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Size-dependent impact of polystyrene microplastics on the toxicity of cadmium through altering neutrophil expression and metabolic regulation in zebrafish larvae
2021
Qin, Li | Duan, Zhenghua | Cheng, Haodong | Wang, Yudi | Zhang, Haihong | Zhu, Zhe | Wang, Lei
Insufficient evidence exists regarding the visible physiological toxic endpoints of MPs exposures on zebrafish larvae due to their small sizes. Herein, the impacts of micro-polystyrene particles (μ-PS) and 100 nm polystyrene particles (n-PS) on the toxicity of cadmium (Cd) through altering neutrophil expressions were identified and quantified in the transgenic zebrafish (Danio rerio) larvae Tg(lyz:DsRed2), and the effects were size-dependent. When exposed together with μ-PS, the amount of neutrophils in Cd treated zebrafish larvae decreased by 25.56% through reducing Cd content in the larvae. By contrast, although n-PS exposure caused lower Cd content in the larvae, the expression of neutrophils under their combined exposure remained high. The mechanism of immune toxicity was analyzed based on the results of metabonomics. n-PS induced high oxidative stress in the larvae, which promoted taurine metabolism and unsaturated fatty biosynthesis in n-PS + Cd treatment. This observation was accordance with the significant inhibition of the activities of superoxide dismutase and catalase enzymes detected in their combined treatment. Moreover, n-PS promoted the metabolic pathways of catabolic processes, amino acid metabolism, purine metabolism, and steroid hormone biosynthesis in Cd treated zebrafish larvae. Nanoplasctis widely coexist with other pollutants in the environment at relatively low concentrations. We conclude that more bio-markers of immune impact should be explored to identify their toxicological mechanisms and mitigate the effects on the environment.
Afficher plus [+] Moins [-]Mechanism of thorium-nitrate and thorium-dioxide induced cytotoxicity in normal human lung epithelial cells (WI26): Role of oxidative stress, HSPs and DNA damage
2021
Das, Sourav Kumar | Ali, Manjoor | Shetake, Neena G. | Dumpala, Rama Mohan R. | Pandey, Badri N. | Kumar, Amit
Inhalation represents the most prevalent route of exposure with Thorium-232 compounds (Th-nitrate/Th-dioxide)/Th-containing dust in real occupational scenario. The present study investigated the mechanism of Th response in normal human alveolar epithelial cells (WI26), exposed to Th-nitrate or colloidal Th-dioxide (1–100 μg/ml, 24–72 h). Assessment in terms of changes in cell morphology, cell proliferation (cell count), plasma membrane integrity (lactate dehydrogenase leakage) and mitochondrial metabolic activity (MTT reduction) showed that Th-dioxide was quantitatively more deleterious than Th-nitrate to WI26 cells. TEM and immunofluorescence analysis suggested that Th-dioxide followed a clathrin/caveolin-mediated endocytosis, however, membrane perforation/non-endocytosis seemed to be the mode of Th internalization in cells exposed to Th-nitrate. Th-estimation by ICP-MS showed significantly higher uptake of Th in cells treated with Th-dioxide than with Th-nitrate at a given concentration. Both Th-dioxide and nitrate were found to increase the level of reactive oxygen species, which seemed to be responsible for lipid peroxidation, alteration in mitochondrial membrane potential and DNA-damage. Amongst HSPs, the protein levels of HSP70 and HSP90 were affected differentially by Th-nitrate/dioxide. Specific inhibitors of ATM (KU55933) or HSP90 (17AAG) were found to increase the Th- cytotoxicity suggesting prosurvival role of these signaling molecules in rescuing the cells from Th-toxicity.
Afficher plus [+] Moins [-]Long-term toxicity of lindane through oxidative stress and cell apoptosis in Caenorhabditis elegans
2021
Yu, Yunjiang | Chen, Haibo | Hua, Xin | Wang, Zheng-Dong | Li, Liangzhong | Li, Zongrui | Xiang, Mingdeng | Ding, Ping
Lindane persists in the environment and bioaccumulates as an organochlorine pesticide and can pose risks to ecological environments and human health. To explore the long-term toxicity and underlying mechanisms of lindane, Caenorhabditis elegans was chosen as an animal model for toxicological study. The indicators of physiological, oxidative stress and cell apoptosis were examined in nematodes chronically exposed to environmentally relevant concentrations of lindane (0.01–100 ng/L). The data suggested that exposure to lindane at doses above 0.01 ng/L induced adverse physiological effects in C. elegans. Significant increases of ROS production and lipofuscin accumulation were observed in 100 ng/L of lindane-exposed nematodes, suggesting that lindane exposure induced oxidative stress in nematodes. Exposure to 10–100 ng/L of lindane also significantly increased the average number of germ cell corpses, which indicated cell apoptosis induced by lindane in C. elegans. Moreover, chronic exposure to 100 ng/L lindane significantly influenced the expression of genes related to oxidative stress and cell apoptosis (e.g., isp-1, sod-3, ced-3, and cep-1 genes). These results indicated that oxidative stress and cell apoptosis could play an important role in toxicity induced by lindane in nematodes.
Afficher plus [+] Moins [-]Toxicity and fate of chiral insecticide pyriproxyfen and its metabolites in zebrafish (Danio rerio)
2021
Wei, Yimu | Cui, Jingna | Zhai, Wangjing | Liu, Xueke | Zhou, Zhiqiang | Wang, Peng | Liu, Donghui
Pyriproxyfen is a juvenile hormone analogue insecticide used worldwide. At present, the potential threat of pyriproxyfen to aquatic organism has not been well explored. In this work, the bioaccumulation, metabolic profile and toxicity of pyriproxyfen and its metabolites to zebrafish were studied, and the enantioselectivity of pyriproxyfen and the major chiral metabolites were also determined. Sixteen metabolites of pyriproxyfen in zebrafish were identified. Hydroxylation, ether linkage cleavage and oxidation in phase I metabolism, followed by sulfate and glucuronic acid conjugation. The bioconcentration factors ranged from 1175 to 1246. Hydroxylation metabolites of pyriproxyfen showed enantioselective behavior in zebrafish with enantiomer fractions (EFs) of 4′–OH– pyriproxyfen and 5″–OH– pyriproxyfen ranged from 0.50 to 0.71. Toxicological indexes including acute toxicity, joint toxicity and oxidative stress were tested. Among all the metabolites, 4′–OH– pyriproxyfen was found 2 folds more toxic to zebrafish than pyriproxyfen. (−)-Pyriproxyfen was found 2 folds more toxic than rac- and (+)-pyriproxyfen. Antagonistic effects were found in binary joint toxicity of pyriproxyfen and its hydroxylated metabolites. Pyriproxyfen and its metabolites also showed oxidative stress damage by inhibiting the activity of CAT and SOD and increasing MDA. This work provided deep insight into the metabolism and the potential risks of pyriproxyfen to aquatic organisms.
Afficher plus [+] Moins [-]PAHs in an urban-industrial area: The role of lichen transplants in the detection of local and study area scale patterns
2021
Lucadamo, L. | Gallo, L. | Corapi, A.
Spatial variation of the levels of polycyclic aromatic hydrocarbons (PAHs) was evaluated within an urban-industrial district where the main anthropogenic pressures are a 15 MW biomass power plant (BPP) and road traffic. The use of a high-density lichen transplant network and wind quantitative relationships made it possible to perform a hierarchical analysis of contamination. Combined uni-bi and multivariate statistical analyses of the resulting databases revealed a dual pattern. In its surroundings (local scale), the BPP affected the bioaccumulation of fluoranthene, pyrene and total PAHs, although a confounding effect of traffic (mostly petrol/gasoline engines) was evident. Spatial variation of the rate of diesel vehicles showed a significant association with that of acenaphthylene, acenaphthene, fluorene, anthracene and naphthalene. The series of high-speed wind values suggests that wind promotes diffusion rather than dispersion of the monitored PAHs. At the whole study area scale, the BPP was a source of acenaphthylene and acenaphthene, while diesel vehicles were a source of acenaphthylene. PAHs contamination strongly promotes oxidative stress (a threefold increase vs pre-exposure levels) in lichen transplants, suggesting a marked polluting effect of anthropogenic sources especially at the expense of the mycobiont. The proposed monitoring approach could improve the apportionment of the different contributions of point and linear anthropogenic sources of PAHs, mitigating the reciprocal biases affecting their spatial patterns.
Afficher plus [+] Moins [-]Thioredoxin-albumin fusion protein prevents urban aerosol-induced lung injury via suppressing oxidative stress-related neutrophil extracellular trap formation
2021
Tanaka, Ken-ichiro | Kubota, Maho | Shimoda, Mikako | Hayase, Tomoko | Miyaguchi, Mamika | Kobayashi, Nahoko | Ikeda, Mayumi | Ishima, Yu | Kawahara, Masahiro
The number of deaths from air pollution worldwide is estimated at 8.8 million per year, more than the number of deaths from smoking. Air pollutants, such as PM₂.₅, are known to induce respiratory and cardiovascular diseases by inducing oxidative stress. Thioredoxin (Trx) is a 12-kDa endogenous protein that exerts antioxidant activity by promoting dithiol disulfide exchange reactions. We previously synthesized human serum albumin-fused thioredoxin (HSA-Trx), which has a longer half-life in plasma compared with Trx, and demonstrated its efficacy against various diseases including respiratory diseases. Here, we examined the effect of HSA-Trx on urban aerosol-induced lung injury in mice. Urban aerosols induced lung injury and inflammatory responses in ICR mice, but intravenous administration of HSA-Trx markedly inhibited these responses. We next analyzed reactive oxygen species (ROS) production in murine lungs using an in vivo imaging system. The results show that intratracheal administration of urban aerosols induced ROS production that was inhibited by intravenously administered HSA-Trx. Finally, we found that HSA-Trx inhibited the urban aerosol-induced increase in levels of neutrophilic extracellular trap (NET) indicators (i.e., double-stranded DNA, citrullinated histone H3, and neutrophil elastase) in bronchoalveolar lavage fluid (BALF). Together, these findings suggest that HSA-Trx prevents urban aerosol-induced acute lung injury by suppressing ROS production and neutrophilic inflammation. Thus, HSA-Trx may be a potential candidate drug for preventing the onset or exacerbation of lung injury caused by air pollutants.
Afficher plus [+] Moins [-]Application of the in vivo oxidative stress reporter Hmox1 as mechanistic biomarker of arsenic toxicity
2021
Inesta-Vaquera, Francisco | Navasumrit, Panida | Henderson, Colin J. | Frangova, Tanya G. | Honda, Tadashi | Dinkova-Kostova, Albena T. | Ruchirawat, Mathuros | Wolf, C Roland
Inorganic arsenic (iAs) is a naturally occurring metalloid present in drinking water and polluted air exposing millions of people globally. Epidemiological studies have linked iAs exposure to the development of numerous diseases including cognitive impairment, cardiovascular failure and cancer. Despite intense research, an effective therapy for chronic arsenicosis has yet to be developed. Laboratory studies have been of great benefit in establishing the pathways involved in iAs toxicity and providing insights into its mechanism of action. However, the in vivo analysis of arsenic toxicity mechanisms has been difficult by the lack of reliable in vivo biomarkers of iAs’s effects. To address this issue we have applied the use of our recently developed stress reporter models to study iAs toxicity. The reporter mice Hmox1 (oxidative stress/inflammation; HOTT) and p21 (DNA damage) were exposed to iAs at acute and chronic, environmentally relevant, doses. We observed induction of the oxidative stress reporters in several cell types and tissues, which was largely dependent on the activation of transcription factor NRF2. We propose that our HOTT reporter model can be used as a surrogate biomarker of iAs-induced oxidative stress, and it constitutes a first-in-class platform to develop treatments aimed to counteract the role of oxidative stress in arsenicosis. Indeed, in a proof of concept experiment, the HOTT reporter mice were able to predict the therapeutic utility of the antioxidant N-acetyl cysteine in the prevention of iAs associated toxicity.
Afficher plus [+] Moins [-]Potamopyrgus antipodarum has the potential to detect effects from various land use activities on a freshwater ecosystem
2021
Subba, Maita | Keough, Michael J. | Kellar, Claudette | Roth, Sara Long | Miranda, Ana | Pettigrove, Vincent J.
Identifying risks to ecosystems from contaminants needs a diversity of bioindicators, to understand the effects of these contaminants on a range of taxa. Molluscs are an ideal bioindicator because they are one of the largest phyla with extremely high ecological and economic importance. The aim of this study was to evaluate if laboratory bred Potamopyrgus antipodarum has the potential to show the impact of contaminants from various land use activities and degree of pollution on a freshwater ecosystem. We assessed the impact of contaminants arising from runoff and direct discharges in Merri Creek by measuring organism level responses (survival, growth, and reproduction), and sub-organism level responses (glutathione S-transferase (GST) activity, lipid peroxidation (LPO) activity and catalase (CAT) activity) in snails after 28-d of deployment at nine sites in Merri Creek and one site in Cardinia Creek. In Merri Creek, the top two sites were reference sites (with low impact from human activities), while the rest were impact sites (impacted by various anthropogenic land uses). Cardinia Creek (an additional reference site) had lower human activity. High concentrations of heavy metals, nutrients, and/or synthetic pyrethroids (bifenthrin) dominated these sites, which are likely to have contributed towards the negative responses observed in the snails. There was little influence from environmental conditions and site location on the endpoints because we found a similar response at an additional reference site compared to the reference sites in Merri Creek. At the organism level, reproduction increased and/or reduced, while CAT was affected at the sub-organism level. Potamopyrgus antipodarum has the potential to be a sensitive bioindicator for Australian conditions because the snails responded to varying concentrations of contaminants across different land use activities and showed similar sensitivity to P. antipodarum found in other regions of the globe and other bioindicators.
Afficher plus [+] Moins [-]Biomarkers-based assessment of triclosan toxicity in aquatic environment: A mechanistic review
2021
Kumar, Saurav | Paul, Tapas | Shukla, S.P. | Kundan Kumar, | Karmakar, Sutanu | Bera, Kuntal Krishna | Bhushan kumar, Chandra
Triclosan (TCS), an emergent pollutant, is raising a global concern due to its toxic effects on organisms and aquatic ecosystems. The non-availability of proven treatment technologies for TCS remediation is the central issue stressing thorough research on understanding the underlying mechanisms of toxicity and assessing vital biomarkers in the aquatic organism for practical monitoring purposes. Given the unprecedented circumstances during COVID 19 pandemic, a several-fold higher discharge of TCS in the aquatic ecosystems cannot be considered a remote possibility. Therefore, identifying potential biomarkers for assessing chronic effects of TCS are prerequisites for addressing the issues related to its ecological impact and its monitoring in the future. It is the first holistic review on highlighting the biomarkers of TCS toxicity based on a comprehensive review of available literature about the biomarkers related to cytotoxicity, genotoxicity, hematological, alterations of gene expression, and metabolic profiling. This review establishes that biomarkers at the subcellular level such as oxidative stress, lipid peroxidation, neurotoxicity, and metabolic enzymes can be used to evaluate the cytotoxic effect of TCS in future investigations. Micronuclei frequency and % DNA damage proved to be reliable biomarkers for genotoxic effects of TCS in fishes and other aquatic organisms. Alteration of gene expression and metabolic profiling in different organs provides a better insight into mechanisms underlying the biocide's toxicity. In the concluding part of the review, the present status of knowledge about mechanisms of antimicrobial resistance of TCS and its relevance in understanding the toxicity is also discussed referring to the relevant reports on microorganisms.
Afficher plus [+] Moins [-]Environmentally relevant concentration of sulfamethoxazole-induced oxidative stress-cascaded damages in the intestine of grass carp and the therapeutic application of exogenous lycopene
2021
Wang, Yu | Zhao, Hongjing | Liu, Yachen | Li, Jingyan | Nie, Xiaopan | Huang, Puyi | Xing, Mingwei
Due to the unreasonable use and discharge of the aquaculture industry, over standard of the antibiotics has been frequent in different types of water environments, causing adverse effects on aquatic organisms. Lycopene (LYC) is an esculent carotenoid, which is considered to be a strong antioxidant. This study was designed to explore the therapeutic effect of LYC on antibiotic (sulfamethoxazole (SMZ)) induced intestinal injury in grass carp Ctenopharyngodon idella. The 120 carps (the control, LYC, SMZ, and co-administration groups) were treated for 30 days. We found that treatment with LYC significantly suppressed SMZ-induced intestinal epithelial cell damage and tight junction protein destruction through histopathological observation, transmission electron microscopy and detection of related genes (Claudin-1/3/4, Occludin and zonula occludens (ZO)-1/2). Furthermore, LYC mitigated SMZ-induced dysregulation of oxidative stress markers, including elevated malondialdehyde (MDA) levels, and consumed super oxide dimutese (SOD), catalase (CAT) activities and glutathione (GSH) content. In the same treatment, LYC reduced inflammation and apoptosis by a detectable change in pro-inflammatory factors (tumor necrosis factor-alpha (TNF-β), interleukin (IL)-1β, IL-6 and IL-8), anti-inflammatory factors (transforming growth factor-beta (TGF-β) and IL-10) and pro-apoptosis related genes (p53, p53 upregulated modulator of apoptosis (PUMA), Bax/Bcl-2 ratio, caspase-3/9). In addition, activation of autophagy (as indicated by increased autophagy-related genes through AMPK/ATK/MTOR signaling pathway) under the stress of SMZ was also dropped back to the original levels by LYC co-administration. Collectively, our findings identified that LYC can serve as a protectant agent against SMZ-induced intestinal injury.
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