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Ractopamine at legal residue dosage accelerates atherosclerosis by inducing endothelial dysfunction and promoting macrophage foam cell formation Full text
2022
Chen, Chia-Hui | Guo, Bei-Chia | Hu, Po-An | Lee, Hsueh-Te | Hu, Hsuan-Yun | Hsu, Man-Chen | Chen, Wen-Hua | Lee, Tzong-Shyuan
Ractopamine, a synthetic β-adrenoreceptor agonist, is used as an animal feed additive to increase food conversion efficiency and accelerate lean mass accretion in farmed animals. The U.S. Food and Drug Administration claimed that ingesting products containing ractopamine residues at legal dosages might not cause short-term harm to human health. However, the effect of ractopamine on chronic inflammatory diseases and atherosclerosis is unclear. Therefore, we investigated the effects of ractopamine on atherosclerosis and its action mechanism in apolipoprotein E-null (apoe⁻/⁻) mice and human endothelial cells (ECs) and macrophages. Daily treatment with ractopamine for four weeks increased the body weight and the weight of brown adipose tissues and gastrocnemius muscles. However, it decreased the weight of white adipose tissues in apoe⁻/⁻ mice. Additionally, ractopamine exacerbated hyperlipidemia and systemic inflammation, deregulated aortic cholesterol metabolism and inflammation, and accelerated atherosclerosis. In ECs, ractopamine treatment induced endothelial dysfunction and increased monocyte adhesion and transmigration across ECs. In macrophages, ractopamine dysregulated cholesterol metabolism by increasing oxidized low-density lipoprotein (oxLDL) internalization and decreasing reverse cholesterol transporters, increasing oxLDL-induced lipid accumulation. Collectively, our findings revealed that ractopamine induces EC dysfunction and deregulated cholesterol metabolism of macrophages, which ultimately accelerates atherosclerosis progression.
Show more [+] Less [-]Spatio-temporal patterns of occurrence of microplastics in the freshwater fish Gambusia affinis from the Brantas River, Indonesia Full text
2022
Buwono, Nanik Retno | Risjani, Yenny | Soegianto, Agoes
The first investigation of microplastics in G. affinis from the Brantas River was carried out in this study. Microplastics were found at higher concentrations in gambusia fish captured downstream (209.18 ± 48.85 particles/gram) than upstream (24.44 ± 0.14 particles/gram). Microplastic particle concentrations in G. affinis have a positive linear relationship with fish length. The fiber was the most prominent shape at Sites 1 and 2, whereas the fragment was dominant at Sites 3 and 4. With a value of 45–48%, black dominates the entire site, followed by blue (29–38%), transparent colors (7–11%), red (2–4%), purple (1–3%), and other colors (5–7%). Microplastics measuring <0.1 mm are commonly found in fish bodies. Cyclohexylmethyl octyl ester (phthalic acid) is the most abundant component found in microplastics, accounting for 30.11% of the total. This study provides evidence that G. affinis can be used to monitor the presence of microplastic pollution in the Brantas River but further studies are needed regarding the effects of microplastics and their health hazards on fish.
Show more [+] Less [-]Development of physiologically-based toxicokinetic-toxicodynamic (PBTK-TD) model for 4-nonylphenol (4-NP) reflecting physiological changes according to age in males: Application as a new risk assessment tool with a focus on toxicodynamics Full text
2022
Jeong, Seung-Hyun | Jang, Ji-Hun | Lee, Yong-Bok
Environmental exposure to 4-nonylphenol (4-NP) is extensive, and studies related to human risk assessment must continue. Especially, prediction of toxicodynamics (TDs) related to reproductive toxicity in males is very important in risk-level assessment and management of 4-NP. This study aimed to develop a physiologically-based-toxicokinetic-toxicodynamic (PBTK-TD) model that added a TD prostate model to the previously reported 4-n-nonylphenol (4-n-NP) physiologically-based-pharmacokinetic (PBPK) model. Modeling was performed under the assumption of similar TKs between 4-n-NP and 4-NP because TK experiments on 4-NP, a random-mixture, are practically difficult. This study was very important to quantitatively predict the TKs and TDs of 4-NP by age at exposure using an advanced PBTK-TD model that reflected physiological-changes according to age. TD-modeling was performed based on the reported toxic effects of 4-NP on RWPE-1 cells, a human-prostate-epithelial-cell-line. Through a meta-analysis of reported human physiological data, body weight, tissue volume, and blood flow rate patterns according to age were mathematically modeled. These relationships were reflected in the PBTK-TD model for 4-NP so that the 4-NP TK and TD changes according to age and their differences could be confirmed. Differences in TK and TD parameters of 4-NP at various ages were not large, within 3.61-fold. Point-of-departure (POD) and reference-doses for each age estimated using the model varied as 426.37–795.24 and 42.64–79.52 μg/kg/day, but the differences (in POD or reference doses between ages) were not large, at less than 1.87-times. The PBTK-TD model simulation predicted that even a 100-fold 4-NP PODₘₐₙ dose would not have large toxicity to the prostate. With a focus on TDs, the predicted maximum possible exposure of 4-NP was as high as 6.06–23.60 mg/kg/day. Several toxicity-related values estimated by the dose-response curve were higher than those calculated, depending upon the PK or TK, which would be useful as a new exposure limit for prostate toxicity of 4-NP.
Show more [+] Less [-]Effects of life cycle exposure to polystyrene microplastics on medaka fish (Oryzias latipes) Full text
2022
González-Doncel, Miguel | García-Mauriño, José Enrique | Beltrán, Eulalia María | Fernández Torija, Carlos | Andreu-Sánchez, Oscar | Pablos, María Victoria
Effects of life cycle exposure to polystyrene microplastics on medaka fish (Oryzias latipes) Full text
2022
González-Doncel, Miguel | García-Mauriño, José Enrique | Beltrán, Eulalia María | Fernández Torija, Carlos | Andreu-Sánchez, Oscar | Pablos, María Victoria
The number of published studies evaluating the effects of microplastics (MPs) in fish has increased in the last decade. However, of the available studies, few have explored the long-term effects of MPs on fish growth and reproduction and have resorted to MPs in the form of μm-sized beads/microspheres. In this study, 6-10 day-old post-hatch medaka (Oryzias latipes) fish were exposed to 50 (i.e. 1X) and 500 (i.e. 10X) μg of heterogeneously sized and irregularly shaped virgin polystyrene (PS) MP particles (200-μm range)/L for 150 days. These concentrations corresponded to respective daily mean values of 247 and 3087 particles/L administered through the diet. The PS MPs dietary exposure resulted in body burdens of 114 and 440 particles/g fish on day 50, and of 78 and 173 particles/g fish on day 100 since the respective exposures to the 1X and the 10X treatments started. The biometric analyses found no incidence of PS MPs ingestion on overall fish growth and development. The histological survey in the 10X group did not reveal alterations in gills or in the digestive tract. Mild alterations in other organs were seen and included increased fluid material in the peritoneal cavity, glomerular and tubular alterations in kidneys, and differences in the diameter of the thyroid follicles and thickness of the follicular epithelial cells. The initial days of the reproductive phase revealed MP-related differences in the number of gravid females, fecundity, and fertilization rates. Overall, these values reverted to normal rates throughout the succeeding days. No significant effects of PS MPs exposure were evidenced on offspring success. The 150-day PS MPs dietary exposure used in this study provided clues of histological effects and a reproduction delay. However, it did not seem to compromise overall growth/thriving and the ongoing reproduction.
Show more [+] Less [-]Effects of life cycle exposure to polystyrene microplastics on medaka fish (Oryzias latipes) Full text
2022
Gonzalez-Doncel, M. | García-Mauriño, J. E. | María Beltrán, E. | Fernández Torija, C. | Andreu-Sánchez, Oscar | Pablos Chi, M. V.
The number of published studies evaluating the effects of microplastics (MPs) in fish has increased in the last decade. However, of the available studies, few have explored the long-term effects of MPs on fish growth and reproduction and have resorted to MPs in the form of μm-sized beads/microspheres. In this study, 6-10 day-old post-hatch medaka (Oryzias latipes) fish were exposed to 50 (i.e. 1X) and 500 (i.e. 10X) μg of heterogeneously sized and irregularly shaped virgin polystyrene (PS) MP particles (200-μm range)/L for 150 days. These concentrations corresponded to respective daily mean values of 247 and 3087 particles/L administered through the diet. The PS MPs dietary exposure resulted in body burdens of 114 and 440 particles/g fish on day 50, and of 78 and 173 particles/g fish on day 100 since the respective exposures to the 1X and the 10X treatments started. The biometric analyses found no incidence of PS MPs ingestion on overall fish growth and development. The histological survey in the 10X group did not reveal alterations in gills or in the digestive tract. Mild alterations in other organs were seen and included increased fluid material in the peritoneal cavity, glomerular and tubular alterations in kidneys, and differences in the diameter of the thyroid follicles and thickness of the follicular epithelial cells. The initial days of the reproductive phase revealed MP-related differences in the number of gravid females, fecundity, and fertilization rates. Overall, these values reverted to normal rates throughout the succeeding days. No significant effects of PS MPs exposure were evidenced on offspring success. The 150-day PS MPs dietary exposure used in this study provided clues of histological effects and a reproduction delay. However, it did not seem to compromise overall growth/thriving and the ongoing reproduction.
Show more [+] Less [-]Effects of life cycle exposure to polystyrene microplastics on medaka fish (Oryzias latipes) Full text
2022
The number of published studies evaluating the effects of microplastics (MPs) in fish has increased in the last decade. However, of the available studies, few have explored the long-term effects of MPs on fish growth and reproduction and have resorted to MPs in the form of μm-sized beads/microspheres. In this study, 6-10 day-old post-hatch medaka (Oryzias latipes) fish were exposed to 50 (i.e. 1X) and 500 (i.e. 10X) μg of heterogeneously sized and irregularly shaped virgin polystyrene (PS) MP particles (200-μm range)/L for 150 days. These concentrations corresponded to respective daily mean values of 247 and 3087 particles/L administered through the diet. The PS MPs dietary exposure resulted in body burdens of 114 and 440 particles/g fish on day 50, and of 78 and 173 particles/g fish on day 100 since the respective exposures to the 1X and the 10X treatments started. The biometric analyses found no incidence of PS MPs ingestion on overall fish growth and development. The histological survey in the 10X group did not reveal alterations in gills or in the digestive tract. Mild alterations in other organs were seen and included increased fluid material in the peritoneal cavity, glomerular and tubular alterations in kidneys, and differences in the diameter of the thyroid follicles and thickness of the follicular epithelial cells. The initial days of the reproductive phase revealed MP-related differences in the number of gravid females, fecundity, and fertilization rates. Overall, these values reverted to normal rates throughout the succeeding days. No significant effects of PS MPs exposure were evidenced on offspring success. The 150-day PS MPs dietary exposure used in this study provided clues of histological effects and a reproduction delay. However, it did not seem to compromise overall growth/thriving and the ongoing reproduction.
Show more [+] Less [-]Field mixtures of currently used pesticides in agricultural soil pose a risk to soil invertebrates Full text
2022
Panico, Speranza C. | van Gestel, Cornelis A.M. | Verweij, Rudo A. | Rault, Magali | Bertrand, Colette | Menacho Barriga, Carlos A. | Coeurdassier, Michaël | Fritsch, Clémentine | Gimbert, Frédéric | Pelosi, Céline
Field mixtures of currently used pesticides in agricultural soil pose a risk to soil invertebrates Full text
2022
Panico, Speranza C. | van Gestel, Cornelis A.M. | Verweij, Rudo A. | Rault, Magali | Bertrand, Colette | Menacho Barriga, Carlos A. | Coeurdassier, Michaël | Fritsch, Clémentine | Gimbert, Frédéric | Pelosi, Céline
Massive use of pesticides in conventional agriculture leads to accumulation in soil of complex mixtures, triggering questions about their potential ecotoxicological risk. This study assessed cropland soils containing pesticide mixtures sampled from conventional and organic farming systems at La Cage and Mons, France. The conventional agricultural field soils contained more pesticide residues (11 and 17 versus 3 and 11, respectively) and at higher concentrations than soils from organic fields (mean 6.6 and 10.5 versus 0.2 and 0.6 μg kg⁻¹, respectively), including systemic insecticides belonging to neonicotinoids, carbamate herbicides and broad-spectrum fungicides mostly from the azole family. A risk quotient (RQᵢ) approach evaluated the toxicity of the pesticide mixtures in soil, assuming concentration addition. Based on measured concentrations, both conventional agricultural soils posed high risks to soil invertebrates, especially due to the presence of epoxiconazole and imidacloprid, whereas soils under organic farming showed negligible to medium risk. To confirm the outcome of the risk assessment, toxicity of the soils was determined in bioassays following standardized test guidelines with seven representative non-target invertebrates: earthworms (Eisenia andrei, Lumbricus rubellus, Aporrectodea caliginosa), enchytraeids (Enchytraeus crypticus), Collembola (Folsomia candida), oribatid mites (Oppia nitens), and snails (Cantareus aspersus). Collembola and enchytraeid survival and reproduction and land snail growth were significantly lower in soils from conventional compared to organic agriculture. The earthworms displayed different responses: L. rubellus showed higher mortality on soils from conventional agriculture and large body mass loss in all field soils, E. andrei showed considerable mass loss and strongly reduced reproduction, and A. caliginosa showed significantly reduced acetylcholinesterase activity in soils from conventional agriculture. The oribatid mites did not show consistent differences between organic and conventional farming soils. These results highlight that conventional agricultural practices pose a high risk for soil invertebrates and may threaten soil functionality, likely due to additive or synergistic “cocktail effects”.
Show more [+] Less [-]Field mixtures of currently used pesticides in agricultural soil pose a risk to soil invertebrates Full text
2022
Panico, Speranza, C | van Gestel, Cornelis, a M | Verweij, Rudo, A | Rault, Magali | Bertrand, Colette | Menacho Barriga, Carlos, A | Coeurdassier, Michaël | Fritsch, Clémentine | Gimbert, Frédéric | Pélosi, Céline | Vrije Universiteit Brussel (VUB) | University of Naples Federico II = Università degli studi di Napoli Federico II | Institut méditerranéen de biodiversité et d'écologie marine et continentale (IMBE) ; Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement [IRD] : UMR237-Centre National de la Recherche Scientifique (CNRS) | Ecologie fonctionnelle et écotoxicologie des agroécosystèmes (ECOSYS) ; AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Laboratoire Chrono-environnement (UMR 6249) (LCE) ; Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC) ; Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC) | Environnement Méditerranéen et Modélisation des Agro-Hydrosystèmes (EMMAH) ; Avignon Université (AU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | This study was performed within the framework of the “PING” research project, funded by the M´etaprogramme INRAe SMaCH Call2017. The study also benefited from results obtained during the “RESCAPE” research project, action led by the Ministry for Agricultureand Food and the Ministry for an Ecological and Solidary Transition, with the financial support of the French Biodiversity Agency on“Resistance and Pesticides” research call, with the fees for diffuse pollution coming from the Ecophyto Plan through the national agencyONEMA.
International audience | Massive use of pesticides in conventional agriculture leads to accumulation in soil of complex mixtures, triggering questions about their potential ecotoxicological risk. This study assessed cropland soils containing pesticide mixtures sampled from conventional and organic farming systems at La Cage and Mons, France. The conventional agricultural field soils contained more pesticide residues (11 and 17 versus 3 and 11, respectively) and at higher concentrations than soils from organic fields (mean 6.6 and 10.5 versus 0.2 and 0.6 μg kg − 1 , respectively), including systemic insecticides belonging to neonicotinoids, carbamate herbicides and broadspectrum fungicides mostly from the azole family. A risk quotient (RQ i) approach evaluated the toxicity of the pesticide mixtures in soil, assuming concentration addition. Based on measured concentrations, both conventional agricultural soils posed high risks to soil invertebrates, especially due to the presence of epoxiconazole and imidacloprid, whereas soils under organic farming showed negligible to medium risk. To confirm the outcome of the risk assessment, toxicity of the soils was determined in bioassays following standardized test guidelines with seven representative non-target invertebrates: earthworms (Eisenia andrei, Lumbricus rubellus, Aporrectodea caliginosa), enchytraeids (Enchytraeus crypticus), Collembola (Folsomia candida), oribatid mites (Oppia nitens), and snails (Cantareus aspersus). Collembola and enchytraeid survival and reproduction and land snail growth were significantly lower in soils from conventional compared to organic agriculture. The earthworms displayed different responses: L. rubellus showed higher mortality on soils from conventional agriculture and large body mass loss in all field soils, E. andrei showed considerable mass loss and strongly reduced reproduction, and A. caliginosa showed significantly reduced acetylcholinesterase activity in soils from conventional agriculture. The oribatid mites did not show consistent differences between organic and conventional farming soils. These results highlight that conventional agricultural practices pose a high risk for soil invertebrates and may threaten soil functionality, likely due to additive or synergistic "cocktail effects". ☆ This paper has been recommended for acceptance by Montes Marques.
Show more [+] Less [-]Field mixtures of currently used pesticides in agricultural soil pose a risk to soil invertebrates Full text
2022
Panico, Speranza, C | van Gestel, Cornelis, a M | Verweij, Rudo, A | Rault, Magali | Bertrand, Colette | Menacho Barriga, Carlos, A | Coeurdassier, Michaël | Fritsch, Clémentine | Gimbert, Frédéric | Pélosi, Céline | Vrije Universiteit Brussel [Bruxelles] (VUB) | University of Naples Federico II = Università degli studi di Napoli Federico II | Institut méditerranéen de biodiversité et d'écologie marine et continentale (IMBE) ; Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement [IRD] : UMR237-Centre National de la Recherche Scientifique (CNRS) | Ecologie fonctionnelle et écotoxicologie des agroécosystèmes (ECOSYS) ; AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Laboratoire Chrono-environnement (UMR 6249) (LCE) ; Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC) ; Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC) | Environnement Méditerranéen et Modélisation des Agro-Hydrosystèmes (EMMAH) ; Avignon Université (AU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | This study was performed within the framework of the “PING” research project, funded by the M´etaprogramme INRAe SMaCH Call2017. The study also benefited from results obtained during the “RESCAPE” research project, action led by the Ministry for Agricultureand Food and the Ministry for an Ecological and Solidary Transition, with the financial support of the French Biodiversity Agency on“Resistance and Pesticides” research call, with the fees for diffuse pollution coming from the Ecophyto Plan through the national agencyONEMA.
International audience | Massive use of pesticides in conventional agriculture leads to accumulation in soil of complex mixtures, triggering questions about their potential ecotoxicological risk. This study assessed cropland soils containing pesticide mixtures sampled from conventional and organic farming systems at La Cage and Mons, France. The conventional agricultural field soils contained more pesticide residues (11 and 17 versus 3 and 11, respectively) and at higher concentrations than soils from organic fields (mean 6.6 and 10.5 versus 0.2 and 0.6 μg kg − 1 , respectively), including systemic insecticides belonging to neonicotinoids, carbamate herbicides and broadspectrum fungicides mostly from the azole family. A risk quotient (RQ i) approach evaluated the toxicity of the pesticide mixtures in soil, assuming concentration addition. Based on measured concentrations, both conventional agricultural soils posed high risks to soil invertebrates, especially due to the presence of epoxiconazole and imidacloprid, whereas soils under organic farming showed negligible to medium risk. To confirm the outcome of the risk assessment, toxicity of the soils was determined in bioassays following standardized test guidelines with seven representative non-target invertebrates: earthworms (Eisenia andrei, Lumbricus rubellus, Aporrectodea caliginosa), enchytraeids (Enchytraeus crypticus), Collembola (Folsomia candida), oribatid mites (Oppia nitens), and snails (Cantareus aspersus). Collembola and enchytraeid survival and reproduction and land snail growth were significantly lower in soils from conventional compared to organic agriculture. The earthworms displayed different responses: L. rubellus showed higher mortality on soils from conventional agriculture and large body mass loss in all field soils, E. andrei showed considerable mass loss and strongly reduced reproduction, and A. caliginosa showed significantly reduced acetylcholinesterase activity in soils from conventional agriculture. The oribatid mites did not show consistent differences between organic and conventional farming soils. These results highlight that conventional agricultural practices pose a high risk for soil invertebrates and may threaten soil functionality, likely due to additive or synergistic "cocktail effects". ☆ This paper has been recommended for acceptance by Montes Marques.
Show more [+] Less [-]MiR-34a/Sirt1/p53 signaling pathway contributes to cadmium-induced nephrotoxicity: A preclinical study in mice Full text
2021
Hao, Rili | Song, Xinyu | Sun-Waterhouse, Dongxiao | Tan, Xintong | Li, Feng | Li, Dapeng
Cadmium (Cd), as an environmental pollutant, can lead to nephrotoxicity. However, its nephrotoxicological mechanisms have not been fully elucidated. In this study, Cd (1.5 mg/kg body weight, gavaged for 4 weeks) was found to induce the renal damage in mice, based on indicators including Cd concentration, kidney index, serum creatinine and blood urea nitrogen levels, pro-inflammatory cytokines and their mRNA expressions, levels of Bcl-2, Bax and caspase9, and histopathological changes of the kidneys. Furthermore, Cd-caused detrimental changes through inducing inflammation and apoptosis via the miR-34a/Sirt1/p53 axis. This is the first report on the role of miR-34a/Sirt1/p53 axis in regulating Cd-caused apoptosis and nephrotoxicity in mice. The findings obtained in this study provide new insights into miRNA-based regulation of heavy metal induced-nephrotoxicity.
Show more [+] Less [-]Tannic acid repair of zearalenone-induced damage by regulating the death receptor and mitochondrial apoptosis signaling pathway in mice Full text
2021
Wu, Jing | Li, Jiayan | Liu, Yanwei | Liao, Xinxin | Wu, Dongyi | Chen, Yunqin | Liang, Zengenni | Yuan, Zhihang | Li, Rongfang | Yi, Jine | Wen, Lixin
Zearalenone (ZEA) is an estrogenic toxin produced by Fusarium strains, that is widely present in crops, and endangers the reproductive system of animals. Tannic acid (TA) is a natural polyphenolic substance that is widespread in the roots, stems, and leaves of plants, and has special pharmacological activity. This study was designed to investigate the therapeutic effect of TA on ZEA-induced ovarian damage in mice and to explore the molecular mechanism involved. Ninety healthy Kunming female mice were divided into six equal groups. All the groups but the control group were administered daily with ZEA [10 mg/kg body weight (bw)] orally, for 7 days, to induce damage to the reproductive system. Some groups were also administered with TA (50, 100, and 200 mg/bw) for 7 days. Mice were euthanized 24 h later to allow for collection of serum and ovaries. TA can effectively alleviate the appearance of congestion and redness of the ovary, caused by ZEA, and increase the number of healthy growing follicles. Moreover, the estrogen content and the levels of MDA and ROS in the ovaries can be effectively reduced by TA. It can also reduce the apoptosis of ovarian cells, decreases the protein expression of the estrogen receptor, Fas, Fasl, caspase-3, caspase-8, caspase-9, and Bax, and increases the protein expression of Bcl-2. Our study indicates that TA reduces the strong estrogen and oxidative damage induced by ZEA, and these therapeutic effects may be partially mediated by the death receptor and mitochondrial apoptosis signaling pathway.
Show more [+] Less [-]The role of Nrf2 in mitigating cadmium-induced oxidative stress of Marsupenaeus japonicus Full text
2021
Ren, Xianyun | Xu, Yao | Yu, Zhenxing | Mu, Cuimin | Liu, Ping | Li, Jian
Nuclear factor-erythroid 2-related factor-2 (Nrf2) is an important modulator of cellular responses against Cd in mammalian cells. However, whether such modulation is conserved in Marsupenaeus japonicas remains unknown.In our study, the shrimps were injected with dsRNA targeting Nrf2 at 4 μg g⁻¹ body weight (b.w.) or sulforaphane (SFN) at 5 μg g⁻¹ b.w., and then were exposed to 40 mg L⁻¹ CdCl₂ for 48 h. After Nrf2 knockdown, the Cd content increased, but decreased in the SFN group. This suggested that Nrf2 could promote Cd excretion. A terminal deoxynulceotidyl transferase nick-end-labeling (TUNEL) assay revealed that the Nrf2 knockdown increased the number of apoptotic cells in M. japonicas, while SFN decreased the number of apoptotic cells. After Nrf2 knockdown, the total antioxidant capacity (T-AOC), superoxide dismutase (Sod) activity, and related gene expression decreased significantly, while the malondialdehyde (MDA) content increased remarkably. By contrast, SFN injection alleviated the oxidative stress, as evidenced by increased T-AOC, Sod activity, sod mRNA expression and a reduced MDA content. Similarly, detoxification related enzyme activities (ethoxyresorufin O-deethylase and glutathione-S-transferase (GST)) and their corresponding gene expressions (cyp3a (cytochrome P450 family 3 subfamily A) and gst) were suppressed in the ds-Nrf2 injection group, while they were elevated in the SFN group. In addition, ds-Nrf2 activated mitochondrial apoptotic pathway, as evidenced the mRNA and protein levels of caspase-3, Bcl2 associated X protein (Bax), and p53, while SFN treatment suppressed them. These results displayed that in M. japonicus Cd-induced cellular oxidative damage probably acts via the Nrf2 pathway.
Show more [+] Less [-]Chronic toxicity of waterborne thallium to Daphnia magna Full text
2021
Nagel, Andrew H. | Cuss, Chad W. | Goss, Greg G. | Shotyk, William | Glover, Chris N.
There is limited information regarding the toxicity of the trace element thallium (Tl) to aquatic biota, most of which assesses acute toxicity and bioaccumulation. The relative lack of chronic Tl toxicity data compromises the establishment of water quality criteria for this trace metal. In the presented work, chronic toxicity endpoints (final body weight (a proxy measure of growth), survival, and reproduction) and Tl body burden were measured in the freshwater crustacean Daphnia magna during a 21-day exposure to dissolved Tl. Thallium caused complete mortality in daphnids between exposure concentrations of 424 and 702 μg L⁻¹. In contrast with previously published work examining acute Tl toxicity, exposure to Tl for 21 days was not associated with changes in whole-body potassium concentration. This was despite a 710-fold increase in Tl body burden in animals exposed to 424 μg L⁻¹ relative to the control. Median effect concentrations (EC₅₀’s) for growth and reproduction (total neonates produced), were 1.6 (95% confidence interval: 1.0–3.1) and 11.1 (95% confidence interval: 5.5–21.8) μg Tl L⁻¹, respectively. A no observable effect concentration (NOEC) of 0.9 μg Tl L⁻¹ for growth, and a NOEC range of 0.9–83 μg Tl L⁻¹ for a variety of reproductive metrics, was measured. A lowest observable effect concentration (LOEC) of 8.8 μg Tl L⁻¹ was determined for the effects of Tl on growth and most of the reproductive endpoints examined. These data indicate that under controlled laboratory conditions D. magna is significantly less sensitive to Tl than the species on which the current Canadian Council of Ministers of the Environment regulatory guideline value of 0.8 μg L⁻¹ is based.
Show more [+] Less [-]The protection of selenium against cadmium-induced mitophagy via modulating nuclear xenobiotic receptors response and oxidative stress in the liver of rabbits Full text
2021
Zhang, Linwei | Yang, Fan | Li, Yong | Cao, Huabin | Huang, Aimin | Zhuang, Yu | Zhang, Caiying | Hu, Guoliang | Mao, Yaqing | Luo, Junrong | Xing, Chenghong
Cadmium (Cd) is a harmful heavy metal that can cause many health problems, while selenium (Se) is an essential nutrient for organisms that can protect them from heavy metal-induced damage. To explore the effects of Se on Cd-induced mitophagy in the liver, forty 3-month-old New Zealand white rabbits (2–2.5 kg), half male and half female, were randomly divided into four groups: the Control group, the Se (0.5 mg/kg body weight (BW)) group, the Cd (1 mg/kg BW) group and the Se+Cd group. After 30 days, the toxicity from Cd in the liver was assessed in terms of the nuclear xenobiotic receptor (NXR) response, oxidative stress and mitophagy. It was found that Cd decreased the activities of CYP450 enzymes and antioxidant enzymes and increased the contents of malondialdehyde (MDA) and hydrogen peroxide (H₂O₂) and also increased the consumption of reduced glutathione (GSH). Moreover, the mRNA levels of NXRs (CAR, PXR, AHR and Nrf2), some mitochondrial function factors (PGC-1α, Sirt1, Sirt3, Nrf1 and TFAM) and mitochondrial fusion factors (Mfn1, Mfn2 and OPA1) were downregulated, but the mRNA levels of other mitochondrial function factors (VDAC1, Cyt C and PRDX3), mitochondrial fission factors (Fis1 and MFF) and those in the PINK1/Parkin-mediated mitophagy pathway (p62, Bnip3 and LC3) were upregulated under Cd exposure. The protein expression levels of Nrf2, SOD2, PGC-1α, PINK1 and Parkin were consistent with the mRNA expression levels in the Cd group. Se alleviated the changes in the abovementioned factors induced by Cd. In conclusion, the results indicate that Cd can cause oxidative stress in rabbit livers by inhibiting NXRs and the antioxidation response leading to mitophagy, and these harmful changes caused by Cd can be alleviated by Se.
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