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Chronic exposure to a pervasive pharmaceutical pollutant erodes among-individual phenotypic variation in a fish
2020
Shan, Hong | Polverino, Giovanni | Martin, Jake M. | Bertram, Michael G. | Wiles, Sarah C. | Palacios, Maria M. | Bywater, Candice L. | White, Craig R. | Wong, Bob B.M.
Pharmaceutical pollution is now recognised as a major emerging agent of global change. Increasingly, pharmaceutical pollutants are documented to disrupt ecologically important physiological and behavioural traits in exposed wildlife. However, little is known about potential impacts of pharmaceutical exposure on among-individual variation in these traits, despite phenotypic diversity being critical for population resilience to environmental change. Furthermore, although wildlife commonly experience multiple stressors contemporaneously, potential interactive effects between pharmaceuticals and biological stressors—such as predation threat—remain poorly understood. To redress this, we investigated the impacts of long-term exposure to the pervasive pharmaceutical pollutant fluoxetine (Prozac®) on among-individual variation in metabolic and behavioural traits, and the combined impacts of fluoxetine exposure and predation threat on mean metabolic and behavioural traits in a freshwater fish, the guppy (Poecilia reticulata). Using a mesocosm system, guppy populations were exposed for 15 months to one of two field-realistic levels of fluoxetine (nominal concentrations: 30 and 300 ng/L) or a solvent control. Fish from these populations were then tested for metabolic rate (oxygen uptake) and behaviour (activity), both before and after experiencing one of three levels of a predation treatment: an empty tank, a non-predatory fish (Melanotaenia splendida) or a predatory fish (Leiopotherapon unicolor). Guppies from both fluoxetine treatments had ∼70% lower among-individual variation in their activity levels, compared to unexposed fish. Similarly, fluoxetine exposure at the higher dosage was associated with a significant (26%) reduction in individual-level variation in oxygen uptake relative to unexposed fish. In addition, mean baseline metabolic rate was disrupted in low-fluoxetine exposed fish, although mean metabolic and behavioural responses to predation threat were not affected. Overall, our study demonstrates that long-term exposure to a pervasive pharmaceutical pollutant alters ecologically relevant traits in fish and erodes among-individual variability, which may be detrimental to the stability of contaminated populations globally.
显示更多 [+] 显示较少 [-]Transcriptome alterations in female Daphnia (Daphnia magna) exposed to 17β-estradiol
2020
Zheng, Yao | Yuan, Julin | Gu, Zhimin | Yang, Guang | Li, Tian | Chen, Jiazhang
The molecular mechanism of evaluating 17β-estradiol (E₂)-induced toxicity in female Daphnia magna has not been determined. In this study, the transcriptome of D. magna was analyzed after exposure to three different concentrations (0, 10, and 100 ng L⁻¹) of E₂ at 3, 6, and 12 h. The results showed 351–17,221 significantly up-regulated and 505–10,282 significantly down-regulated genes (P < 0.05). Overall, the selected largest 10,282 (10 ng L⁻¹vs control at 12 h) down-regulated and 17,221 (100 vs 10 ng L⁻¹) up-regulated genes were identified; following annotation, pathways in cancer and RNA transport were found to be enriched according to the interaction network. Among all completed comparisons, KEGG pathways related to the immune system, cancer, disease infection, and active compound metabolism were identified by short time series expression miner analysis. A different set of genes fluctuated in a “U”-shaped pattern over time and at different concentrations of E₂, whereas some genes associated with disintoxication showed a reverse “U”-shaped response as E₂ administration was increased. These results suggest that E₂ exposure caused transcriptional changes in the immune system, disintoxication, disease prevention, and the protein degradation pathway.
显示更多 [+] 显示较少 [-]Genotoxicity and DNA damage signaling in response to complex mixtures of PAHs in biomass burning particulate matter from cashew nut roasting
2020
Approximately 3 billion people world-wide are exposed to air pollution from biomass burning. Herein, particulate matter (PM) emitted from artisanal cashew nut roasting, an important economic activity worldwide, was investigated. This study focused on: i) chemical characterization of polycyclic aromatic hydrocarbons (PAHs) and oxygenated (oxy-) PAHs; ii) intracellular levels of reactive oxygen species (ROS); iii) genotoxic effects and time- and dose-dependent activation of DNA damage signaling, and iv) differential expression of genes involved in xenobiotic metabolism, inflammation, cell cycle arrest and DNA repair, using A549 lung cells. Among the PAHs, chrysene, benzo[a]pyrene (B[a]P), benzo[b]fluoranthene, and benz[a]anthracene showed the highest concentrations (7.8–10 ng/m³), while benzanthrone and 9,10-anthraquinone were the most abundant oxy-PAHs. Testing of PM extracts was based on B[a]P equivalent doses (B[a]Pₑq). IC₅₀ values for viability were 5.7 and 3.0 nM B[a]Pₑq at 24 h and 48 h, respectively. At these low doses, we observed a time- and dose-dependent increase in intracellular levels of ROS, genotoxicity (DNA strand breaks) and DNA damage signaling (phosphorylation of the protein checkpoint kinase 1 – Chk1). In comparison, effects of B[a]P alone was observed at micromolar range. To our knowledge, no previous study has demonstrated an activation of pChk1, a biomarker used to estimate the carcinogenic potency of PAHs in vitro, in lung cells exposed to cashew nut roasting extracts. Sustained induction of expression of several important stress response mediators of xenobiotic metabolism (CYP1A1, CYP1B1), ROS and pro-inflammatory response (IL-8, TNF-α, IL-2, COX2), and DNA damage response (CDKN1A and DDB2) was also identified. In conclusion, our data show high potency of cashew nut roasting PM to induce cellular stress including genotoxicity, and more potently when compared to B[a]P alone. Our study provides new data that will help elucidate the toxic effects of low-levels of PAH mixtures from air PM generated by cashew nut roasting.
显示更多 [+] 显示较少 [-]Biotransformation and tissue bioaccumulation of 8:2 fluorotelomer alcohol in broiler by oral exposure
2020
Chen, Dongmei | Zhao, Ying | Xu, Wei | Pan, Yuanhu | Wei, Qu | Xie, Shuyu
In order to examine whether 8:2 FTOH exposure would lead to a contamination risk of perfluoroalkyl and polyfluoroalkyl substances (PFASs) in broiler derived food, the biotransformation, and tissue distribution and accumulation of 8:2 FTOH following oral exposure in male broilers were investigated. The main metabolites of 8:2 FTOH in plasma and six tissues (muscle, liver, kidney, fat, heart, and lungs) identified by LC-Q-TOF were 2-perfluorooctyl ethanoic acid (8:2 FTCA), 8:2 fluorotelomer unsaturated carboxylic acid (8:2 FTUCA), 3-perfluoroheptyl propanoic acid (7:3 FTCA), perfluoropentanoic acid (PFPeA), perfluorooctanoic acid (PFOA), perfluoroheptanoic acid (PFHpA), perfluorohexanoic acid (PFHxA), perfluorononanoic acid (PFNA), 8:2 FTOH glucuronide conjugate, and 8:2 FTOH sulfate conjugate. The tissue distribution and bioaccumulation of 8:2 FTOH and its unconjugated metabolites were determinated by LC-MS/MS. 8:2 FTOH was quickly depleted in plasma and all six tested tissues, while PFOA, PFNA, and 7:3 FTCA showed strong accumulation in blood and all six examined tissues and were eliminated more slowly than the other metabolites. The tissues with the highest accumulation levels for 8:2 FTOH and its metabolites were heart, kidneys and liver, and the tissue with the lowest accumulation levels was muscle. The elimination half-lifes of PFNA in kidney and 7:3 FTCA in lung were longer compared to those of other metabolites in all six determined tissues. Thus, PFNA and 7:3 FTCA can be selected as potential biomonitoring markers after 8:2 FTOH exposure. This study has improved our understanding of 8:2 FTOH biotransformation and tissue bioaccumulation in broilers, which will help us monitor human exposure risk via food derived from broilers polluted by 8:2 FTOH.
显示更多 [+] 显示较少 [-]How safe are the new green energy resources for marine wildlife? The case of lithium
2020
Viana, Thainara | Ferreira, Nicole | Henriques, Bruno | Leite, Carla | De Marchi, Lucia | Amaral, Joana | Freitas, Rosa | Pereira, Eduarda
Considering the increasing use of Lithium (Li) and the necessity to fulfil this demand, labile Li occurrence in the environment will be enhanced. Thus, additional research is needed regarding the presence of this element in marine environment and its potential toxic impacts towards inhabiting wildlife. The aim of the present study was to evaluate Li toxicity based on the exposure of Mytilus galloprovincialis to this metal, assessing the biochemical changes related with mussels’ metabolism, oxidative stress and neurotoxicity. For this, organisms were exposed to different Li concentrations (100, 250, 750 μg/L) for 28 days. The results obtained clearly demonstrated that Li lead to mussels’ metabolism depression. The present study also revealed that, especially at the highest concentrations, antioxidant and biotransformation enzymes were not activated, leading to the occurrence of lipid peroxidation and loss of redox homeostasis, with increased content in oxidized glutathione in comparison to the reduced form. Furthermore, after 28 days, higher Li exposure concentrations induced neurotoxic effects in mussels, with a decrease in acetylcholinesterase enzyme activity. The responses observed were closely related with Li concentrations in mussels’ tissues, which were more pronounced at higher exposure concentrations. Such results highlight the potential toxic effects of Li to marine species, which may even be higher under predicted climate changes and/or in the presence of other pollutants.
显示更多 [+] 显示较少 [-]Tissue-specific bioaccumulation, metabolism and excretion of tris (2-ethylhexyl) phosphate (TEHP) in rare minnow (Gobiocyprisrarus)
2020
Hou, Rui | Xu, Yiping | Rao, Kaifeng | Feng, Chenglian | Wang, Zijian
Tris (2-ethylhexyl) phosphate (TEHP) is one of the most commonly used organophosphorus flame retardant (OPFR) analogues and is commonly detected in surface water and sediments. Limited information is available about the metabolic pathway or metabolite formation related to TEHP in fish. In this study, rare minnows (Gobiocyprisrarus) were exposed to TEHP in static water for 30 d to investigate the bioaccumulation and metabolite distribution in the fish muscle, liver, kidney, gill, GI-tract, ovary and testis. Based on the estimated kᵤₚ,ₚₐᵣₑₙₜ and kd,ₚₐᵣₑₙₜ values, the bioconcentration factors (BCFₚₐᵣₑₙₜ) of TEHP in fish tissues were calculated in the order of kidney > ovary ≈ liver ≈ testis > gill ≈ GI-tract > muscle; this finding was consistent with the results of our previous study on other alkyl-substituted OPFRs. In addition, this study identified the metabolic profiles of TEHP in the liver. TEHP was oxidatively metabolized by the fish to a dealkylated metabolite (di 2-ethylhexyl phosphate; DEHP) and hydroxylated TEHP (OH-TEHP). OH-TEHP further underwent extensive phase II metabolism to yield glucuronic acid conjugates. DEHP was mainly distributed in rare minnow in the following order: liver > GI-tract > kidney ≫ other tissues. However, the metabolite showed lower accumulation potential in fish tissues than TEHP, with metabolite parent concentration factors (MPCFs) for DEHP of less than 0.1 in all the investigated tissues. The BCFₚₐᵣₑₙₜ values of TEHP in various fish tissues were only 9.0 × 10⁻³-7.2 × 10⁻⁴ times its estimated tissue-water partition coefficient (Kₜᵢₛₛᵤₑ₋wₐₜₑᵣ) values based on tissue lipid, protein and water contents, which indicated the significance of biotransformation in reducing the bioaccumulation potential of TEHP in fish. The toxicokinetic data in the present study help in understanding the tissue-specific bioaccumulation and metabolism pathways of TEHP in fish and highlight the importance of toxicology research on TEHP metabolites in aquatic organisms.
显示更多 [+] 显示较少 [-]The response of arsenic bioavailability and microbial community in paddy soil with the application of sulfur fertilizers
2020
Tang, Xianjin | Li, Luyao | Wu, Chuan | Khan, Muhammed Imran | Manzoor, Maria | Zou, Lina | Shi, Jiyan
Arsenic (As) has been recognized as one of the most toxic metalloids present in the surface soil contaminating food chain and posing threat to human life. Sulfur (S) fertilizer is often supplied in paddy soil for rice growth, but its impact on As mobility and related bacteria remains poorly understood. In this study, a pot experiment was set up with two different types of sulfur treatments (element sulfur and Na₂SO₄) to evaluate the effect of sulfur fertilizers on As speciation in porewater, As fractions in soil, As accumulation in rice plants. Besides, rhizosphere bacterial composition and functional genes that might influence As mobility were also studied. The results revealed that the addition of 150 mg/kg Na₂SO₄ decreased As(III) and As(V) concentrations in soil porewater at maturation stage by 77% and 64%, respectively. With the same sulfur content, Na₂SO₄ was more effective than element sulfur. The addition of sulfur fertilizers promoted rice growth and reduced As accumulation in shoots, further reduced As translocation from root to above-ground parts by 39–59%. The addition of sulfur fertilizers had little effect on genes involved in As metabolism. However, the relative abundance of Fe(III) and sulfate reduction related genera increased with the addition of 150 mg/kg Na₂SO₄, consistent with the increase of Fe(III) reducing bacteria Geobacteraceae and sulfate reducing gene dsrA. The phenomenon likely influenced the decrease of As concentrations in soil porewater and rice uptake. The outcomes indicate that promoting Fe- and S- reducing bacteria in the rhizosphere by sulfur fertilizers may be one way to reduce As risk in the soil-rice system.
显示更多 [+] 显示较少 [-]Anti-inflammatory drugs in the marine environment: Bioconcentration, metabolism and sub-lethal effects in marine bivalves
2020
Almeida, Angela Maria da | Solé, Montserrat | Soares, Amadeu M.V.M. | Freitas, Rosa
Pharmaceuticals such as non-steroidal anti-inflammatory drugs (NSAIDs) have been found in the marine environment. Although there is a large body of evidence that pharmaceutical drugs exert negative impacts on aquatic organisms, especially in the freshwater compartment, only limited studies are available on bioconcentration and the effects of NSAIDs on marine organisms. Bivalves have a high ecological and socio-economic value and are considered good bioindicator species in ecotoxicology and risk assessment programs. Therefore, this review summarizes current knowledge on the bioconcentration and the effects of three widely used NSAIDs, diclofenac, ibuprofen and paracetamol, in marine bivalves exposed under laboratory conditions. These pharmaceutical drugs were chosen based on their environmental occurrence both in frequency and concentration that may warrant their inclusion in the European Union Watch List. It has been highlighted that ambient concentrations may result in negative effects on wild bivalves after long-term exposures. Also, higher trophic level organisms may be more impacted due to food-chain transfer (e.g., humans are shellfish consumers). Overall, the three selected NSAIDs were reported to bioconcentrate in marine bivalves, with recognized effects at different life-stages. Immune responses were the main target of a long-term exposure to the drugs. The studies selected support the inclusion of diclofenac on the European Union Watch List and highlight the importance of extending research for ibuprofen and paracetamol due to their demonstrated negative effects on marine bivalves exposed to environmental realistic concentrations, under laboratory conditions.
显示更多 [+] 显示较少 [-]New insights on the impacts of e-waste towards marine bivalves: The case of the rare earth element Dysprosium
2020
With the technological advances and economic development, the multiplicity and wide variety of applications of electrical and electronic equipment have increased, as well as the amount of end-of-life products (waste of electrical and electronic equipment, WEEE). Accompanying their increasing application, there is an increasing risk to aquatic ecosystems and inhabiting organisms. Among the most common elements present in WEEE are rare earth elements (REE) such as Dysprosium (Dy). The present study evaluated the metabolic and oxidative stress responses of mussels Mytilus galloprovincialis exposed to an increasing range of Dy concentrations, after a 28 days experimental period. The results obtained highlighted that Dy was responsible for mussel’s metabolic increase associated with glycogen expenditure, activation of antioxidant and biotransformation defences and cellular damage, with a clear loss of redox balance. Such effects may greatly impact mussel’s physiological functions, including reproduction capacity and growth, with implications for population conservation. Overall the present study pointed out the need for more research on the toxic impacts resulting from these emerging pollutants, especially towards marine and estuarine invertebrate species.
显示更多 [+] 显示较少 [-]Application of advanced HepG2 3D cell model for studying genotoxic activity of cyanobacterial toxin cylindrospermopsin
2020
Hercog, Klara | Štampar, Martina | Štern, Alja | Filipič, Metka | Žegura, Bojana
Cylindrospermopsin (CYN) is an emerging cyanotoxin increasingly being found in freshwater cyanobacterial blooms worldwide. Humans and animals are exposed to CYN through the consumption of contaminated water and food as well as occupational and recreational water activities; therefore, it represents a potential health threat. It exhibits genotoxic effects in metabolically active test systems, thus it is considered as pro-genotoxic. In the present study, the advanced 3D cell model developed from human hepatocellular carcinoma (HepG2) cells was used for the evaluation of CYN cyto-/genotoxic activity. Spheroids were formed by forced floating method and were cultured for three days under static conditions prior to exposure to CYN (0.125, 0.25 and 0.5 μg/mL) for 72 h. CYN influence on spheroid growth was measured daily and cell survival was determined by MTS assay and live/dead staining. The influence on cell proliferation, cell cycle alterations and induction of DNA damage (γH2AX) was determined using flow cytometry. Further, the expression of selected genes (qPCR) involved in the metabolism of xenobiotics, proliferation, DNA damage response, apoptosis and oxidative stress was studied. Results revealed that CYN dose-dependently reduced the size of spheroids and affected cell division by arresting HepG2 cells in G1 phase of the cell cycle. No induction of DNA double strand breaks compared to control was determined at applied conditions. The analysis of gene expression revealed that CYN significantly deregulated genes encoding phase I (CYP1A1, CYP1A2, CYP3A4, ALDH3A) and II (NAT1, NAT2, SULT1B1, SULT1C2, UGT1A1, UGT2B7) enzymes as well as genes involved in cell proliferation (PCNA, TOP2α), apoptosis (BBC3) and DNA damage response (GADD45a, CDKN1A, ERCC4). The advanced 3D HepG2 cell model due to its more complex structure and improved cellular interactions provides more physiologically relevant information and more predictive data for human exposure, and can thus contribute to more reliable genotoxicity assessment of chemicals including cyanotoxins.
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