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Multilayered glycoproteomic analysis reveals the hepatotoxic mechanism in perfluorooctane sulfonate (PFOS) exposure mice
2021
Li, Dapeng | Jiang, Lilong | Hong, Yanjun | Cai, Zongwei
Perfluorooctane sulfonate (PFOS) is one of the most widely used and distributed perfluorinated compounds proven to cause adverse health outcomes. Datasets of ecotoxico-genomics and proteomics have given greater insights for PFOS toxicological effect. However, the molecular mechanisms of hepatotoxicity of PFOS on post-translational modifications (PTMs) regulation, which is most relevant for regulating the activity of proteins, are not well elucidated. Protein glycosylation is one of the most ubiquitous PTMs associated with diverse cellular functions, which are critical towards the understanding of the multiple biological processes and toxic mechanisms exposed to PFOS. Here, we exploit the multilayered glycoproteomics to quantify the global protein expression levels, glycosylation sites, and glycoproteins in PFOS exposure and wild-type mouse livers. The identified 2439 proteins, 1292 glycosites, and 799 glycoproteins were displayed complex heterogeneity in PFOS exposure mouse livers. Quantification results reveal that 241 dysregulated proteins (fold change ≥ 2, p < 0.05) in PFOS exposure mouse livers were involved in the lipid and xenobiotic metabolism. While, 16 overexpressed glycoproteins were exclusively related to neutrophil degranulation, cellular responses to stress, protein processing in endoplasmic reticulum (ER). Moreover, the interactome and functional network analysis identified HP and HSP90AA1 as the potential glycoprotein biomarkers. These results provide unique insights into a deep understanding of the mechanisms of PFOS induced hepatotoxicity and liver disease. Our platform of multilayered glycoproteomics can be adapted to diverse ecotoxicological research.
Show more [+] Less [-]Insight into metabolism pathways of pesticide fomesafen in rice: Reducing cropping and environmental risks
2021
Chen, Zhao Jie | Qiao, Yu Xin | Zhang, Nan | Liu, Jintong | Yang, Hong
Fomesafen (FSA) is widely used in soybean fields for weed control. However, the persisting characteristics of FSA in the agricultural soil or water may become a hidden danger causing environmental pollution and phytotoxicity to succession crops. In this study, the growth and physiological responses of rice to FSA were investigated. It was found that the growth of rice seedlings was obviously inhibited by FSA exposure especially at over 0.1 mg L⁻¹. To gain an insight into the molecular mechanisms for the potential ecotoxicology, four libraries of rice roots and shoots exposed to FSA were created and subjected to the global RNA-sequencing (RNA-Seq) combined with HRLC-Q-TOF-MS/MS analytical technologies to comprehensively characterize the biochemical processes and catalytic reactions involved in FSA metabolism in rice. Compared with those without FSA, 499 and 450 up-regulated genes in roots and shoots with FSA were detected. Many of them were closely correlated with the tolerance to environmental stress, detoxification of xenobiotics and molecular metabolism process including cytochrome P450, glutathione S-transferases and acetyltransferase. A total of eight metabolites and fourteen conjugates in the reactive pathways of hydrolysis, substitution, reduction, methylation, glycosylation, acetylation, and malonylation were characterized by HRLC-Q-TOF-MS/MS. The relationship between the metabolized derivatives of FSA and enhanced expression the corresponding enzymatic regulators was established. This study will help understand the mechanisms and pathways of FSA metabolism and inspire the further research on FSA degradation in the paddy crops and environmental or health risks.
Show more [+] Less [-]Sulfur deficiency exacerbates phytotoxicity and residues of imidacloprid through suppression of thiol-dependent detoxification in lettuce seedlings
2021
Zhang, Nan | Huang, Lin | Zhang, Yuxue | Liu, Lijuan | Sun, Chengliang | Lin, Xianyong
Sulfur, an essential macronutrient, plays important roles in plant development and stress mitigation. Sulfur deficiency, a common problem in agricultural soils, may disturb plant stress resistance and xenobiotic detoxification. In the present study, the function and mechanism of limited sulfur nutrition on the residues and phtotoxicity of imidacloprid were investigated in lettuce plants. Sulfur deficiency significantly increased imidacloprid accumulation in lettuce tissues, exacerbated imidacloprid biological toxicity by enhancing the accumulation of toxic metabolites, like imidacloprid-olefin. Simultaneously, imidacloprid-induced detoxification enzymes including cytochromes P450, glutathione S-transferases (GSTs) and glycosyltransferases were inhibited under limited sulfur supply. On the other hand, sulfur deficiency further enhanced the generation of reactive oxygen species and exacerbated lipid peroxidation in lettuce tissues. Sulfur deficiency mainly reduced the abundance of thiol groups, which are essential redox modulators as well as xenobiotic conjugators, and significantly inhibited GSTs expression. These results clearly suggested that sulfur deficiency inhibited the synthesis of sulfur-containing compounds, leading to increased accumulation of pesticide residues and toxic metabolites as well as reduced detoxification capacity, consequently leading to oxidative damage to plants. Therefore, moderate sulfur supply in regions where neonicotinoid insecticides are intensively and indiscriminately used may be an efficient strategy to reduce pesticide residues and the potential risk to ecosystem.
Show more [+] Less [-]Repeated exposure to fungicide tebuconazole alters the degradation characteristics, soil microbial community and functional profiles
2021
Han, Lingxi | Kong, Xiabing | Xu, Min | Nie, Jiyun
Tebuconazole is a broad-spectrum triazole fungicide that has been extensively applied in agriculture, but its toxicity on soil ecology remains unknown after repeated introduction to soil. This study investigated the degradation of tebuconazole and the changes in soil microbial community composition and functional diversity as well as network complexity in soil repeatedly treated with tebuconazole. Tebuconazole degraded slowly as the degradation half-life initially increased and then decreased during the four repeated treatments. High concentration of tebuconazole treatment significantly delayed the degradation of tebuconazole. The soil microbial functional diversity in tebuconazole-treated soils showed an inhibition-recovery-stimulation trend with increasing treatment frequency, which was related to the increased degradation rates of tebuconazole. Tebuconazole significantly decreased soil microbial biomass and bacterial community diversity, and this decreasing trend became more pronounced with increasing treatment frequency and concentration. Moreover, tebuconazole significantly decreased soil bacterial community network complexity, particularly at high concentration of tebuconazole treatment. Notably, four bacterial genera, Methylobacterium, Burkholderia, Hyphomicrobium, and Dermacoccus, were identified as the potential tebuconazole-degrading bacteria, with the relative abundances in the tebuconazole treatment significantly increasing by 42.1–34687.1% compared to the control. High concentration of tebuconazole treatment delayed increases in the relative abundances of Methylobacterium but promoted those of Burkholderia, Hyphomicrobium and Dermacoccus. Additionally, repeated tebuconazole treatments improved only four metabolic pathways, cell motility, membrane transport, environmental information processing, and xenobiotics biodegradation and metabolism, which were associated with the degradation of tebuconazole. The above results indicated that repeated tebuconazole treatments resulted in the significant accumulation of residues and long-term negative effects on soil ecology, and also emphasized the potential roles of dominant indigenous microbial bacteria in the degradation of tebuconazole.
Show more [+] Less [-]Trophic transfer, bioaccumulation and transcriptomic effects of permethrin in inland silversides, Menidia beryllina, under future climate scenarios
2021
Derby, Andrew P. | Fuller, Neil W. | Huff Hartz, Kara E. | Segarra, Amelie | Connon, Richard E. | Brander, Susanne M. | Lydy, Michael J.
Global climate change (GCC) significantly affects aquatic ecosystems. Continual use of pyrethroid insecticides results in contamination of these ecosystems and concurrent GCC raises the potential for synergistic effects. Resistance to pyrethroids has been documented in Hyalella azteca, a common epibenthic amphipod and model organism. Resistant H. azteca can bioconcentrate elevated amounts of pyrethroids and represent a threat to consumers via trophic transfer. In the present study, a predator of H. azteca, the inland silverside (Menidia beryllina), was used to examine the impacts of GCC on pyrethroid bioaccumulation via trophic transfer from resistant prey organisms. M. beryllina were fed ¹⁴C-permethrin dosed pyrethroid-resistant H. azteca for 14 days at three salinities (6, 13 and 20 practical salinity units (PSU)) and two temperatures (18 and 23 °C). Fish were analyzed for total body residues, percent parent compound and percent metabolites. Gene expression in liver and brain tissue were evaluated to assess whether dietary bioaccumulation of permethrin would impact detoxification processes, metabolism, and general stress responses. M. beryllina bioaccumulated significant amounts of permethrin across all treatments, ranging from 39 to 557 ng g⁻¹ lipid. No statistically significant effect of temperature was found on total bioaccumulation. Salinity had a significant effect on total bioaccumulation, owing to greater bioaccumulation at 6 PSU compared to 13 and 20 PSU, which may be due to alterations to xenobiotic elimination. Permethrin bioaccumulation and the interaction with temperature and salinity elicited significant transcriptional responses in genes relating to detoxification, growth, development, and immune response. Given the increased prevalence of pesticide-resistant aquatic invertebrates, GCC-induced alterations to temperature and salinity, and the predicted increase in pesticide usage, these findings suggest trophic transfer may play an important role in pesticide bioaccumulation and effects in predatory fish.
Show more [+] Less [-]Suspended solids-associated toxicity of hydraulic fracturing flowback and produced water on early life stages of zebrafish (Danio rerio)
2021
Lü, Yichun | Zhang, Yifeng | Zhong, Cheng | Martin, Jonathan W. | Alessi, Daniel S. | Goss, Greg G. | Ren, Yuan | He, Yuhe
Hydraulic fracturing flowback and produced water (HF-FPW), which contains polyaromatic hydrocarbons (PAHs) and numerous other potential contaminants, is a complex wastewater produced during the recovery of tight hydrocarbon resources. Previous studies on HF-FPW have demonstrated various toxicological responses of aquatic organisms as consequences of combined exposure to high salinity, dissolved organic compounds and particle/suspended solids-bound pollutants. Noteworthy is the lack of studies illustrating the potentially toxic effects of the FPW suspended solids (FPW-SS). In this study, we investigated the acute and sublethal toxicity of suspended solids filtered from six authentic FPW sample collected from two fracturing wells, using a sediment contact assay based on early-life stages of zebrafish (Danio rerio). PAHs profiles and acute toxicity tests provided initial information on the toxic potency of the six samples. Upon exposure to sediment mixture at two selected doses (1.6 and 3.1 mg/mL), results showed adverse effects in larval zebrafish, as revealed by increased Ethoxyresorufin-O-deethylase (EROD) activity. Transcriptional alterations were also observed in xenobiotic biotransformation (ahr, pxr, cyp1a, cyp1b1, cyp1c1, cyp1c2, cyp3a65, udpgt1a1, udpgt5g1), antioxidant response (sod1, sod2, gpx1a, gpx1b) and hormone receptor signaling (esr1, esr2a, cyp19a1a, vtg1) genes. The results demonstrated that even separated from the complex aqueous FPW mixture, FPW-SS can induce toxicological responses in aquatic organisms' early life stages. Since FPW-SS could sediment to the bottom of natural wetland acting as a continuous source of contaminants, the current findings imply the likelihood of long-term environmental risks of polluted sediments on aquatic ecosystems due to FPW spills.
Show more [+] Less [-]Lycopene prevents DEHP-induced hepatic oxidative stress damage by crosstalk between AHR–Nrf2 pathway
2021
Zhao, Yi | Bao, Rong-Kun | Zhu, Shi-Yong | Talukder, Milton | Cui, Jia-Gen | Zhang, Hao | Li, Xue-Nan | Li, Jin-Long
Di (2-ethylhexyl) phthalate (DEHP) is a widespread plasticizer that persists in the environment and can significantly contribute to serious health hazards of liver especially oxidative stress injury. Lycopene (LYC) as a carotenoid has recently gained widespread attention because of antioxidant activity. However, the potential mechanism of DEHP-induced hepatotoxicity and antagonism effect of LYC on it are still unclear. To explore the underlying mechanisms of this hypothesis, the mice were given by gavage with LYC (5 mg/kg) and DEHP (500 or 1000 mg/kg). The data suggested that DEHP caused liver enlargement, reduction of antioxidant activity markers, increase of oxidative stress indicators and disorder of cytochrome P450 enzymes system (CYP450s) homeostasis. DEHP-induced reactive oxygen species (ROS) activated the NF-E2-relatedfactor2 (Nrf2) and nuclear xenobiotic receptors (NXRs) system including Aryl hydrocarbon receptor (AHR), Pregnane X receptor (PXR) and Constitutive androstane receptor (CAR). Interestingly, these disorders and injuries were prevented after LYC treatment. Taken together, DEHP administration resulted in hepatotoxicity including oxidative stress injury and disordered CYP450 system, but these alterations might be ameliorated by LYC via crosstalk between AHR–Nrf2 pathway.
Show more [+] Less [-]Chronic pesticide exposure induced aberrant Notch signalling along the visual pathway in a murine model
2021
Sanyal, Shalini | Law, Sujata
Pesticides aid in crop-protection against pests and increase yield. However, the xenobiotic stress exerted by pesticides leads to the deterioration of human and animal health. There is a lacuna in our knowledge about their impact on the ocular surface The present work sheds light on this gap by analysing the deterioration of visual acuity as a consequence of pesticide induced xenobiotic stress and Notch pathway dysregulation.Alteration in the expression of vital components of the notch signalling was analyzed along the visual pathway with special focus on its two terminals-the cornea and the visual cortex, by mimicking the on-field scenario regarding chronic pesticide exposure in experimental murine model (Swiss albino mice; Mus musculus). Various aspects were taken into consideration through visual acuity tests, histological evaluations, culture analyses, wound healing assays, flowcytometric evaluation, fluorescence microscopic studies etc. Complete dysregulation of key players of the Notch signalling pathway was observed in both: cells of the ocular surface as well as those in the murine visual cortex post pesticide exposure, indicating activities relating to cell proliferation, differentiation and wound healing in the pesticide exposed samples. Ultra-microscopic analyses corroborated our findings by revealing the loss of fine neural processes in the visual cortex of the pesticide exposed murine samples, thereby hinting at delayed perception to visual stimuli. In vivo evaluations of the functional capacity of the neuroanatomical structures along the visual pathway also confirmed that pesticide exposure leads to severe damage along the various parts of the visual pathway, right from the ocular surface to the visual cortex.
Show more [+] Less [-]Tracking gene expression, metabolic profiles, and biochemical analysis in the halotolerant basidiomycetous yeast Rhodotorula mucilaginosa EXF-1630 during benzo[a]pyrene and phenanthrene biodegradation under hypersaline conditions
2021
Martínez-Ávila, Liliana | Peidro-Guzmán, Heidy | Pérez-Llano, Yordanis | Moreno Perlín, Tonatiuh | Sánchez-Reyes, Ayixon | Aranda, Elisabet | Ángeles de Paz, Gabriela | Fernández-Silva, Arline | Folch-Mallol, Jorge Luis | Cabana, Hubert | Gunde-Cimerman, Nina | Batista-García, Ramón Alberto
Polyaromatic phenanthrene (Phe) and benzo[a]pyrene (BaP) are highly toxic, mutagenic, and carcinogenic contaminants widely dispersed in nature, including saline environments. Polyextremotolerant Rhodotorula mucilaginosa EXF-1630, isolated from Arctic sea ice, was grown on a huge concentration range -10 to 500 ppm- of Phe and BaP as sole carbon sources at hypersaline conditions (1 M NaCl). Selected polycyclic aromatic hydrocarbons (PAHs) supported growth as well as glucose, even at high PAH concentrations. Initially, up to 40% of Phe and BaP were adsorbed, followed by biodegradation, resulting in 80% removal in 10 days. While extracellular laccase, peroxidase, and un-specific peroxygenase activities were not detected, NADPH-cytochrome c reductase activity peaked at 4 days. The successful removal of PAHs and the absence of toxic metabolites were confirmed by toxicological tests on moss Physcomitrium patens, bacterium Aliivibrio fischeri, human erythrocytes, and pulmonary epithelial cells (A549). Metabolic profiles were determined at the midpoint of the biodegradation exponential phase, with added Phe and BaP (100 ppm) and 1 M NaCl. Different hydroxylated products were found in the culture medium, while the conjugative metabolite 1-phenanthryl-β-D-glucopyranose was detected in the medium and in the cells. Transcriptome analysis resulted in 870 upregulated and 2,288 downregulated transcripts on PAHs, in comparison to glucose. Genomic mining of 61 available yeast genomes showed a widespread distribution of 31 xenobiotic degradation pathways in different yeast lineages. Two distributions with similar metabolic capacities included black yeasts and mainly members of the Sporidiobolaceae family (including EXF-1630), respectively. This is the first work describing a metabolic profile and transcriptomic analysis of PAH degradation by yeast.
Show more [+] Less [-]Moxidectin toxicity to zebrafish embryos: Bioaccumulation and biomarker responses
2021
Muniz, Marta Silva | Halbach, Katharina | Alves Araruna, Igor Cauê | Martins, Rafael Xavier | Seiwert, Bettina | Lechtenfeld, Oliver | Reemtsma, Thorsten | Farias, Davi
Moxidectin is an antiparasitic drug belonging to the class of the macrocyclic lactones, subgroup mylbemicins. It is used worldwide in veterinary practice, but little is known about its potential environmental risks. Thus, we used the zebrafish embryo as a model system to study the potential effects of moxidectin on aquatic non-target organisms. The analyses were performed in two experimental sets: (1) acute toxicity and apical endpoints were characterized, with biomarker assays providing information on the activity levels of catalase (CAT), glutathione S-transferase (GST), lactate dehydrogenase (LDH), and acetylcholinesterase (AChE); and (2) internal concentration and spatial distribution of moxidectin were determined using ultraperformance liquid chromatography quadrupole-time-of-flight mass spectrometry (UPLC-QToF-MS) and matrix-assisted laser desorption/ionization-MS imaging (MALDI-MSi). The acute toxicity to zebrafish embryos (96 hpf) appeared mainly as a decrease in hatching rates (EC₅₀ = 20.75 μg/L). It also altered the enzymatic activity of biomarker enzymes related to xenobiotic processing, anaerobic metabolism, and oxidative stress (GST, LDH, and CAT, respectively) and strongly accumulated in the embryos, as internal concentrations were 4 orders of magnitude higher than those detected in exposure solutions. MALDI-MSi revealed accumulations of the drug mainly in the head and eyes of the embryos (72 and 96 hpf). Thus, our results show that exposure to moxidectin decreases hatching success by 96 h and alters biochemical parameters in the early life stages of zebrafish while accumulating in the head and eye regions of the animals, demonstrating the need to prioritize this compound for environmental studies.
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