum dots(GQDs) possess great potential in various applications due to their superior physicochemical properties and wide array of available surface modifications.However, the toxicity of GQDs has not been systematically assessed, thus hindered their further development; especially, the risk of surface modifications of GQDs is largely unknown. In this study, we employed a lung carcinoma A549 cells as the model to investigate the cytotoxicity and autophagy induction of three types GQDs, including cGQDs(COOH-GQDs), hGQDs(OH-GQDs), and aGQDs(NH_2-GQDs). The results showed hGQDs was the most toxic, as significant cell death was induced at the concentration of 100 μg/mL,determining by WST-1 assay as well as Annexin-V-FITC/PI apoptosis analysis, whereas cGQDs and aGQDs were non-cytotoxic within the measured concentration. Autophagy detection was performed by TEM examination, LC3 fluorescence tracking, and Westernblot. Both aGQDs and hGQDs induced cellular autophagy to various degrees except for cGQDs. Further analysis on autophagy pathways indicated all GQDs significantly activated p-p38 MAPK; p-ERK1/2 was inhibited by aGQDs and hGQDs but activated by c GQDs. p-JNK was inhibited by aGQDs and c GQDs, while activated by hGQDs. Simultaneously, Akt was activated by hGQDs but inhibited by aGQDs. Inhibition of autophagy by 3-MA significantly increased the cytotoxicity of GQDs, suggesting that autophagy played a protective role against the toxicity of GQDs. In conclusion, c GQDs showed excellent biocompatibility and may be considered for biological applications. Autophagy induction may be included in the health risk assessment of GQDs as it reflects the stress status which may eventually lead to diseases.     

Chemical composition of the mycelium of Daldinia eschscholtzii北大核心CSCD

To investigate the chemical composition of the fungus Daldinia eschscholtzii, the compounds were separated by silica gel, Sephadex LH-20, and preparative chromatography. Their structures were identified by spectral methods. The MTT method was applied to measure the cytotoxicity of representative components. Eleven compounds were isolated and identified as 3β-hydroxyl-6,22-dien-5α,8α-peroxynitrite (1); ergosterol-9(11)-dehydroperoxide (2); mangiferonic acid (3); ergosta-4,6,8 (14),22-tetraen-3-one (4); (+)-syringaresinol (5); 3,5,3',5'-tetramethoxy-4,4,-diphenol (6); 5-methoxycoumarin (7); 5-hydroxy-2-methyl-4H-chromen-4-one (8); (2R,4R)-3,4-dihydro-5-methoxy-2-methyl-2H-1-benzopyran-4-ol (9); 2,3-dihydro-5-methoxy-2-methylchromen-4-one (10); and 7β-caruilignan C (11), respectively. Compound 4 showed inhibitory activity against H1299, H460, HGC-27, A5491, and MNK-45, with the IC50 value of 25.2 ± 2.9, 32.3 ± 4.2, 29.2 ± 1.2, 33.9 ± 3.7, and 18.0 ± 7.0 μmol/L, respectively. © 2018 Science Press. All rights reserved.     

Cytotoxicity estimation of ionic liquids based on their effective structural features

Cytotoxicity of a diverse set of 227 ionic liquids (taken from UFT/Merck Ionic Liquids Biological Effects Database) containing 94 imidazolium, 53 pyridinium, 23 pyrrolidinium, 22 ammonium, 15 piperidinium, 10 morpholinium, 5 phosphanium, and 5 quinolinium cations in combination with 25 different types of anions to Leukemia Rat Cell Line (IPC-81) was estimated from their structural parameters using quantitative structure - toxicity relationship “QSTR” methodology. Linear and nonlinear models were developed using genetic algorithm (GA), multiple linear regressions (MLR) and multilayer perceptron neural network (MLP NN) approaches. Robustness and reliability of the constructed models were evaluated through internal and external validation methods. Furthermore, chemical applicability domain was determined via leverage approach. In this work, it was revealed that the cationic moieties make the major contribution to cytotoxicity and the anionic parts play a secondary role in cytotoxicity of the ionic liquids studied here. Structural information represented in this work, can be used for a rational design of safer ILs.     

Synergistic increase in cell lethality by dieldrin and H2O2 in rat thymocytes: Effect of dieldrin on the cells exposed to oxidative stress

Dieldrin, one of persistent pesticides, is highly resistant to biotic and abiotic degradation. It is accumulated in organisms. Recent studies suggest that dieldrin exerts a potent cytotoxic action on cells exposed to oxidative stress. In this study, the effect of dieldrin on rat thymocytes exposed to hydrogen peroxide (H₂O₂)-induced oxidative stress was examined. Dieldrin at 5 μM and H₂O₂ at 300 μM slightly increased cell lethality from a control value of 5.4 ± 0.5% (mean ± standard deviation of four experiments) to 7.8 ± 1.3% and 9.0 ± 0.3%, respectively. Simultaneous application of dieldrin and H₂O₂ significantly increased cell lethality to 46.2 ± 1.8%. The synergistic increase in cell lethality was dependent on dieldrin concentration (0.3–5 μM) but not on H₂O₂ concentration (30–300 μM). Dieldrin accelerated H₂O₂-induced cell death, which was estimated with the help of annexin V-FITC and propidium iodide. Presence of either dieldrin or H₂O₂ decreased the cellular content of nonprotein thiol and increased intracellular Zn²⁺ concentration. The combination of dieldrin and H₂O₂ further pronounced these effects. TPEN, a chelator of intracellular Zn²⁺, significantly attenuated the synergistic increase in cell lethality induced by dieldrin and H₂O₂. It is, therefore, suggested that dieldrin augments the cytotoxicity of H₂O₂ in a Zn²⁺-dependent manner.