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Assessment of lung cell toxicity of various gasoline engine exhausts using a versatile in vitro exposure system
2018
Bisig, Christoph | Comte, Pierre | Güdel, Martin | Czerwiński, Janusz | Mayer, Andreas | Müller, Loretta | Petri-Fink, Alke | Rothen-Rutishauser, Barbara
Adverse effect studies of gasoline exhaust are scarce, even though gasoline direct injection (GDI) vehicles can emit a high number of particles.The aim of this study was to conduct an in vitro hazard assessment of different GDI exhausts using two different cell culture models mimicking the human airway. In addition to gasoline particle filters (GPF), the effects of two lubrication oils with low and high ash content were assessed, since it is known that oils are important contributors to exhaust emissions.Complete exhausts from two gasoline driven cars (GDI1 and GDI2) were applied for 6 h (acute exposure) to a multi-cellular human lung model (16HBE14o-cell line, macrophages, and dendritic cells) and a primary human airway model (MucilAir™). GDI1 vehicle was driven unfiltered and filtered with an uncoated and a coated GPF. GDI2 vehicle was driven under four settings with different fuels: normal unleaded gasoline, 2% high and low ash oil in gasoline, and 2% high ash oil in gasoline with a GPF. GDI1 unfiltered was also used for a repeated exposure (3 times 6 h) to assess possible adverse effects.After 6 h exposure, no genes or proteins for oxidative stress or pro-inflammation were upregulated compared to the filtered air control in both cell systems, neither in GDI1 with GPFs nor in GDI2 with the different fuels. However, the repeated exposure led to a significant increase in HMOX1 and TNFa gene expression in the multi-cellular model, showing the responsiveness of the system towards gasoline engine exhaust upon prolonged exposure.The reduction of particles by GPFs is significant and no adverse effects were observed in vitro during a short-term exposure. On the other hand, more data comparing different lubrication oils and their possible adverse effects are needed. Future experiments also should, as shown here, focus on repeated exposures.
显示更多 [+] 显示较少 [-]ATM signals to AMPK to promote autophagy and positively regulate DNA damage in response to cadmium-induced ROS in mouse spermatocytes
2017
Li, Renyan | Luo, Xue | Zhu, Yijian | Zhao, Letian | Li, Lianbing | Peng, Qiang | Ma, Mingfu | Gao, Yanfei
Cadmium (Cd) is a toxic heavy metal and harmful to human health due to its ability to accumulate in organs. Previous studies have shown that Cd can induce DNA damage and autophagy. Autophagy can stabilize genetic material and DNA integrity. The aim of the present study was to determine the exact mechanism and role of autophagy induced by Cd in spermatozoa cells. Mouse spermatocyte-derived cells (GC-2) were treated with 20 μM Cd chloride for 24 h. The level of reactive oxygen species (ROS), DNA damage, autophagy and the expression of the molecular signaling pathway ATM/AMP-activated protein kinase (AMPK)/mTOR were determined. The results showed that Cd induced autophagy and DNA damage in GC-2 cells via ROS generation, and the autophagy signal pathway AMPK/mTOR was activated by ATM which is a DNA damage sensor. Melatonin, a well-known antioxidant, ameliorated DNA damage, and inhibited autophagy via the AMPK/mTOR signal pathway. Furthermore, after inhibition of autophagy by knockdown of AMPKα, increased DNA damage by Cd treatment was observed in GC-2 cells. These findings demonstrated the protective role of autophagy in DNA damage and suggested that the mechanism of autophagy induced by Cd was through the ATM/AMPK/mTOR signal pathway in spermatozoa cells.
显示更多 [+] 显示较少 [-]Reproductive toxicity of azoxystrobin to adult zebrafish (Danio rerio)
2016
Cao, Fangjie | Zhu, Lizhen | Li, Hui | Yu, Song | Wang, Chengju | Qiu, Lihong
In the past few decades, extensive application of azoxystrobin has led to great concern regarding its adverse effects on aquatic organisms. The objective of the present study was to evaluate the reproductive toxicity of azoxystrobin to zebrafish. After adult zebrafish of both sexes were exposed to 2, 20 and 200 μg/L azoxystrobin for 21 days, egg production, the fertilization rate, the gonadosomatic index (GSI) and hepatosomatic index (HSI), 17β-estradiol (E2), testosterone (T) and vitellogenin (Vtg) concentrations, and histological alterations in the gonads and livers were measured. Meanwhile, expression alterations of genes encoding gonadotropins and gonadotropin receptors (fshb, lhb, fshr and lhr), steroid hormone receptors (era, er2b and ar), steroidogenic enzymes (cyp11a, cyp11b, cyp17, cyp19a, cyp19b, hsd3b and hsd17b) in the hypothalamic-pituitary-gonad (HPG) axis and vitellogenin (vtg1 and vtg2) in the livers were also investigated. The results showed that reduced egg production and fertilization rates were observed at 200 μg/L azoxystrobin. In female zebrafish, reduced E2 and Vtg concentrations, decreased GSI, increased T concentrations, and histological alterations in the ovaries and livers were observed at 200 μg/L azoxystrobin, along with significant down-regulation of lhb, cyp19b, lhr, cyp19a, vtg1 and vtg2, and up-regulation of cyp17, hsd3b and hsd17b. In male zebrafish, increased E2 and Vtg concentrations, reduced T concentration and GSI, and histological alterations in the testes and livers were observed after exposure to 20 and 200 μg/L azoxystrobin, along with significant up-regulations of cyp19b, cyp11a, cyp17, cyp19a, hsd3b and hsd17b, vtg1 and vtg2. Moreover, cyp11a, hsd3b, cyp19a, vtg1 and vtg2 in male zebrafish were significantly up-regulated after treatment with 2 μg/L azoxystrobin. The results of the present study indicate that azoxystrobin led to reproductive toxicity in zebrafish and male zebrafish were more sensitive to azoxystrobin than female zebrafish.
显示更多 [+] 显示较少 [-]The potential toxicity of polystyrene nanoplastics to human trophoblasts in vitro
2022
Hu, Jianing | Zhu, Yueyue | Zhang, Jinwen | Xu, Yichi | Wu, Jiayi | Zeng, Weihong | Lin, Yi | Liu, Xiaorui
Nanoplastics (NPs), the emerging contaminants in recent years, widely distributed in the environment and are bioaccumulated and biomagnified in organisms through food chain. A growing number of studies have detected plastic particulates in human placenta and blood. However, few studies have focused on their effects during human pregnancy. Herein, human trophoblast HTR-8/Svneo cells were used to evaluate the effects and the possible mechanism of 100-nm polystyrene NPs on placental trophoblasts at the maternal-fetal interface. The results showed that NPs entered the trophoblastic cytoplasm, decreased cell viability, caused cell cycle arrest, reduced the cell migration and invasion abilities, increased level of intracellular reactive oxygen species and the production of proinflammatory cytokines (TNF-α and IFN-γ) in a dose-dependent manner. Furthermore, global transcriptome sequencing (RNA-Seq) was performed on HTR-8/Svneo cells with or without 100 μg/mL PS-NP exposure for 24 h. A total of 344 differentially expressed genes were detected. The gene functions for regulation of leukocyte differentiation, response to stimulus, cell cycle, apoptotic process, and cell adhesion were enriched. Thyroid hormone, Hippo, TGF-β and FoxO signaling pathways were activated. Collectively, our data provided evidences for the adverse consequences of NPs on the biological functions of trophoblasts, which provided new insights into the potential trophoblast toxicity of NPs in mammals.
显示更多 [+] 显示较少 [-]Grass carps co-exposed to environmentally relevant concentrations of cypermethrin and sulfamethoxazole bear immunodeficiency and are vulnerable to subsequent Aeromonas hydrophila infection
2020
Zhao, Hongjing | Wang, Yu | Guo, Menghao | Mu, Mengyao | Yu, Hongxian | Xing, Mingwei
The aquatic ecosystem is seriously damaged because of the heavy use of pesticides and antibiotics. Fish is the indispensable link between environmental pollution and human health. However, the toxic effects of environment-related concentrations of pesticides and antibiotics in fish have not been thoroughly studied. In this study, grass carps exposed to cypermethrin (CMN, 0.651 μg/L) or/and sulfamethoxazole (SMZ, 0.3 μg/L) for 42 days caused oxidative stress, apoptosis and immunodeficiency in the spleen of grass carps. CMN or/and SMZ exposure led to oxidative damage (consumption of antioxidant enzymes (superoxide dismutase and catalase)) and lipid peroxidation (accumulation of malondialdehyde), induced apoptosis (increases in TUNEL index, Bax/bcl-2, p53, puma and Caspase family expression). In addition, the levels of immunoglobulin M (IgM), complement 3 (C3) were significantly decreased in all treatment groups, which trend was also found in C-reactive protein in CMN and MIX group, and lysozyme in MIX group. Transcription of almost all genes involved in the Toll-like receptors (TLR) signaling pathway was up-regulated under CMN or/and SMZ exposure. However, when subsequently attacked by Aeromonas hydrophila for 2 days, the TLR pathway was inhibited in spleens of all treatment groups accompanied by higher mortality. Overall, the environmentally relevant concentration of CMN and SMZ damages the immune system, triggering oxidative stress and apoptosis in carps. And by affecting the conduction of TLR signaling pathway, CMN or/and SMZ exposure inhibits the innate immune response of fish and reducing their disease resistance. This study highlights the importance of rational and regulated use of these pesticides and antibiotics.
显示更多 [+] 显示较少 [-]A laboratory assessment of the potential effect of Cry1Ab/Cry2Aj-containing Bt maize pollen on Folsomia candida by toxicological and biochemical analyses
2017
The common soil arthropod Folsomia candida can survive well when fed only maize pollen and thus may be exposed to insecticidal proteins by ingesting insect-resistant genetically engineered maize pollen containing Bacillus thuringiensis (Bt) proteins when being released into the soil. Laboratory experiments were conducted to assess the potential effects of Cry1Ab/Cry2Aj-producing transgenic Bt maize (Shuangkang 12–5) pollen on F. candida fitness. Survival, development, and the reproduction were not significantly reduced when F. candida fed on Bt maize pollen rather than on non-Bt maize pollen, but these parameters were significantly reduced when F. candida fed on non-Bt maize pollen containing the protease inhibitor E-64 at 75 μg/g pollen. The intrinsic rate of increase (rm) was not significantly reduced when F. candida fed on Bt maize pollen but was significantly reduced when F. candida fed on non-Bt maize pollen containing E−64. The activities of antioxidant-related enzymes in F. candida were not significantly affected when F. candida fed on Bt maize pollen but were significantly increased when F. candida fed on non-Bt pollen containing E−64. The results demonstrate that consumption of Bt maize pollen containing Cry1Ab/Cry2Aj has no lethal or sublethal effects on F. candida.
显示更多 [+] 显示较少 [-]Pro-inflammatory effects and oxidative stress in lung macrophages and epithelial cells induced by ambient particulate matter
2013
Michael, S. | Montag, M. | Dott, W.
The objective of this study was to compare the toxicological effects of different source-related ambient PM10 samples in regard to their chemical composition. In this context we investigated airborne PM from different sites in Aachen, Germany. For the toxicological investigation human alveolar epithelial cells (A549) and murine macrophages (RAW264.7) were exposed from 0 to 96 h to increasing PM concentrations (0–100 μg/ml) followed by analyses of cell viability, pro-inflammatory and oxidative stress responses. The chemical analysis of these particles indicated the presence of 21 elements, water-soluble ions and PAHs. The toxicological investigations of the PM10 samples demonstrated a concentration- and time-dependent decrease in cell viability and an increase in pro-inflammatory and oxidative stress markers.
显示更多 [+] 显示较少 [-]Developmental exposure to chlorpyrifos causes neuroinflammation via necroptosis in mouse hippocampus and human microglial cell line
2022
Du, Ying | Yang, Yongyong | Wang, Yue | Wu, Nana | Tao, Junyan | Yang, Guanghong | You, Mingdan
Neurodevelopmental exposure to chlorpyrifos (CPF) could increase risks for neurological disorders, such as autism spectrum disorder, cognitive impairment, or attention deficit hyperactivity disorder. The potential involvement of microglia reactive to inflammatory stimuli in these neurological disorders has been generally reported. However, the concrete effects and potential mechanisms of microglia dysfunction triggered by developmental CPF exposure remain unclear. Therefore, we established mouse and human embryonic microglial cells (HMC3 cell) models of developmental CPF exposure to evaluate the effects of developmental CPF exposure on neuroinflammation and underlying mechanisms. The results showed that developmental exposure to CPF enhanced the expression of Iba1 in hippocampus. CPF treatment increased inflammatory cytokines levels and TSPO expression in hippocampus and HMC3 cells. The levels of necroptosis and necroptosis-related signaling RIPK/MLKL were increased in hippocampus and HMC3 cells following CPF exposure. Furthermore, the expression of TLR4/TRIF signaling was increased in hippocampus and HMC3 cells subjected to CPF exposure. Notably, the increased levels of TLR4/TRIF signaling, RIPK/MLKL signaling, necroptosis and pro-inflammatory cytokines induced by CPF treatment were remarkably inhibited by TAK-242 (a specific TLR4 inhibitor). Additionally, the necroptosis and pro-inflammatory cytokines production induced by CPF treatment were significantly relieved by Nec-1 (a specific RIPK1 inhibitor). In general, the above results suggested that activated microglia in hippocampus subjected to developmental CPF exposure underwent RIPK1/MLKL-mediated necroptosis regulated by TLR4/TRIF signaling.
显示更多 [+] 显示较少 [-]Heat stress during late gestation disrupts maternal microbial transmission with altered offspring’s gut microbial colonization and serum metabolites in a pig model
2020
He, Jianwen | Zheng, Weijiang | Tao, Chengyuan | Guo, Huiduo | Xue, Yongqiang | Zhao, Ruqian | Yao, Wen
Heat stress (HS) during gestation has been associated with negative outcomes, such as preterm birth or postnatal metabolic syndromes. The intestinal microbiota is a unique ecosystem playing an essential role in mediating the metabolism and health of mammals. Here we hypothesize late gestational HS alters maternal microbial transmission and structures offspring’s intestinal microbiota and serum metabolic profiles. Our results show maternal HS alters bacterial β-diversity and composition in sows and their piglets. In the maternal intestine, genera Ruminococcaceae UCG-005, [Eubacterium] coprostanoligenes group and Halomonas are higher by HS (q < 0.05), whereas the populations of Streptococcus, Bacteroidales RF16 group_norank and Roseburia are decreased (q < 0.05). In the maternal vagina, HS mainly elevates the proportions of phylum Bacteroidetes and Fusobacteria (q < 0.05), whereas reduces the population of Clostridiales Family XI (q < 0.05). In the neonatal intestine, maternal HS promotes the population of Proteobacteria but reduces the relative abundance of Firmicutes (q < 0.05). Moreover, the core Operational taxonomic units (OTU) analysis indicates the proportions of Clostridium sensu stricto 1, Romboutsia and Turicibacter are decreased by maternal HS in the intestinal and vaginal co-transmission, whereas that of phylum Proteobacteria and Epsilonbacteraeota, such as Escherichia-Shigella, Klebsiella, Acinetobacter, and Comamonas are increased in both the intestinal and vaginal co-transmission and the vagina. Additionally, Aeromonas is the only genus that is transmitted from environmental sources. Lastly, we evaluate the importance of neonatal differential OTU for the differential serum metabolites. The results indicate Acinetobacter significantly contributes to the differences in the adrenocorticotropic hormone (ACTH) and glucose levels due to HS (P < 0.05). Further, Stenotrophomonas is the most important variable for Cholesterol, low-density lipoprotein (LDL), diamine oxidase (DAO), blood urea nitrogen (BUN) and 5-hydroxytryptamine (5-HT) (P < 0.10). Overall, our data provides evidence for the maternal HS in establishing the neonatal microbiota via affecting maternal transmission, which in turn affects the maintenance of metabolic health.
显示更多 [+] 显示较少 [-]Development of ELISAs for the detection of vitellogenin in three marine fish from coastal areas of China
2018
Li, Yuejiao | Wang, Jun | Zheng, Mingyi | Zhang, Yabin | Ru, Shaoguo
Estrogenic pollution has aroused great concern for its adverse effects on marine organisms. This study aimed to establish biomarker-based methods for detecting environmental estrogens using vitellogenin (Vtg) of teleost fishes inhabiting coastal areas of China. Firstly, Vtgs in marbled flounder (Pseudopleuronectes yokohamae), black rockfish (Sebastes schlegelii) and fat greenling (Hexagrammos otakii) were purified, characterized and used to prepare antibodies. Then, Vtg ELISA for each species was developed using purified Vtg and its antibody. Marbled flounder Vtg ELISA had a working range of 3.9–500 ng/mL and a detection limit of 2.1 ng/mL, and black rockfish Vtg ELISA had strong cross-reactivity with marbled flounder Vtg. Furthermore, Vtg induction in male marbled flounder exposed to pentadecafluorooctanoic acid (PFOA) was measured by developed ELISA. Plasma Vtg concentrations were significantly increased with PFOA concentrations in seawater and fish muscle. Therefore, Vtg ELISAs for these species might be useful tools for monitoring marine environmental estrogens.
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