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1.
Molecules ; 29(9)2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38731512

ABSTRACT

Bioremediation uses the degradation abilities of microorganisms and other organisms to remove harmful pollutants that pollute the natural environment, helping return it to a natural state that is free of harmful substances. Organism-derived enzymes can degrade and eliminate a variety of pollutants and transform them into non-toxic forms; as such, they are expected to be used in bioremediation. However, since enzymes are proteins, the low operational stability and catalytic efficiency of free enzyme-based degradation systems need improvement. Enzyme immobilization methods are often used to overcome these challenges. Several enzyme immobilization methods have been applied to improve operational stability and reduce remediation costs. Herein, we review recent advancements in immobilized enzymes for bioremediation and summarize the methods for preparing immobilized enzymes for use as catalysts and in pollutant degradation systems. Additionally, the advantages, limitations, and future perspectives of immobilized enzymes in bioremediation are discussed.


Subject(s)
Biodegradation, Environmental , Environmental Pollutants , Enzymes, Immobilized , Enzymes, Immobilized/chemistry , Enzymes, Immobilized/metabolism , Environmental Pollutants/metabolism , Environmental Pollutants/chemistry , Bioreactors , Hazardous Substances/metabolism
2.
Environ Sci Pollut Res Int ; 31(12): 18340-18361, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38349491

ABSTRACT

Cadmium (Cd) is a naturally occurring environmental pollutant, a toxic substance that causes oxidative stress. According to epidemiological studies, the data suggested that environmental and occupational Cd exposure may be related to several diseases and severe testicular damage. However, studies are going on to explore the mechanism of Cd-induced male reproductive toxicity and its treatment strategies. Currently, researchers are focusing on naturally occurring bioactive compounds, plant extracts, and biochemical, which have better efficacy, less toxicity, and high bioavailability. This review focuses on the mechanistic effect of Cd on testicular toxicity and different categories of compounds having a beneficial impact on Cd-induced male reproductive toxicity. Some potent bioactive antioxidants are quercetin, caffeic acid phenethyl ester, cyanidin-3-O-glucoside, curcumin, and silymarin. In comparison, plant extracts are Costus afer leaf methanol extract, methanol root extract of Carpolobia lutea, red carrot methanolic extract, Panax ginseng extract, and biochemicals including melatonin, progesterone, glutamine, L-carnitine, and selenium. Advanced and more detailed studies are needed on these compounds to explore their mechanism in attenuating Cd-induced testicular toxicity and can be potential therapeutics in the future.


Subject(s)
Cadmium Poisoning , Cadmium , Male , Humans , Cadmium/metabolism , Methanol , Testis , Antioxidants/metabolism , Oxidative Stress , Hazardous Substances/metabolism , Plant Extracts/pharmacology
3.
Environ Sci Pollut Res Int ; 30(11): 28759-28779, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36401692

ABSTRACT

Malachite green (C52H54N4O12) is a synthetic dye that is used in textile industries as a colorant and in aquaculture sectors to contain microbial damage. Aquatic contamination of malachite green (MG) has been reported globally. Fish is the highest trophic organism among aquatic inhabitants, highly sensitive to waterborne contaminants (metals, coloring agents, etc.). Toxicity of waterborne chemicals on nontarget organisms can be determined by assessing biomarkers. Assessing blood parameters and tissue antioxidants (enzymatic and nonenzymatic) is useful to evaluate MG toxicity. To initiate the MG toxicity data for freshwater fish (Cyprinus carpio), the median lethal toxicity was primarily evaluated. Then, hematological, blood biochemical (glucose, protein, and cholesterol) and tissue biochemical (amino acids, lipids), and vital tissue (gills, liver, and kidney) antioxidant capacity (CAT, LPO, GST, GR, POxy, vitamin C, and GSH) of C. carpio were analyzed under acute (LC50-96 h) and sublethal (Treatment I-1/10th and Treatment II-1/5th LC50-96 h) exposure periods (28 days). Molecular docking for MG with hemoglobin was also obtained. Biomarkers examined were affected in the MG-treated groups with respect to the control group. Significant changes (p < 0.05) were observed in hematology (Hb, RBCs, and WBCs), glucose, proteins, lipids and tissue CAT, LPO, and GST activities under acute MG exposure. In sublethal treatment groups, biomarkers studied were significant (p < 0.05) throughout the study period. The potential for MG binding to hemoglobin was tested in this study. MG is potentially a multiorgan toxicant. Literally a chemical that is harmful to the aquatic environment if safety is concerned.


Subject(s)
Carps , Hematology , Water Pollutants, Chemical , Animals , Antioxidants/metabolism , Molecular Docking Simulation , Hazardous Substances/metabolism , Carps/metabolism , Hemoglobins/metabolism , Coloring Agents/metabolism , Glucose/metabolism , Fresh Water/chemistry , Biomarkers/metabolism , Lipids , Water Pollutants, Chemical/toxicity , Water Pollutants, Chemical/metabolism , Gills/metabolism , Oxidative Stress , Liver/metabolism
4.
Theranostics ; 12(15): 6646-6664, 2022.
Article in English | MEDLINE | ID: mdl-36185606

ABSTRACT

Rationale: Active removal of excess peripheral amyloid-ß (Aß) can potentially treat Alzheimer's disease (AD). However, the peripheral clearance of Aß using an anti-Aß monoclonal antibody (mAb) cannot remove PET-detectable Aß within the brain. This may be due to the inability of mAb to cross the blood-brain barrier (BBB) to degrade insoluble brain Aß plaques and block liver dysfunction. Methods: We developed a dual-targeted magnetic mesoporous silica nanoparticle (HA-MMSN-1F12) through surface-coupled Aß42-targeting antibody 1F12 and CD44-targeting ligand hyaluronic acid (HA). Results: HA-MMSN-1F12 had a high binding affinity toward Aß42 oligomers (Kd = 1.27 ± 0.34 nM) and revealed robust degradation of Aß42 aggregates. After intravenous administration of HA-MMSN-1F12 into ten-month-old APP/PS1 mice for three weeks (4 mg/kg/week), HA-MMSN-1F12 could cross the BBB and depolymerize brain Aß plaques into soluble Aß species. In addition, it also avoided hepatic uptake and excreted captured Aß species through intestinal metabolism, thereby reducing brain Aß load and neuroinflammation and improving memory deficits of APP/PS1 mice. Furthermore, the biochemical analysis showed that HA-MMSN-1F12 did not detect any toxic side effects on the liver and kidney. Thus, the efficacy of HA-MMSN-1F12 is associated with the targeted degradation of insoluble brain Aß plaques, avoidance of non-specific hepatic uptake, and excretion of peripheral Aß through intestinal metabolism. Conclusions: The study provides a new avenue for treating brain diseases by excreting disease-causing biohazards using intestinal metabolism.


Subject(s)
Alzheimer Disease , Nanoparticles , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Animals , Antibodies, Monoclonal/pharmacology , Brain/metabolism , Disease Models, Animal , Hazardous Substances/metabolism , Hazardous Substances/pharmacology , Hazardous Substances/therapeutic use , Hyaluronic Acid/metabolism , Ligands , Magnetic Phenomena , Mice , Mice, Transgenic , Plaque, Amyloid/drug therapy , Plaque, Amyloid/metabolism , Silicon Dioxide/pharmacology
5.
Aquat Toxicol ; 252: 106300, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36162202

ABSTRACT

Cadmium (Cd) is considered a priority hazardous substance under the European Community Directive 2013/39 due to its ecotoxicity. The ragworm Hediste diversicolor (O.F. Müller, 1776), a common species in estuaries and coastal lagoons, plays an important ecological role in these ecosystems and is a suitable bioindicator of environmental chemical contamination. In this study, H. diversicolor was chosen as an ecotoxicological model with the aim of evaluating the responses to Cd contamination, considering a multi-biomarker approach (mortality, biometry, behaviour, Cd bioaccumulation, oxidative stress and damage, and energy metabolism). Also, the hypothesis of different tolerances resulting in different responses was evaluated, by collecting worms from three systems distinctly impacted by metal contamination (Mondego estuary, Óbidos Lagoon and Sado estuary - Portugal). Animals were exposed under laboratory conditions to cadmium (10, 50 and 100 µg/L), for 10 days. Significant differences were observed in responses amongst worms originating from the different sites. Organisms from the less impacted systems revealed greater effects on mortality, biomass decrease and burrowing behaviour, as well as higher bioaccumulation potential, after exposure to Cd. Biochemical and behaviour impairments were observed as a consequence of Cd exposure, although not in a concentration-dependant manner. The results obtained in this study reinforce the importance of integrating endpoint responses, at the individual and sub-individual levels, to assess potential changes induced by pollutants in the physiological status and fitness of H. diversicolor and help to predict what their ecological consequences might be.


Subject(s)
Polychaeta , Water Pollutants, Chemical , Animals , Cadmium/toxicity , Cadmium/metabolism , Ecosystem , Environmental Biomarkers , Water Pollutants, Chemical/toxicity , Biomarkers/metabolism , Hazardous Substances/metabolism , Hazardous Substances/pharmacology
6.
Toxicol In Vitro ; 84: 105452, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35931286

ABSTRACT

Sertoli cells play critical roles in regulating spermatogenesis and testis development by providing structural and nutritional support. This study aimed to develop a standard protocol for canine Sertoli cell isolation and culture; and characterize its biological features, functionality, and application of compound toxicity testing. Canine testicles were received from the neuter clinic, and three-step of enzymatic digestion was applied to isolate Sertoli cells. We characterized the growth and purity of Sertoli cells with the expression of SOX9, GATA4, and Clusterin. In addition, we selected cadmium as a model toxicant to evaluate the toxic responses in the newly established Sertoli cells using High-content Analysis (HCA). With our optimized protocol, the purity of isolated Sertoli cells was above 95%, as determined with Sertoli cell-specific protein markers of SOX9 and GATA4. More importantly, primary Sertoli cell populations could be expanded rapidly in vitro, passaged (up to seven), and cryopreserved. The HCA-based assay revealed that cadmium at 1 µM induced both disruptions of cytoskeletal and DNA damage responses. Furthermore, we established an HCA assay with the newly isolated and optimized culture of canine Sertoli cells to evaluate the epigenetic markers of histone modification. We found cadmium-induced differential changes in histone modifications H3Me3K9, H3Me3K36, H4Me3K20, and H4acK5. In summary, we have established the standardized protocol to produce canine Sertoli cells with Sertoli cell-specific phenotype. The isolation and expansion of large quantities of canine Sertoli cells will provide broad applications in studying male infertility, reproductive toxicology, testicular cancer, and cell therapy.


Subject(s)
Sertoli Cells , Testicular Neoplasms , Animals , Cadmium/metabolism , Dogs , Hazardous Substances/metabolism , Humans , Male , Sertoli Cells/metabolism , Spermatogenesis , Testicular Neoplasms/metabolism , Testis/metabolism
7.
Mycotoxin Res ; 38(4): 253-264, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35931866

ABSTRACT

Hazardous chemicals are commonly found in cereals and cereal-based products. However, most studies focus on the individual effects of these mycotoxins or metals, rather than their combined toxicity. The main objective of this study was to evaluate the combined effects of cadmium (Cd) and ochratoxin A (OTA) on intestinal barrier integrity using Caco-2 cells and pig small intestinal epithelial (PSI) cells as models of intestinal epithelial cells and to measure alterations in cell survival and barrier integrity. The combined effects on cell viability were assessed in terms of a combination of index values. These findings showed that co-exposure to Cd + OTA had synergistic effects on Caco-2 and PSI cells at 25%, 50%, and 75% inhibitory concentrations (IC25, IC50, and IC75, respectively) against cell viability. Individual Cd and OTA treatments had no effect, but combined Cd + OTA exposure resulted in synergistic down-regulation of paracellular apical junction complex proteins, such as claudin-1, occludin, and E-cadherin. The current findings indicate that the combined effects of OTA + Cd may have consequences at the gut level, which should not be underestimated when considering their risk to human health.


Subject(s)
Cadmium , Mycotoxins , Humans , Swine , Animals , Caco-2 Cells , Cadmium/toxicity , Cadmium/metabolism , Occludin/metabolism , Claudin-1/metabolism , Epithelial Cells , Mycotoxins/toxicity , Mycotoxins/metabolism , Cadherins/metabolism , Hazardous Substances/metabolism
8.
Chemosphere ; 306: 135576, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35803375

ABSTRACT

The natural and anthropogenic sources of water bodies are contaminated with diverse categories of pollutants such as antibiotics, pharmaceuticals, pesticides, heavy metals, organic compounds, and other industrial chemicals. Depending on the type and the origin of the pollutants, the degree of contamination can be categorized into lower to higher concentrations. Therefore, the removal of hazardous chemicals from the environment is an important aspect. The physical, chemical and biological approaches have been developed and implemented to treat wastewaters. The microbial and algal treatment methods have emerged as a growing field due to their eco-friendly and sustainable approach. Particularly, microalgae emerged as a potential organism for the treatment of contaminated water bodies. The microalgae of the genera Chlorella, Anabaena, Ankistrodesmus, Aphanizomenon, Arthrospira, Botryococcus, Chlamydomonas, Chlorogloeopsis, Dunaliella, Haematococcus, Isochrysis, Nannochloropsis, Porphyridium, Synechococcus, Scenedesmus, and Spirulina reported for the wastewater treatment and biomass production. Microalgae have the potential for adsorption, bioaccumulation, and biodegradation. The microalgal strains can mitigate the hazardous chemicals via their diverse cellular mechanisms. Applications of the microalgae strains were found to be effective for sustainable developments and circular economy due to the production of biomass with the utilization of pollutants.


Subject(s)
Chlorella , Environmental Pollutants , Microalgae , Biomass , Environmental Pollutants/metabolism , Hazardous Substances/metabolism , Microalgae/metabolism , Wastewater , Water/metabolism
9.
Sci Rep ; 11(1): 21069, 2021 10 26.
Article in English | MEDLINE | ID: mdl-34702933

ABSTRACT

AA amyloidosis can be transmitted experimentally in several mammalian and avian species as well as spontaneously between captive animals, even by oral intake of amyloid seeds. Amyloid seeding can cross species boundaries, and fibrils of one kind of amyloid protein may also seed other types. Here we show that meat from Swedish and Italian cattle for consumption by humans often contains AA amyloid and that bovine AA fibrils efficiently cross-seed human amyloid ß peptide, associated with Alzheimer's disease.


Subject(s)
Amyloid beta-Peptides/analysis , Amyloidosis/prevention & control , Food Safety , Hazardous Substances/analysis , Red Meat/analysis , Amyloid beta-Peptides/metabolism , Animals , Cattle , Food Chain , Hazardous Substances/metabolism , Humans , Italy , Serum Amyloid A Protein , Sweden
10.
Biomed Pharmacother ; 143: 112095, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34479017

ABSTRACT

Angiotensin-converting enzyme-2 (ACE2) is one of the major components of the renin-angiotensin system (RAS) and participates in the physiological functions of the cardiovascular system and lungs. Recent studies identified ACE2 as the receptor for the S-protein of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and thus acts as the gateway for viral entry into the human body. Virus infection causes an imbalance in the RAS axis and induces acute lungs injury and fibrosis. Various factors regulate ACE2 expression patterns as well as control its epigenetic status at both transcription and translational levels. This review is mainly focused on the impact of environmental toxicants, drugs, endocrine disruptors, and hypoxia as controlling parameters for ACE2 expression and its possible modulation by epigenetic changes which are marked by DNA methylation, histone modifications, and micro-RNAs (miRNAs) profile. Furthermore, we have emphasized on interventions of various phytochemicals and bioactive compounds as epidrugs that regulate ACE2-S-protein interaction and thereby curb viral infection. Since ACE2 is an important component of the RAAS axis and a crucial entry point of SARS-CoV-2, the dynamics of ACE2 expression in response to various extrinsic and intrinsic factors are of contemporary relevance. We have collated updated information on ACE2 expression modulated by epidrugs, and urge to take over further studies on these important physiological regulators to unravel many more systemic linkages related to both metabolic and infectious diseases, in general and SARS-CoV-2 in particular for further development of targeted interventions.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , COVID-19 , Epigenesis, Genetic , Hazardous Substances , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/metabolism , COVID-19/virology , Gene Expression Regulation/drug effects , Gene Expression Regulation/genetics , Hazardous Substances/adverse effects , Hazardous Substances/metabolism , Humans , SARS-CoV-2/pathogenicity , SARS-CoV-2/physiology , Virus Internalization
11.
F1000Res ; 9: 767, 2020.
Article in English | MEDLINE | ID: mdl-32934808

ABSTRACT

Background: Green micro-alga, Chlamydomonas reinhardtii (a Chlorophyte), can be cultured in the laboratory heterotrophically or photo-heterotrophically in Tris- Phosphate- Acetate (TAP) medium, which contains acetate as the carbon source. Chlamydomonas can convert acetate in the TAP medium to glucose via the glyoxylate cycle, a pathway present in many microbes and higher plants. A novel bacterial strain, CC4533, was isolated from a contaminated TAP agar medium culture plate of a Chlamydomonas wild type strain. In this article, we present our research on the isolation, and biochemical and molecular characterizations of CC4533. Methods: We conducted several microbiological tests and spectrophotometric analyses to biochemically characterize CC4533. The 16S rRNA gene of CC4533 was partially sequenced for taxonomic identification. We monitored the growth of CC4533 on Tris-Phosphate (TP) agar medium (lacks a carbon source) containing different sugars, aromatic compounds and saturated hydrocarbons, to see if CC4533 can use these chemicals as the sole source of carbon. Results: CC4533 is a Gram-negative, non-enteric yellow pigmented, aerobic, mesophilic bacillus. It is alpha-hemolytic and oxidase-positive. CC4533 can ferment glucose, sucrose and lactose, is starch hydrolysis-negative, resistant to penicillin, polymyxin B and chloramphenicol. CC4533 is sensitive to neomycin. Preliminary spectrophotometric analyses indicate that CC4533 produces b-carotenes. NCBI-BLAST analyses of the partial 16S rRNA gene sequence of CC4533 show 99.55% DNA sequence identity to that of Sphingobium yanoikuyae strain PR86 and S. yanoikuyae strain NRB095. CC4533 can use cyclo-chloroalkanes, saturated hydrocarbons present in car motor oil, polyhydroxyalkanoate, and mono- and poly-cyclic aromatic compounds, as sole carbon sources for growth. Conclusions: Taxonomically, CC4533 is very closely related to the alpha-proteobacterium S. yanoikuyae, whose genome has been sequenced. Future research is needed to probe the potential of CC4533 for environmental bioremediation. Whole genome sequencing of CC4533 will confirm if it is a novel strain of S. yanoikuyae or a new Sphingobium species.


Subject(s)
Chlamydomonas/microbiology , Hazardous Substances/metabolism , Hydrocarbons/metabolism , Phylogeny , Sphingomonadaceae/classification , Carbon , DNA, Bacterial/genetics , Pigmentation , RNA, Ribosomal, 16S/genetics , Sphingomonadaceae/isolation & purification , Sphingomonadaceae/metabolism , beta Carotene
12.
Molecules ; 25(17)2020 Sep 01.
Article in English | MEDLINE | ID: mdl-32882977

ABSTRACT

Concern about environmental exposure to hazardous substances has grown over the past several decades, because these substances have adverse effects on human health. Methods used to monitor the biological uptake of hazardous substances and their spatiotemporal behavior in vivo must be accurate and reliable. Recent advances in radiolabeling chemistry and radioanalytical methodologies have facilitated the quantitative analysis of toxic substances, and whole-body imaging can be achieved using nuclear imaging instruments. Herein, we review recent literature on the radioanalytical methods used to study the biological distribution, changes in the uptake and accumulation of hazardous substances, including industrial chemicals, nanomaterials, and microorganisms. We begin with an overview of the radioisotopes used to prepare radiotracers for in vivo experiments. We then summarize the results of molecular imaging studies involving radiolabeled toxins and their quantitative assessment. We conclude the review with perspectives on the use of radioanalytical methods for future environmental research.


Subject(s)
Hazardous Substances/metabolism , Radioisotopes/chemistry , Technology, Radiologic/methods , Animals , Bacteria/metabolism , Humans , Nanostructures , Tissue Distribution
13.
Regul Toxicol Pharmacol ; 117: 104752, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32791089

ABSTRACT

At the 8th conference of Occupational and Environmental Exposure of the Skin to Chemicals (OEESC) (16-18 September 2019) in Dublin, Ireland, several researchers performing skin permeation assays convened to discuss in vitro skin permeability experiments. We, along with other colleagues, all of us hands-on skin permeation researchers, present here the results from our discussions on the available OECD guidelines. The discussions were especially focused on three OECD skin absorption documents, including a recent revision of one: i) OECD Guidance Document 28 (GD28) for the conduct of skin absorption studies (OECD, 2004), ii) Test Guideline 428 (TGD428) for measuring skin absorption of chemical in vitro (OECD, 2004), and iii) OECD Guidance Notes 156 (GN156) on dermal absorption issued in 2011 (OECD, 2011). GN156 (OECD, 2019) is currently under review but not finalized. A mutual concern was that these guidance documents do not comprehensively address methodological issues or the performance of the test, which might be partially due to the years needed to finalize and update OECD documents with new skin research evidence. Here, we summarize the numerous factors that can influence skin permeation and its measurement, and where guidance on several of these are omitted and often not discussed in published articles. We propose several improvements of these guidelines, which would contribute in harmonizing future in vitro skin permeation experiments.


Subject(s)
Congresses as Topic/standards , Environmental Exposure/standards , Guideline Adherence/standards , Occupational Exposure/standards , Organisation for Economic Co-Operation and Development/standards , Skin Absorption/drug effects , Environmental Exposure/prevention & control , Hazardous Substances/metabolism , Hazardous Substances/toxicity , Humans , Ireland , Occupational Exposure/prevention & control , Skin Absorption/physiology
14.
Regul Toxicol Pharmacol ; 117: 104764, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32798611

ABSTRACT

Screening certain environmental chemicals for their ability to interact with endocrine targets, including the androgen receptor (AR), is an important global concern. We previously developed a model using a battery of eleven in vitro AR assays to predict in vivo AR activity. Here we describe a revised mathematical modeling approach that also incorporates data from newly available assays and demonstrate that subsets of assays can provide close to the same level of predictivity. These subset models are evaluated against the full model using 1820 chemicals, as well as in vitro and in vivo reference chemicals from the literature. Agonist batteries of as few as six assays and antagonist batteries of as few as five assays can yield balanced accuracies of 95% or better relative to the full model. Balanced accuracy for predicting reference chemicals is 100%. An approach is outlined for researchers to develop their own subset batteries to accurately detect AR activity using assays that map to the pathway of key molecular and cellular events involved in chemical-mediated AR activation and transcriptional activity. This work indicates in vitro bioactivity and in silico predictions that map to the AR pathway could be used in an integrated approach to testing and assessment for identifying chemicals that interact directly with the mammalian AR.


Subject(s)
Androgen Receptor Antagonists/toxicity , Androgens/toxicity , Hazardous Substances/toxicity , Models, Theoretical , Receptors, Androgen , Androgen Receptor Antagonists/metabolism , Androgens/metabolism , Animals , Environmental Exposure/prevention & control , Environmental Exposure/statistics & numerical data , Hazardous Substances/metabolism , High-Throughput Screening Assays/methods , Humans , Receptors, Androgen/metabolism
15.
Chemosphere ; 254: 126746, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32339800

ABSTRACT

A variety of chemicals are capable of provoking mitochondrial dysfunction and thereby contribute to metabolic disorder related effects in wildlife and human. For better identifying new mitochondrial toxicants and assessing mitochondria-related risk, an in-depth understanding of toxic mechanisms and biomarkers should be attained. In the current study, a representative mitotoxicant, azoxystrobin, was assessed for lethal and sublethal outcomes in Chironomus dilutus after 96-h exposure and the toxic mechanism was explored. Global transcriptomic profiles by RNA-sequencing revealed that ampk, acc1, atp2a, gsk3b, pi3k, fak, atr, chk1, and map3k5 were the key genes which involved in the toxic action of azoxystrobin and could serve as potential molecular biomarkers. A major network of common toxicity pathways was then developed for mitotoxicants towards aquatic insects. In particular, calcium ion-PI3K/AKT and cAMP-AMPK-lethality pathways were demonstrated, in addition to the well-known mitochondrial electron transfer-oxidative damage-apoptosis pathway. These analyses could help developing adverse outcome pathways that integrate toxicological information at various levels and support more effective risk assessment and management of mitotoxicants.


Subject(s)
Chironomidae/physiology , Hazardous Substances/toxicity , Mitochondria/physiology , Oxidative Stress/physiology , Animals , Biomarkers/metabolism , Chironomidae/drug effects , Hazardous Substances/metabolism , Humans , Mitochondria/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Pyrimidines , Strobilurins , Toxicity Tests , Transcriptome
16.
Hum Exp Toxicol ; 39(1): 14-36, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31578097

ABSTRACT

The transient receptor potential ankyrin 1 (TRPA1) ion channel is a sensor for irritant chemicals, has ancient lineage, and is distributed across animal species including humans, where it features in many organs. Its activation by a diverse panel of electrophilic molecules (TRPA1 agonists) through electrostatic binding and/or covalent attachment to the protein causes the sensation of pain. This article reviews the species differences between TRPA1 channels and their responses, to assess the suitability of different animals to model the effects of TRPA1-activating electrophiles in humans, referring to common TRPA1 activators (exogenous and endogenous) and possible mechanisms of action relating to their toxicology. It concludes that close matching of in vitro and in vivo models will help optimise the identification of relevant biochemical and physiological responses to benchmark the efficacy of potential therapeutic drugs, including TRPA1 antagonists, to counter the toxic effects of those electrophiles capable of harming humans. The analysis of the species issue provided should aid the development of medical treatments to counter poisoning by such chemicals.


Subject(s)
Disease Models, Animal , Hazardous Substances/toxicity , TRPA1 Cation Channel/metabolism , Animals , Hazardous Substances/metabolism , Humans , Models, Molecular , Protein Conformation , TRPA1 Cation Channel/agonists , TRPA1 Cation Channel/chemistry , TRPA1 Cation Channel/genetics
17.
Environ Pollut ; 256: 113550, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31706782

ABSTRACT

Per- and polyfluoroalkyl substances (PFASs) have been used for decades within industrial processes and consumer products, resulting in frequent detection within the environment. Using zebrafish embryos, we screened 38 PFASs for developmental toxicity and revealed that perfluorooctanesulfonamide (PFOSA) was the most potent developmental toxicant, resulting in elevated mortality and developmental abnormalities following exposure from 6 to 24 h post fertilization (hpf) and 6 to 72 hpf. PFOSA resulted in a concentration-dependent increase in mortality and abnormalities, with surviving embryos exhibiting a >12-h delay in development at 24 hpf. Exposures initiated at 0.75 hpf also resulted in a concentration-dependent delay in epiboly, although these effects were not driven by a specific sensitive window of development. We relied on mRNA-sequencing to identify the potential association of PFOSA-induced developmental delays with impacts on the embryonic transcriptome. Relative to stage-matched vehicle controls, these data revealed that pathways related to hepatotoxicity and lipid transport were disrupted in embryos exposed to PFOSA from 0.75 to 14 hpf and 0.75 to 24 hpf. Therefore, we measured liver area as well as neutral lipids in 128-hpf embryos exposed to vehicle (0.1% DMSO) or PFOSA from 0.75 to 24 hpf and clean water from 24 to 128 hpf, and showed that PFOSA exposure from 0.75 to 24 hpf resulted in a decrease in liver area and increase in yolk sac neutral lipids at 128 hpf. Overall, our findings show that early exposure to PFOSA adversely impacts embryogenesis, an effect that may lead to altered lipid transport and liver development.


Subject(s)
Fluorocarbons/toxicity , Sulfonamides/toxicity , Water Pollutants, Chemical/toxicity , Animals , Embryo, Nonmammalian/drug effects , Embryonic Development/drug effects , Fluorocarbons/metabolism , Hazardous Substances/metabolism , RNA, Messenger/metabolism , Toxicity Tests , Zebrafish/embryology , Zebrafish/metabolism , Zebrafish Proteins/metabolism
18.
Environ Pollut ; 254(Pt B): 112871, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31465905

ABSTRACT

Leachates from municipal landfills are formed as infiltration waters flowing through the landfill. They contain toxic, dissolved products of biochemical reactions taking place in the deposit. They cause soil and groundwater pollution. It is necessary to take them out of the landfill cover and utilize toxins contained therein, in particular heavy metals. Such processes are conducted with the use of microorganisms. Due to the content of toxic compounds, introducing leachates into the process of biological purification poses a threat to the microorganisms used in these processes. An alternative to microbial co-treatment of sludge and leachate as well as soil contaminated with communal leachate is to use red hybrid of California (Eisenia fetida Sav.), an earthworm resistant to environmental toxins, in particular heavy metals. The aim of the conducted research is to demonstrate the possibility of using red hybrid of California in leachate bioutilization as a complementary or alternative method to the process of leachate utilization with the use of microorganisms. The obtained results led to the conclusion that Eisenia fetida accumulates environmental toxins well. By collecting and processing them in the tissues, it remedies the substrate and retains long life and fertility, and the ability to reproduce. The research demonstrated high dynamics of population growth (from 25 individuals in the initial deposit to 298 individuals after six months of research). These properties are related to the presence of enzyme proteins from the metallothionein group in the gastrointestinal tract cells. Packing heavy metals found in leachates into the metallothionein coat limits their toxic effect on earthworm tissues, which confirms the possibility of using earthworms in the processes of detoxification of municipal leachate.


Subject(s)
Environmental Restoration and Remediation/methods , Oligochaeta/metabolism , Animals , Biodegradation, Environmental , California , Hazardous Substances/metabolism , Metals, Heavy/analysis , Metals, Heavy/metabolism , Refuse Disposal , Waste Disposal Facilities
19.
Environ Sci Pollut Res Int ; 26(14): 14521-14533, 2019 May.
Article in English | MEDLINE | ID: mdl-30877528

ABSTRACT

Muscle, liver and kidney of 21 Barbary sheep (Ammotragus lervia) from Mosor Mountain, Croatia, were sampled to quantify the activity of caesium and potassium radionuclides and five toxic and ten essential stabile elements in order to establish reference values for this species and to evaluate the potential of Barbary sheep tissues to reflect environmental pollution. We also assessed seasonal diet (botanical composition and dry matter content) of Barbary sheep based on analyses of a rumen content of culled animals. None of the 19 plant species (mostly grasses) identified as part of the Barbary sheep diet is known as a stabile element or radionuclide hyperaccumulator. Measured levels reflected low environmental pollution with arsenic, cadmium, mercury and lead, with levels generally less than those reported for wild herbivorous ungulates. Methodological differences (detection limit of elements in muscle) were shown to hamper interpretation and comparison of the Toxic Contamination Index (TCI) values with those published for other species. There was no homeostasis disturbance of trace elements in Barbary sheep, either due to inadequate intake via food or as an adverse effect due to a high toxic metal(loid) burden. Consumption of the muscle and liver of wild Barbary sheep can be considered safe for the health of adult consumers regarding toxic metal(loid)s and radioactive caesium, though the liver should be avoided as a food item in vulnerable population groups due to the possible adverse effects of cadmium and lead. Otherwise, muscle and liver are a rich source of copper, iron, selenium and zinc for consumers and, as such, can benefit the overall dietary intake of essential elements.


Subject(s)
Environmental Exposure/analysis , Environmental Pollutants/metabolism , Radioactive Pollutants/metabolism , Radioisotopes/metabolism , Animals , Arsenic/analysis , Biomarkers/metabolism , Cadmium/analysis , Cesium/analysis , Cesium/metabolism , Cesium Radioisotopes/metabolism , Copper/analysis , Croatia , Diet , Environmental Biomarkers , Environmental Exposure/statistics & numerical data , Food Contamination/analysis , Food Contamination/statistics & numerical data , Hazardous Substances/metabolism , Iron/analysis , Mercury/analysis , Potassium/analysis , Potassium/metabolism , Potassium Radioisotopes/metabolism , Radiation Exposure/statistics & numerical data , Radioisotopes/analysis , Ruminants , Selenium/analysis , Sheep , Trace Elements/analysis , Trace Elements/metabolism , Zinc/analysis
20.
Sci Total Environ ; 665: 937-943, 2019 May 15.
Article in English | MEDLINE | ID: mdl-30893753

ABSTRACT

Permeation of oxides of nitrogen and sulfur gases through skin and the consequences of dermal exposure are still poorly understood. We measured the penetration profile of three common industrial gases through skin, for short-term exposures relevant to HAZMAT scenarios. Time variations of gas concentration, clothing effects, temperature and humidity on epidermal absorption and penetration were assessed. Fabric off-gassing profiles were also investigated. The results show oxides of nitrogen (NO and NO2) at airborne concentrations up to lethal inhalation levels (e.g. 3000 ppm) have little skin penetration ability. Skin absorption and reservoir effects were noted. Skin exposed to SO2 (3000 ppm/30 min) shows negligible skin absorption or penetration. Fabric on skin marginally increased SO2 absorption and subsequent ventilation did not reduce the absorbed fraction. Increased temperature and humidity had limited additional effect on skin penetration. Importantly, clothing demonstrated sink properties, especially for SO2. Short-term skin exposure relevant to accidents will not significantly contribute to body burden. The greatest concern will likely be off-gassing of chemical-laden fabric for asthma suffers. The risk-based management approach is to avoid potential secondary inhalation from fabric off-gassing by removal of outer layer of bulky clothing. Decontamination and moving into an area of enhanced ventilation may also be advised.


Subject(s)
Air Pollutants/metabolism , Environmental Exposure , Epidermis/metabolism , Nitrogen Oxides/metabolism , Skin Absorption , Sulfur Oxides/metabolism , Clothing , Hazardous Substances/adverse effects , Hazardous Substances/metabolism , Humans , Humidity , In Vitro Techniques , Temperature
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