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Toxicogenomics provides insights to toxicity pathways of neonicotinoids to aquatic insect, Chironomus dilutus
2020
Wei, Fenghua | Wang, Dali | Li, Huizhen | Xia, Pu | Ran, Yong | Yau, Ching
Neonicotinoid insecticides have posed a great threat to non-target organisms, yet the mechanisms underlying their toxicity are not well characterized. Major modes of action (MoAs) of imidacloprid were analyzed in an aquatic insect Chironomus dilutus. Lethal and sublethal outcomes were assessed in the midges after 96-h exposure to imidacloprid. Global transcriptomic profiles were determined using de novo RNA-sequencing to more holistically identify toxicity pathways. Transcriptional 10% biological potency values derived from ranked KEGG pathways and GO terms were 0.02 (0.01–0.08) (mean (95% confidence interval) and 0.05 (0.04–0.06) μg L⁻¹, respectively, which were more sensitive than those from phenotypic traits (10% lethal concentration: 0.44 (0.23–0.79) μg L⁻¹; 10% burrowing behavior concentration: 0.30 (0.22–0.43) μg L⁻¹). Major MoAs of imidacloprid in aquatic species were identified as follows: the activation of nicotinic acetylcholine receptors (nAChRs) induced by imidacloprid impaired organisms’ nerve system through calcium ion homeostasis imbalance and mitochondrial dysfunction, which posed oxidative stress and DNA damage and eventually caused death of organisms. The current investigation highlighted that imidacloprid affected C. dilutus at environmentally relevant concentrations, and elucidated toxicity pathways derived from gene alteration to individual outcomes, calling for more attention to toxicity of neonicotinoids to aquatic organisms.
显示更多 [+] 显示较少 [-]Exposure to both formaldehyde and high relative humidity exacerbates allergic asthma by activating the TRPV4-p38 MAPK pathway in Balb/c mice
2020
Duan, Jiufei | Xie, Jing | Deng, Ting | Xie, Xiaoman | Liu, Hong | Li, Baizhan | Chen, Mingqing
Some studies have indicated that formaldehyde, a ubiquitous environmental pollutant, can induce or aggravate allergic asthma. Epidemiological studies have also shown that the relative humidity indoors may be an independent and a key factor associated with the aggravation of allergic asthma. However, the synergy of humidity and formaldehyde on allergic asthma and the mechanism underlying this effect remain largely unknown. In this study, we aim to determine the effect of high relative humidity and/or formaldehyde exposure on allergic asthma and explore the underlying mechanisms. Male Balb/c mice were modeled with ovalbumin (OVA) and exposure to 0.5 mg/m3 formaldehyde and/or different relative humidity (60%/75%/90%). Histopathological changes, pulmonary function, Th1/Th2 balance, the status of mucus hypersecretion and the levels of inflammatory factors were detected to assess the exacerbation of allergic asthma. The levels of the transient receptor potential vanilloid 4 (TRPV4), calcium ion and the activation of p38 mitogen-activated protein kinases (p38 MAPK) were detected to explore the underlying mechanisms. The results showed that exposure to high relative humidity or to 0.5 mg/m3 formaldehyde alone had a slight, but not significant, affect on allergic asthma. However, the pathological response and airway hyperresponsiveness (AHR) were greatly aggravated by simultaneous exposure to 0.5 mg/m3 formaldehyde and 90% relative humidity. Blocking TRPV4or p38 MAPK using HC-067047 and SB203580 respectively, effectively alleviated the exacerbation of allergic asthma induced by this simultaneous exposure to formaldehyde and high relative humidity. The results show that when formaldehyde and high relative humidity are present this can enhance the activation of the TRPV4 ion channel in the lung leading to the aggravation of the p38 MAPK activation, resulting in the exacerbation of inflammation and hypersecretion of mucus in the airways.
显示更多 [+] 显示较少 [-]Tricresyl phosphate isomers exert estrogenic effects via G protein-coupled estrogen receptor-mediated pathways
2020
Ji, Xiaoya | Li, Na | Ma, Mei | Rao, Kaifeng | Yang, Rong | Wang, Zijian
Tricresyl phosphates (TCPs), as representative aromatic organophosphate flame retardants (OPFRs), have received much attention due to their potential neurotoxicity and endocrine-disrupting effects. However, the role of estrogen receptor α (ERα) and G protein-coupled estrogen receptor (GPER) in their estrogen disrupting effects remains poorly understood. Therefore, in this study, three TCP isomers, tri-o-cresyl phosphate (ToCP), tri-m-cresyl phosphate (TmCP) and tri-p-cresyl phosphate (TpCP), were examined for their activities on ERα by using two-hybrid yeast assay, and action on GPER by using Boyden chamber assay, cAMP production assay, calcium mobilization assay and molecular docking analysis. The results showed that three TCP isomers were found to act as ERα antagonists. Conversely, they had agonistic activity on GPER to promote GPER-mediated cell migration of MCF7 cells and SKBR3 cells. Both ToCP and TpCP activated GPER-mediated cAMP production and calcium mobilization, whereas TmCP had different mode of action, it only triggered GPER-mediated calcium mobilization, as evidenced by using the specific GPER inhibitor (G15) and GPER overexpressing experiments. Molecular docking further revealed that the way of interaction of TmCP and TpCP with GPER was different from that of ToCP with GPER, and higher activity of ToCP in activating GPER-mediated pathways might be associated with the alkyl substitution at the ortho position of the aromatic ring. Our results, for the first time, found a new target, GPER, for TCPs exerting their estrogen-disrupting effects, and demonstrated complex estrogen-disrupting effects of three TCP isomers involved their opposite activities toward ERα and GPER.
显示更多 [+] 显示较少 [-]Selenium treatment modulates fluoride distribution and mitigates fluoride stress in tea plant (Camellia sinensis (L.) O. Kuntze)
2020
Niu, Huiliang | Zhan, Kui | Xu, Wei | Peng, Chuanyi | Hou, Chaoyuan | Li, Yeyun | Hou, Ruyan | Wan, Xiaochun | Cai, Huimei
Tea plants (Camellia sinensis (L.) O. Kuntze) can hyperaccumulate fluoride (F). The accumulation of F in tea leaves may induce serious health problems in tea consumers. It has been reported that selenium (Se) could reduce the accumulation of heavy metals in plants. Thus, the aim of this study was to investigate whether exogenous Se could reduce F accumulation in tea plant. The results showed that Se treatment could decrease F content in tea leaves, increase F accumulation in roots, decrease the proportion of water-soluble F in tea leaves and increase the Se content. Low F levels promoted the accumulation of Se in tea plants. Se treatment could modulate F-induced oxidative injury by decreasing malondialdehyde level and increasing the activities of superoxide dismutase, peroxidase and catalase. Moreover, Se inhibited F-induced increase in leaf iron, calcium, aluminum, leaf and root magnesium and lead contents. These results showed that Se application could decrease F content and increase Se content in tea leaves, which may be served as a novel strategy for production of healthy tea.
显示更多 [+] 显示较少 [-]Neodymium-containing contrast induces mummification of neutrophil granulocytes
2020
Pleskova, Svetlana | Kryukov, Ruslan | Boryakov, Alexey | Gorshkova, Ekaterina
Recently, chemical compounds containing lanthanides were used in various fields of biology and medicine. It has been described that such compounds can be applied in scanning electron microscopy (SEM) to increase the contrast and simplify the sample preparation process due to the process of replacing calcium with lanthanides in cell. However cell death by different mechanisms under influence of lanthanides seems possible. Here, we described that mummification process is a cell death physiologically realized in time: some time after lanthanide contrasting, the cell remains metabolically active and is able to biochemically transform neodymium-containing contrast, oxidize it and form large agglomerates. A distinctive feature of mummification induced by neodymium-containing contrast (NCC) is the formation of a high-rigid oxygen-containing “shield” on the surface of a neutrophil granulocyte.
显示更多 [+] 显示较少 [-]Insights into the regulation mechanisms of algal extracellular polymeric substances secretion upon the exposures to anatase and rutile TiO2 nanoparticles
2020
Gao, Xuan | Deng, Rui | Lin, Daohui
As an important part of extracellular secondary metabolites, extracellular polymeric substances (EPS) can play a significant role in protecting cells from the threat of exogenous substances, including nanoparticles (NPs). However, the regulation mechanisms of EPS secretion under NPs exposure remain largely unknown. This study investigated the signaling pathways and molecular responses related to EPS secretion of algae (Chlorella pyrenoidosa) upon the exposures to anatase and rutile TiO₂ NPs (nTiO₂-A and nTiO₂-R, respectively) at two similar toxic (20% and 50% of algal growth inhibition) concentrations. The results showed that EPS responded to nTiO₂ stress via excess secretion and compositional variation, and nTiO₂-A induced more EPS secretion than nTiO₂-R at similar toxicity concentrations. The up-regulation of the Ca²⁺ signaling pathway might play a greater role in promoting EPS secretion under nTiO₂-R exposure compared with nTiO₂-A exposure, while the significantly increased intracellular ROS could mainly account for the increased EPS secretion under nTiO₂-A exposure. The up-regulated genes related to biological synthesis and protein metabolism and the enhanced biosynthetic metabolism might be the direct causes of the increased EPS secretion. The increased ROS could have a greater effect on the amino acid metabolism and related genes upon the exposure to nTiO₂-A than nTiO₂-R to induce more EPS secretion. More serious membrane damage caused by nTiO₂-R than nTiO₂-A would affect the intracellular inositol phospholipid metabolism more severely, while the inositol phospholipid pathway and Ca²⁺ signaling pathway might agree and communicate with each other inherently to regulate EPS secretion upon nTiO₂-R exposure. The findings address the regulation mechanisms of algal EPS secretion under nTiO₂ exposure and provide new insights into algal bio-responses to nTiO₂ exposure.
显示更多 [+] 显示较少 [-]Etoxazole induces testicular malfunction in mice by dysregulating mitochondrial function and calcium homeostasis
2020
Epidemiological relationships between pesticide use and male infertility have been suggested for a long time. Etoxazole (ETX), an oxazoline pesticide, has been extensively used for pest eradication. It is considered relatively safe and has low mammalian toxicity because it specifically inhibits chitin synthesis. However, ETX may have toxic effects on the reproductive system. In this study, we examined the effects of ETX on the reproductive system using mouse testis cell lines (TM3 for Leydig cells and TM4 for Sertoli cells) and C57BL/6 male mice. We confirmed that ETX has anti-proliferative effects on the TM3 and TM4 cell lines. Moreover, ETX induced mitochondrial dysfunction and hampers calcium homeostasis. Western blot analysis of MAPK and Akt signaling cascades was performed to demonstrate the mode of action of ETX at a molecular level. Moreover, ETX induced misregulation of genes related to testicular function. Upon oral administration of ETX in C57BL/6 male mice, testis weight was reduced and transcriptional expression related to testis function was altered. These results indicate that ETX induces testicular toxicity by inducing mitochondrial dysfunction and calcium imbalance and regulating gene expression.
显示更多 [+] 显示较少 [-]Use of water quality index and multivariate statistical methods for the evaluation of water quality of a stream affected by multiple stressors: A case study
2020
Varol, Memet
The Sürgü Stream, located in the Euphrates River basin of Turkey, is used for drinking water source, agricultural irrigation and rainbow trout production. Therefore, water quality of the stream is of great importance. In this study, multivariate statistical techniques (MSTs) and water quality index (WQI) were applied to assess water quality of the stream affected by multiple stressors such as untreated domestic sewage, effluents from fish farms, agricultural runoff and streambank erosion. For this, 16 water quality parameters at five sites along the stream were monitored monthly during one year. Most of parameters showed significant spatial variations, indicating the influence of anthropogenic activities. All parameters except TN (total nitrogen) showed significant seasonal differences due to high seasonality in WT (water temperature) and water flow. The spatial variations in the WQI were significant (p < 0.05) and the mean WQI values ranged from 87.6 to 95.3, indicating “good” to “excellent” water quality in the stream. Cluster analysis classified five sites into three groups, that is, clean region, low polluted region and very clean region. Stepwise temporal discriminant analysis (DA) identified that pH, WT, Cl⁻, SO₄²⁻, COD (chemical oxygen demand), TSS (total suspended solids) and Ca²⁺ are the parameters responsible for variations between seasons, and stepwise spatial DA identified that DO (dissolved oxygen), EC (electrical conductivity), NH₄–N, TN (total nitrogen) and TSS are the parameters responsible for variations between the regions. Principal component analysis/factor analysis revealed that the parameters responsible for water quality variations were mainly associated with suspended solids (both natural and anthropogenic), soluble salts (natural) and nutrients and organic matter (anthropogenic).
显示更多 [+] 显示较少 [-]The influence of organic carbon on the toxicity of sediment-associated dinonylnaphthalene sulfonic acids to the benthic invertebrates Tubifex tubifex and Hyalella azteca
2020
Matten, K.J. | Bartlett, A.J. | Milani, D. | Gillis, P.L. | Parrott, J.L. | Toito, J. | Balakrishnan, V.K. | Prosser, R.S.
Naphthalene sulfonic acids (NSAs) are used extensively in industrial applications as dispersants in dyes, rubbers, and pesticides, and as anti-corrosive agents in coatings, gels, and sealants. This study examined the toxicity of three NSA congeners, barium dinonylnaphthalene sulfonate (BaDNS), calcium dinonylnaphthalene sulfonate (CaDNS), and dinonylnaphthalene disulfonic acid (DNDS), to two benthic species, Tubifex tubifex and Hyalella azteca. Two substrates with different levels of organic carbon (sediment [2%] and sand [0%]) were used in toxicity tests. Juvenile production was the most sensitive endpoint for T. tubifex: the 28-d EC50s were <18.2, 22.2, and 64.0 μg/g dw in sand and 281.3, 361.6, and 218.9 μg/g dw in sediment for BaDNS, CaDNS, and DNDS, respectively. The 28-d LC50s for H. azteca were similar among compounds: 115.3, 82.1, and 49.0 μg/g dry weight (dw) in sand, and 627.3, 757.9, and >188.5 μg/g dw in sediment, for BaDNS, CaDNS, and DNDS, respectively. However, when LC50s were estimated based on concentrations of NSAs measured in overlying water (which can be an important route of exposure for H. azteca), BaDNS and CaDNS were 3–4 orders of magnitude more toxic than DNDS. The NSAs examined were >3-fold more toxic when present in substrates with no organic carbon (e.g., sand) for all H. azteca endpoints where LC/EC50s could be calculated and for sublethal endpoints for T. tubifex. The organic carbon content of the sediment appears to have acted as a sink and reduced NSA toxicity by decreasing bioavailability. Environmental sediment samples were collected from 12 river sites across southern Ontario. The maximum concentration of CaDNS observed in sediment collected from this region was 2.8 μg/g dw in sediment with 2% organic carbon; 100-fold lower than the lowest EC10 in the current study.
显示更多 [+] 显示较少 [-]Toxicity of different forms of antimony to rice plants: Effects on reactive oxidative species production, antioxidative systems, and uptake of essential elements
2020
Zhu, Yanming | Wu, Qianhua | Lv, HaiQin | Chen, Wenxiang | Wang, Lizhen | Shi, ShengJie | Yang, JiGang | Zhao, PingPing | Li, Yuanping | Christopher, Rensing | Liu, Hong | Feng, RenWei
Antimonite [Sb(III)] and antimonate [Sb(V)] are known to have different toxicity to plants, but the corresponding mechanisms are not fully understood. This study was conducted to investigate reactive oxygen species (ROS), antioxidant systems, and levels of certain essential elements in response to exposure to Sb(III) and Sb(V). Results showed that exposure to Sb(V) caused oxidative stress in a rice plant (Yangdao No.6). Sb(III) was shown to be more toxic than Sb(V) as judged from a lower shoot biomass, a higher loss of essential elements, and higher production of superoxide anion free radicals (O₂⁻). The toxicity of Sb(III) might partially be due to the disturbance of the O₂ˉ dismutation reaction, which resulted in root cell membrane damage under exposure to 20 mg L⁻¹ Sb(III). Sb(V) stimulated the shoot fresh weight and the shoot uptake of many essential elements. Moreover, Sb(V) and Sb(III) both stimulated the accumulation of calcium in the shoots and roots, and calcium was found to significantly correlate with the concentrations of many essential elements and with some parameters correlated to antioxidant systems, suggesting a Ca-induced regulatory mechanism. The activity of glutathione peroxidase was significantly enhanced by Sb(V) and Sb(III), suggesting a role in scavenging hydrogen peroxide. Catalase was activated by exposure to 20 mg L⁻¹ Sb(III) in the roots and by exposure to 20 mg L⁻¹ Sb(V) both in the shoots and roots. However, peroxidase was activated by exposure to 5 mg L⁻¹ Sb(III) in the shoots and by exposure to 5 mg L⁻¹ Sb(V) in the roots. This study, for the first time, showed the differences between Sb(V) and Sb(III) toxicity when looking at the antioxidant response and essential element uptake.
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