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Toxics May 2024Soil contamination of polycyclic aromatic hydrocarbons (PAHs), especially caused by the mixture of two or more PAHs, raised great environmental concerns. However,...
Soil contamination of polycyclic aromatic hydrocarbons (PAHs), especially caused by the mixture of two or more PAHs, raised great environmental concerns. However, research on the migration and transformation processes of PAHs in soils and their interactions with native communities is limited. In this work, soil samples from uncontaminated sites around the industrial parks in Handan, Hengshui, and Shanghai were artificially supplemented with three concentrations of anthracene (Ant), 9-chloroanthracene (9-ClAnt), benzopyrene (BaP), and chrysene (Chr). Ryegrass was planted to investigate the degradation of PAHs and its interaction with native soil organisms in the constructed ryegrass-microbe-soil microcosmic system. The bacterial and fungal communities in soil were affected by PAHs; their species diversity and relative abundance changed after exposure to different concentrations of PAHs, among which , , , and bacteria were correlated to the degradation of PAHs. On the 56th day, the contents of BaP, Chr, and Ant decreased with the degradation process, while the degradation of 9-ClAnt was limited. Nineteen intermediates, including hydroxylation and carboxylated compounds, were identified. The present research would help clarify the potential interactions between PAHs and native organisms in contaminated sites, providing fundamental information for evaluating the transformation risks of PAHs in the natural environment.
PubMed: 38787140
DOI: 10.3390/toxics12050361 -
Chemosphere Jun 2024The release of polycyclic aromatic hydrocarbons (PAHs) into the environment is posing a threat to ecosystems and human health. Benzo(a)pyrene (BaP) is considered a...
The release of polycyclic aromatic hydrocarbons (PAHs) into the environment is posing a threat to ecosystems and human health. Benzo(a)pyrene (BaP) is considered a biomarker of PAH exposure and is classified as a Group 1 carcinogen. However, it was not known whether BaP is mutagenic, i.e. induces inherited germline mutations. In this study, we used a recently established method, which combines short-term mutation accumulation lines (MAL) with whole genome sequencing (WGS) to assess mutagenicity in the non-biting midge Chironomus riparius. The mutagenicity analysis was supplemented by an evaluation of the development of population fitness in three successive generations in the case of chronic exposure to BaP at a high concentration (100 μg/L). In addition, the level of ROS-induced oxidative stress was examined in vivo. Exposure to the higher BaP concentration led to an increase in germline mutations relative to the control, while the lower concentration showed no mentionable effect. Against expectations, BaP exposure decreased ROS-level compared to the control and is thus probably not responsible for the increased mutation rate. Likewise, the higher BaP concentration decreased fitness measured as population growth rate per day (PGR) significantly over all generations, without signs of rapid evolutionary adaptations. Our results thus highlighted that high BaP exposure may influence the evolutionary trajectory of organisms.
Topics: Animals; Benzo(a)pyrene; Chironomidae; Oxidative Stress; Water Pollutants, Chemical; Reactive Oxygen Species; Whole Genome Sequencing; Mutagens; Polycyclic Aromatic Hydrocarbons; Mutagenicity Tests
PubMed: 38710409
DOI: 10.1016/j.chemosphere.2024.142242 -
Ecotoxicology and Environmental Safety Jun 2024Microplastics (MPs) and benzo[a]pyrene (B[a]P) are prevalent environmental pollutants. Numerous studies have extensively reported their individual adverse effects on...
Microplastics (MPs) and benzo[a]pyrene (B[a]P) are prevalent environmental pollutants. Numerous studies have extensively reported their individual adverse effects on organisms. However, the combined effects and mechanisms of exposure in mammals remain unknown. Thus, this study aims to investigate the potential effects of oral administration of 0.5μm polystyrene (PS) MPs (1 mg/mL or 5 mg/mL), B[a]P (1 mg/mL or 5 mg/mL) and combined (1 mg/mL or 5 mg/mL) on 64 male SD rats by gavage method over 6-weeks. The results demonstrate that the liver histopathological examination showed that the liver lobules in the combined (5 mg/kg) group had blurred and loose boundaries, liver cord morphological disorders, and significant steatosis. The levels of AST, ALT, TC, and TG in the combined dose groups were significantly higher than those in the other groups, the combined (5 mg/kg) group had the lowest levels of antioxidant enzymes and the highest levels of oxidants. The expression of Nrf2 was lowest and the expression of P38, NF-κB, and TNF-α was highest in the combined (5 mg/kg) group. In conclusion, these findings indicate that the combination of PSMPs and B[a]P can cause the highest levels of oxidative stress and elicit markedly enhanced toxic effects, which cause severe liver damage.
Topics: Animals; Oxidative Stress; Benzo(a)pyrene; Microplastics; Male; Polystyrenes; Liver; Rats, Sprague-Dawley; Rats; Environmental Pollutants; Antioxidants; NF-kappa B; NF-E2-Related Factor 2
PubMed: 38705037
DOI: 10.1016/j.ecoenv.2024.116390 -
Ecotoxicology and Environmental Safety Jun 2024Environmental benzo(a)pyrene (BaP) and itsmetabolite benzo(a)pyrene-7, 8-dihydrodiol-9, 10-epoxide (BPDE), classic endocrine disrupting chemical and persistent organic...
Environmental benzo(a)pyrene (BaP) and itsmetabolite benzo(a)pyrene-7, 8-dihydrodiol-9, 10-epoxide (BPDE), classic endocrine disrupting chemical and persistent organic pollutant, could cause miscarriage. However, the detailed mechanisms are still largely unclear and should be further explored. In this study, we discovered that exposure of trophoblast cells with BPDE could suppressed cell invasion/migration by inhibiting MEST/VIM (Vimentin) pathway. Moreover, BPDE exposure also increased lnc-HZ01 expression level, which further inhibited MEST/VIM pathway and then suppressed invasion/migration. Knockdown of lnc-HZ01 or overexpression of MEST could efficiently rescue invasion/migration of BPDE-exposed Swan 71 cells. Furthermore, lnc-HZ01 was highly expressed and MEST/VIM were lowly expressed in recurrent miscarriage (RM) villous tissues compared with healthy control (HC) group. Finally, we also found that BaP exposure inhibited murine Mest/Vim pathway in placental tissues and induced miscarriage in BaP-exposed mice. Therefore, the regulatory mechanisms were similar in BPDE-exposed human trophoblast cells, RM villous tissues, and placental tissues of BaP-exposed mice with miscarriage, building a bridge to connect BaP/BPDE exposure, invasion/migration, and miscarriage. This study provided novel insights in the toxicological effects and molecular mechanisms of BaP/BPDE-induced miscarriage, which is helpful for better elucidating the toxicological risks of BaP/BPDE on female reproduction.
Topics: Trophoblasts; Female; Animals; Cell Movement; Benzo(a)pyrene; Humans; Mice; Down-Regulation; 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; Pregnancy; Endocrine Disruptors; Environmental Pollutants; Cell Line; Abortion, Spontaneous
PubMed: 38701656
DOI: 10.1016/j.ecoenv.2024.116409 -
Scientific Reports Apr 2024Smoking of classic cigarettes has been well-established as a health risk factor, including cardiovascular, neurological, and pulmonary diseases. Adverse effects on human...
Smoking of classic cigarettes has been well-established as a health risk factor, including cardiovascular, neurological, and pulmonary diseases. Adverse effects on human reproduction have also been shown. Smokers are assumed to have a significantly lower chance of pregnancy, however, the impact of smoking on medically assisted reproduction (MAR) treatment outcomes is controversial. Moreover, smoking habits have changed during the last decades since e-cigarettes and hookahs, or water pipes, have become very popular, yet little is known regarding vaping or hookah-smoking patients undergoing MAR treatments. This prospective study aimed to examine the presence of benzo[a]pyrene, nicotine, and its main metabolite, cotinine, in human follicular fluid (FF) in non-smoking, smoking, and vaping/hookah-smoking patients and to evaluate the impact on female fertility. Human FF samples were collected from 320 women subjected to intracytoplasmic sperm injection (ICSI) cycles due to male subfertility. Gas chromatography combined with mass spectrometry was used to analyse the presence of benzo[a]pyrene, nicotine, and cotinine. A questionnaire was provided to assess patient consumption behaviour and to identify (1) non-smoking patients, (2) patients who consumed cigarettes, and (3) patients with exclusive consumption of e-cigarettes or hookahs. Data were analysed using linear and logistic regression, Fisher's exact test, and the Mann-Whitney U Test. Nicotine was present in 22 (6.8%) and cotinine in 65 (20.3%) of the 320 samples. The nicotine and cotinine concentrations per sample ranged from 0 to 26.3 ng/ml and 0-363.0 ng/ml, respectively. Benzo[a]pyrene was not detectable in any of the samples analysed. Nicotine and cotinine were also present in the FF of patients with exclusive consumption of e-cigarettes or hookahs. The clinical pregnancy rate, fertilization and maturation rates, and number of oocytes per oocyte pick-up were not statistically significantly different between non-smoking, smoking, or vaping/hookah-smoking patients. Smoking and the accumulation of smoking toxins in the FF have no impact on the outcome of MAR treatments-neither the clinical pregnancy rate, maturation and fertilization rates, nor the number of retrieved oocytes were affected. For the first time, nicotine and cotinine were quantified in the FF of patients exclusively vaping e-cigarettes or smoking hookahs. Since vaping liquids and hookah tobaccos contain potentially harmful substances, other adverse effects cannot be excluded.Trial registration ClinicalTrials.gov Identifier: NCT03414567.
Topics: Humans; Female; Adult; Reproductive Techniques, Assisted; Cotinine; Nicotine; Electronic Nicotine Delivery Systems; Prospective Studies; Pregnancy; Follicular Fluid; Benzo(a)pyrene; Male; Vaping; Water Pipe Smoking; Smoking
PubMed: 38671174
DOI: 10.1038/s41598-024-60251-y -
Ecotoxicology and Environmental Safety Jun 2024PIWI-interacting RNAs (piRNAs) is an emerging class of small non-coding RNAs that has been recently reported to have functions in infertility, tumorigenesis, and...
PIWI-interacting RNAs (piRNAs) is an emerging class of small non-coding RNAs that has been recently reported to have functions in infertility, tumorigenesis, and multiple diseases in humans. Previously, 5 toxicity pathways were proposed from hundreds of toxicological studies that underlie BaP-induced lung injuries, and a "Bottom-up" approach was established to identify small non-coding RNAs that drive BaP-induced pulmonary effects by investigating the activation of these pathways in vitro, and the expression of the candidate microRNAs were validated in tissues of patients with lung diseases from publications. Here in this study, we employed the "Bottom-up" approach to identifying the roles of piRNAs and further validated the mechanisms in vivo using mouse acute lung injury model. Specifically, by non-coding RNA profiling in in vitro BaP exposure, a total of 3 suppressed piRNAs that regulate 5 toxicity pathways were proposed, including piR-004153 targeting CYP1A1, FGFR1, ITGA5, IL6R, NGRF, and SDHA, piR-020326 targeting CDK6, and piR-020388 targeting RASD1. Animal experiments demonstrated that tail vein injection of respective formulated agomir-piRNAs prior to BaP exposure could all alleviate acute lung injury that was shown by histopathological and biochemical evidences. Immunohistochemical evaluation focusing on NF-kB and Bcl-2 levels showed that exogenous piRNAs protect against BaP-induced inflammation and apoptosis, which further support that the inhibition of the 3 piRNAs had an important impact on BaP-induced lung injuries. This mechanism-driven, endpoint-supported result once again confirmed the plausibility and efficiency of the approach integrating in silico, in vitro, and in vivo evidences for the purpose of identifying key molecules.
Topics: Animals; Mice; RNA, Small Interfering; Benzo(a)pyrene; Acute Lung Injury; Lung Injury; Male; Mice, Inbred C57BL; Humans; Piwi-Interacting RNA
PubMed: 38636406
DOI: 10.1016/j.ecoenv.2024.116330 -
Ecotoxicology and Environmental Safety May 2024Benzo(a)pyrene (BaP) can be detected in the human placenta. However, little is known about the effects of BaP exposure on different placental cells under various...
Benzo(a)pyrene (BaP) can be detected in the human placenta. However, little is known about the effects of BaP exposure on different placental cells under various conditions. In this study, we aimed to investigate the effects of BaP on mitochondrial function, pyrin domain-containing protein 3 (NLRP3) inflammasome, and apoptosis in three human trophoblast cell lines under normoxia, hypoxia, and inflammatory conditions. JEG-3, BeWo, and HTR-8/SVneo cell lines were exposed to BaP under normoxia, hypoxia, or inflammatory conditions for 24 h. After treatment, we evaluated cell viability, apoptosis, aryl hydrocarbon receptor (AhR) protein and cytochrome P450 (CYP) gene expression, mitochondrial function, including mitochondrial DNA copy number (mtDNAcn), mitochondrial membrane potential (ΔΨm), intracellular adenosine triphosphate (iATP), and extracellular ATP (eATP), nitric oxide (NO), NLPR3 inflammasome proteins, and interleukin (IL)-1β. We found that BaP upregulated the expression of AhR or CYP genes to varying degrees in all three cell lines. Exposure to BaP alone increased ΔΨm in all cell lines but decreased NO in BeWo and HTR-8/SVneo, iATP in HTR-8/SVneo, and cell viability in JEG-3, without affecting apoptosis. Under hypoxic conditions, BaP did not increase the expression of AhR and CYP genes in JEG-3 cells but increased CYP gene expression in two others. Pro-inflammatory conditions did not affect the response of the 3 cell lines to BaP with respect to the expression of CYP genes and changes in the mitochondrial function and NLRP3 inflammasome proteins. In addition, in HTR-8/SVneo cells, BaP increased IL-1β secretion in the presence of hypoxia and poly(I:C). In conclusion, our results showed that BaP affected mitochondrial function in trophoblast cell lines by increasing ΔΨm. This increased ΔΨm may have rescued the trophoblast cells from activation of the NLRP3 inflammasome and apoptosis after BaP treatment. We also observed that different human trophoblast cell lines had cell type-dependent responses to BaP exposure under normoxia, hypoxia, or pro-inflammatory conditions.
Topics: Humans; Benzo(a)pyrene; Placenta; Cell Line; Female; Pregnancy; Apoptosis; Trophoblasts; Receptors, Aryl Hydrocarbon; Cell Survival; NLR Family, Pyrin Domain-Containing 3 Protein; Inflammasomes; Mitochondria; Inflammation; Cell Hypoxia; Membrane Potential, Mitochondrial; Cytochrome P-450 Enzyme System; Basic Helix-Loop-Helix Transcription Factors
PubMed: 38579532
DOI: 10.1016/j.ecoenv.2024.116287 -
Mutation Research 2024Environmental and occupational exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with adverse health effects in humans. Uncertainty exists regarding the...
Environmental and occupational exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with adverse health effects in humans. Uncertainty exists regarding the causation of urinary bladder cancer by benzo[a]pyrene (B[a]P) due to a lack of sufficient data. In this work, we focused on in-vitro DNA damage and the formation of micronuclei and chromosomal aberrations as predictors of cancer risk, applying a wide range of dosages and time periods to quantify the onset, intensity, and duration of the response. We chose two urothelial cell types to compare susceptibility and the ability to increase the malignity of a pre-existing bladder cancer: a cancer cell line (T24) and a pooled sample of primary urinary bladder epithelia cells (PUBEC) from pigs. The highest level of DNA damage assessed by comet assay was observed following 24-h treatment in both cell types, whereas PUBEC cells were clearly more susceptible. Even 4-h treatment induced DNA damage in PUBEC cells with benchmark doses of 0.0027 µM B[a]P and 0.00023 µM after 4-h and 24-h exposure, respectively. Nearly no effect was observed for periods of 48 h. The frequency of micronucleus formation increased more markedly in T24 cells, particularly with 24-h treatment. In PUBEC cells, 48-h exposure notably induced the formation of nucleoplasmic bridges and nuclear buds. Even though only one biological replicate was studied due to the sophisticated study design, our results give a strong indication of the potential of B[a]P to induce and increase malignity in human-relevant cell types.
Topics: Benzo(a)pyrene; DNA Damage; Pilot Projects; Animals; Urothelium; Chromosomal Instability; Humans; Swine; Micronucleus Tests; Dose-Response Relationship, Drug; Chromosome Aberrations; Urinary Bladder Neoplasms; Time Factors; Comet Assay; Cell Line, Tumor; Urinary Bladder
PubMed: 38569440
DOI: 10.1016/j.mrfmmm.2024.111855 -
Cortical lipid metabolic pathway alteration of early Alzheimer's disease and candidate drugs screen.European Journal of Medical Research Mar 2024Lipid metabolism changes occur in early Alzheimer's disease (AD) patients. Yet little is known about metabolic gene changes in early AD cortex.
BACKGROUND
Lipid metabolism changes occur in early Alzheimer's disease (AD) patients. Yet little is known about metabolic gene changes in early AD cortex.
METHODS
The lipid metabolic genes selected from two datasets (GSE39420 and GSE118553) were analyzed with enrichment analysis. Protein-protein interaction network construction and correlation analyses were used to screen core genes. Literature analysis and molecular docking were applied to explore potential therapeutic drugs.
RESULTS
60 lipid metabolic genes differentially expressed in early AD patients' cortex were screened. Bioinformatics analyses revealed that up-regulated genes were mainly focused on mitochondrial fatty acid oxidation and mediating the activation of long-chain fatty acids, phosphoproteins, and cholesterol metabolism. Down-regulated genes were mainly focused on lipid transport, carboxylic acid metabolic process, and neuron apoptotic process. Literature reviews and molecular docking results indicated that ACSL1, ACSBG2, ACAA2, FABP3, ALDH5A1, and FFAR4 were core targets for lipid metabolism disorder and had a high binding affinity with compounds including adenosine phosphate, oxidized Photinus luciferin, BMS-488043, and candidate therapeutic drugs especially bisphenol A, benzo(a)pyrene, ethinyl estradiol.
CONCLUSIONS
AD cortical lipid metabolism disorder was associated with the dysregulation of the PPAR signaling pathway, glycerophospholipid metabolism, adipocytokine signaling pathway, fatty acid biosynthesis, fatty acid degradation, ferroptosis, biosynthesis of unsaturated fatty acids, and fatty acid elongation. Candidate drugs including bisphenol A, benzo(a)pyrene, ethinyl estradiol, and active compounds including adenosine phosphate, oxidized Photinus luciferin, and BMS-488043 have potential therapeutic effects on cortical lipid metabolism disorder of early AD.
Topics: Humans; Alzheimer Disease; Molecular Docking Simulation; Benzo(a)pyrene; Fatty Acids; Metabolic Networks and Pathways; Lipid Metabolism Disorders; Ethinyl Estradiol; Adenine Nucleotides; Luciferins; Pyruvic Acid; Phenols; Indoles; Benzhydryl Compounds; Piperazines
PubMed: 38528586
DOI: 10.1186/s40001-024-01730-w -
Chemosphere Apr 2024Polyaromatic benzo[a]pyrene (B[a]P) is a toxic carcinogenic environmental pollutant, and the use of microorganisms to remediate B[a]P contamination is considered to be...
Polyaromatic benzo[a]pyrene (B[a]P) is a toxic carcinogenic environmental pollutant, and the use of microorganisms to remediate B[a]P contamination is considered to be one of the most effective strategies. However, there is still a gap in studying the metabolic remodeling of microorganisms under B[a]P stress. In this study, our systematically investigated the effects of B[a]P on the metabolism of Bacillus subtilis MSC4 based on transcriptomic, molecular and biochemical analyses. The results showed that in response to B[a]P stress, MSC4 formed more biofilm matrix and endospores, the structure of the endospores also was changed, which led to a reduction in their resistance and made them more difficult to germinate. In addition to an increase in glycolysis activity, the activities of tricarboxylic acid cycle, pentose phosphate pathway and the electron transport chain were decreased. B[a]P stress forced MSC4 to strengthen arginine synthesis, urea cycle, and urea decomposition, meanwhile, synthesize more ribonucleotides. The activity of DNA replication, transcription activities and the expression of multiple ribosomal protein genes were reduced. Moreover, all of the reported enzymes involved in B[a]P degradation showed decreased transcript abundance, and the degradation of B[a]P caused significant up-regulation of the gene expression of the acid inducible enzyme OxdC and the synthesis of acetoin. In addition, the cytotoxicity of B[a]P to bacteria was directly displayed in four aspects: increased intracellular level of reactive oxygen species (ROS), elevated cell membrane permeability, up-regulation of the cell envelope stress-sensing two-component system LiaRS, and downregulation of siderophores biosynthesis. Finally, B[a]P also caused morphological changes in the cells, with some cells exhibiting significant deformation and concavity. These findings provide effective research directions for targeted improvement the cellular activity of B[a]P-degrading strains, and is beneficial for further application of microorganisms to remediate B[a]P -contaminated soils.
Topics: Benzo(a)pyrene; Bacillus subtilis; Glycolysis; Gene Expression Profiling; Urea
PubMed: 38462177
DOI: 10.1016/j.chemosphere.2024.141637