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2.
Biomed Environ Sci ; 37(5): 479-493, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38843921

RESUMO

Objective: To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons (PAHs) during critical brain development and explore their potential link with the intestinal microbiota. Methods: Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs (OH-PAHs) in 36-month-old children. Subsequently, 37 children were categorized into low- and high-exposure groups based on the sum of the ten OH-PAHs. Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples. Furthermore, fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq. Results: The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group (variable importance for projection > 1, P < 0.05). Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene, fluorine, and phenanthrene ( r = 0.336-0.531). The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states, including amino acid, lipid, and nucleotide metabolism. Additionally, these distinct metabolites were significantly associated with specific intestinal flora abundances ( r = 0.34-0.55), which were mainly involved in neurodevelopment. Conclusion: Higher PAH exposure in young children affected metabolic homeostasis, particularly that of certain gut microbiota-derived metabolites. Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.


Assuntos
Microbioma Gastrointestinal , Hidrocarbonetos Policíclicos Aromáticos , Humanos , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/urina , Masculino , Pré-Escolar , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/toxicidade , Poluentes Ambientais/metabolismo , Metabolômica , Metaboloma/efeitos dos fármacos
3.
J Environ Sci (China) ; 145: 1-12, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38844310

RESUMO

The potential association between colorectal cancer (CRC) and environmental pollutants is worrisome. Previous studies have found that some perfluoroalkyl acids, including perfluorooctane sulfonate (PFOS), induced colorectal tumors in experimental animals and promoted the migration of and invasion by CRC cells in vitro, but the underlying mechanism is unclear. Here, we investigated the effects of PFOS on the proliferation and migration of CRC cells and the potential mechanisms involving activating the PI3K/Akt-NF-κB signal pathway and epithelial-mesenchymal transition (EMT). It was found that PFOS promoted the growth and migration of HCT116 cells at non-cytotoxic concentrations and increased the mRNA expression of the migration-related angiogenic cytokines vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8). In a mechanistic investigation, the up-stream signal pathway PI3K/Akt-NF-κB was activated by PFOS, and the process was suppressed by LY294002 (PI3K/Akt inhibitor) and BAY11-7082 (NF-κB inhibitor) respectively, leading to less proliferation of HCT116 cells. Furthermore, matrix metalloproteinases (MMP) and EMT-related markers were up-regulated after PFOS exposure, and were also suppressed respectively by LY294002 and BAY11-7082. Moreover, the up-regulation of EMT markers was suppressed by a MMP inhibitor GM6001. Taken together, our results indicated that PFOS promotes colorectal cancer cell migration and proliferation by activating the PI3K/Akt-NF-κB signal pathway and epithelial-mesenchymal transition. This could be a potential toxicological mechanism of PFOS-induced malignant development of colorectal cancer.


Assuntos
Ácidos Alcanossulfônicos , Movimento Celular , Neoplasias Colorretais , Transição Epitelial-Mesenquimal , Fluorocarbonos , Fluorocarbonos/toxicidade , Ácidos Alcanossulfônicos/toxicidade , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Colorretais/patologia , Humanos , Movimento Celular/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Células HCT116 , Proteínas Proto-Oncogênicas c-akt/metabolismo , NF-kappa B/metabolismo , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral
4.
Environ Geochem Health ; 46(7): 238, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849627

RESUMO

Microplastics (MPs) are defined as plastic particles or fragments with a diameter of less than 5 mm. These particles have been identified as causing male reproductive toxicity, although the precise mechanism behind this association is yet to be fully understood. Recent research has found that exposure to polystyrene microplastics (PS-MPs) can disrupt spermatogenesis by impacting the integrity of the blood-testis barrier (BTB), a formidable barrier within mammalian blood tissues. The BTB safeguards germ cells from harmful substances and infiltration by immune cells. However, the disruption of the BTB leads to the entry of environmental pollutants and immune cells into the seminiferous tubules, resulting in adverse reproductive effects. Additionally, PS-MPs induce reproductive damage by generating oxidative stress, inflammation, autophagy, and alterations in the composition of intestinal flora. Despite these findings, the precise mechanism by which PS-MPs disrupt the BTB remains inconclusive, necessitating further investigation into the underlying processes. This review aims to enhance our understanding of the pernicious effects of PS-MP exposure on the BTB and explore potential mechanisms to offer novel perspectives on BTB damage caused by PS-MPs.


Assuntos
Barreira Hematotesticular , Microplásticos , Poliestirenos , Microplásticos/toxicidade , Poliestirenos/toxicidade , Masculino , Humanos , Barreira Hematotesticular/efeitos dos fármacos , Animais , Espermatogênese/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Poluentes Ambientais/toxicidade
5.
Environ Health Perspect ; 132(6): 67003, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38833407

RESUMO

BACKGROUND: Maternal exposure to environmental chemicals can cause adverse health effects in offspring. Mounting evidence supports that these effects are influenced, at least in part, by epigenetic modifications. It is unknown whether epigenetic changes in surrogate tissues such as the blood are reflective of similar changes in target tissues such as cortex or liver. OBJECTIVE: We examined tissue- and sex-specific changes in DNA methylation (DNAm) associated with human-relevant lead (Pb) and di(2-ethylhexyl) phthalate (DEHP) exposure during perinatal development in cerebral cortex, blood, and liver. METHODS: Female mice were exposed to human relevant doses of either Pb (32 ppm) via drinking water or DEHP (5mg/kg-day) via chow for 2 weeks prior to mating through offspring weaning. Whole genome bisulfite sequencing (WGBS) was utilized to examine DNAm changes in offspring cortex, blood, and liver at 5 months of age. Metilene and methylSig were used to identify differentially methylated regions (DMRs). Annotatr and ChIP-enrich were used for genomic annotations and gene set enrichment tests of DMRs, respectively. RESULTS: The cortex contained the majority of DMRs associated with Pb (66%) and DEHP (57%) exposure. The cortex also contained the greatest degree of overlap in DMR signatures between sexes (n=13 and 8 DMRs with Pb and DEHP exposure, respectively) and exposure types (n=55 and 39 DMRs in males and females, respectively). In all tissues, detected DMRs were preferentially found at genomic regions associated with gene expression regulation (e.g., CpG islands and shores, 5' UTRs, promoters, and exons). An analysis of GO terms associated with DMR-containing genes identified imprinted genes to be impacted by both Pb and DEHP exposure. Of these, Gnas and Grb10 contained DMRs across tissues, sexes, and exposures, with some signatures replicated between target and surrogate tissues. DMRs were enriched in the imprinting control regions (ICRs) of Gnas and Grb10, and we again observed a replication of DMR signatures between blood and target tissues. Specifically, we observed hypermethylation of the Grb10 ICR in both blood and liver of Pb-exposed male animals. CONCLUSIONS: These data provide preliminary evidence that imprinted genes may be viable candidates in the search for epigenetic biomarkers of toxicant exposure in target tissues. Additional research is needed on allele- and developmental stage-specific effects, as well as whether other imprinted genes provide additional examples of this relationship. https://doi.org/10.1289/EHP14074.


Assuntos
Metilação de DNA , Impressão Genômica , Chumbo , Fígado , Animais , Metilação de DNA/efeitos dos fármacos , Camundongos , Feminino , Fígado/efeitos dos fármacos , Masculino , Chumbo/toxicidade , Chumbo/sangue , Impressão Genômica/efeitos dos fármacos , Dietilexilftalato/toxicidade , Encéfalo/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Exposição Materna , Ácidos Ftálicos/toxicidade , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Epigênese Genética/efeitos dos fármacos
6.
Int J Mol Sci ; 25(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38732095

RESUMO

Phthalates are chemical compounds, mainly used as additives in plastics, which are known to induce harmful impacts to the environment and human health due to their ability to act as hormone-mimics. Few studies have been reported on the relationship between human exposure to phthalates and the level of circulating microRNAs (miRs), especially those miRs encapsulated in extracellular vesicles/exosomes or exosome-like vesicles (ELVs). We examined the relationship of ELV-miR expression patterns and urine of adult men with five phthalate metabolites (i.e., mono isobutyl phthalate, mono-n-butyl phthalate, mono benzyl phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, mono-(2-ethylhexyl) phthalate) to identify potential biomarkers and relevant pathways. We found significant positive associations which were further confirmed by multivariable analysis. Overall, our analyses showed that the Σ phthalate metabolite concentration was associated with a significant increase in the expression level of two miRs found in ELV: miR-202 and miR-543. Different pathways including cancer and immune-related responses were predicted to be involved in this relationship. Analyzing the specific downstream target genes of miR-202 and miR-543, we identified the phosphatase and tensin homolog (PTEN) as the key gene in several converging pathways. In summary, the obtained results demonstrate that exposure to environmental phthalates could be related to altered expression profiles of specific ELV-miRs in adult men, thereby demonstrating the potential of miRs carried by exosomes to act as early effect biomarkers.


Assuntos
Exossomos , Vesículas Extracelulares , MicroRNAs , Ácidos Ftálicos , Ácidos Ftálicos/urina , Ácidos Ftálicos/toxicidade , Humanos , Masculino , MicroRNAs/genética , MicroRNAs/urina , Exossomos/genética , Exossomos/metabolismo , Adulto , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/genética , Biomarcadores/urina , Exposição Ambiental/efeitos adversos , Pessoa de Meia-Idade , Poluentes Ambientais/urina , Poluentes Ambientais/toxicidade
7.
Sci Total Environ ; 931: 172938, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38703850

RESUMO

Cadmium (Cd) is a widely distributed typical environmental pollutant and one of the most toxic heavy metals. It is well-known that environmental Cd causes testicular damage by inducing classic types of cell death such as cell apoptosis and necrosis. However, as a new type of cell death, the role and mechanism of pyroptosis in Cd-induced testicular injury remain unclear. In the current study, we used environmental Cd to generate a murine model with testicular injury and AIM2-dependent pyroptosis. Based on the model, we found that increased cytoplasmic mitochondrial DNA (mtDNA), activated mitochondrial proteostasis stress occurred in Cd-exposed testes. We used ethidium bromide to generate mtDNA-deficient testicular germ cells and further confirmed that increased cytoplasmic mtDNA promoted AIM2-dependent pyroptosis in Cd-exposed cells. Uracil-DNA glycosylase UNG1 overexpression indicated that environmental Cd blocked UNG-dependent repairment of damaged mtDNA to drive the process in which mtDNA releases to cytoplasm in the cells. Interestingly, we found that environmental Cd activated mitochondrial proteostasis stress by up-regulating protein expression of LONP1 in testes. Testicular specific LONP1-knockdown significantly reversed Cd-induced UNG1 protein degradation and AIM2-dependent pyroptosis in mouse testes. In addition, environmental Cd significantly enhanced the m6A modification of Lonp1 mRNA and its stability in testicular germ cells. Knockdown of IGF2BP1, a reader of m6A modification, reversed Cd-induced upregulation of LONP1 protein expression and pyroptosis activation in testicular germ cells. Collectively, environmental Cd induces m6A modification of Lonp1 mRNA to activate mitochondrial proteostasis stress, increase cytoplasmic mtDNA content, and trigger AIM2-dependent pyroptosis in mouse testes. These findings suggest that mitochondrial proteostasis stress is a potential target for the prevention of testicular injury.


Assuntos
Cádmio , Mitocôndrias , Piroptose , Testículo , Animais , Cádmio/toxicidade , Masculino , Camundongos , Testículo/efeitos dos fármacos , Testículo/metabolismo , Piroptose/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Proteostase , Proteínas Mitocondriais/metabolismo , Exposição Ambiental/efeitos adversos , DNA Mitocondrial , Proteases Dependentes de ATP/metabolismo , Estresse Proteotóxico
8.
Chemosphere ; 358: 142275, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38719125

RESUMO

Microplastics (MPs) are widespread environmental contaminants that have been detected in animals and humans. However, their toxic effects on terrestrial mammals and the underlying mechanisms are still not well understood. Herein, we explored the role of gut microbiota in mediating the toxicity of micro- and nano-sized polystyrene plastics (PS-MPs/PS-NPs) using an antibiotic depleted mice model. The results showed that PS-MPs and PS-NPs exposure disrupted the composition and structure of the gut microbiota. Specifically, these particles led to an increase in pathogenic Esherichia-shigella, while depleting probiotics such as Akkermansia and Lactobacillus. Comparatively, PS-NPs particles had more pronounced effect, leading to obviously shifted the colon transcriptional profiles characterized by inducing the enrichment of colon metabolism and immune-related pathways (i.e., upregulated in genes like udgh, ugt1a1, ugt1a6a, ugt1a7c and ugt2b34). Additionally, both PS-MPs and PS-NPs induced oxidative stress, gut-liver damage and systemic inflammation in mice. Mechanistically, we confirmed that PS particles disturbed gut microbiota, activating TLR2-My88-NF-κB pathway to trigger the release of inflammatory cytokine IL-1ß and TNF-α. The damage and inflammation caused by both size of PS particles was alleviated when the gut microbiota was depleted. In conclusion, our findings deepen the understanding of the molecule mechanisms by which gut microbiota mediate the toxicity of PS particles, informing health implications of MPs pollution.


Assuntos
Microbioma Gastrointestinal , Microplásticos , Poliestirenos , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Poliestirenos/toxicidade , Camundongos , Microplásticos/toxicidade , Nanopartículas/toxicidade , Nanopartículas/química , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Inflamação/induzido quimicamente , Poluentes Ambientais/toxicidade , Masculino , NF-kappa B/metabolismo
9.
J Immunotoxicol ; 21(1): 2343362, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38712868

RESUMO

Per- and polyfluoroalkyl substances (PFASs) are a large class of compounds used in a variety of processes and consumer products. Their unique chemical properties make them ubiquitous and persistent environmental contaminants while also making them economically viable and socially convenient. To date, several reviews have been published to synthesize information regarding the immunotoxic effects of PFASs on the adaptive immune system. However, these reviews often do not include data on the impact of these compounds on innate immunity. Here, current literature is reviewed to identify and incorporate data regarding the effects of PFASs on innate immunity in humans, experimental models, and wildlife. Known mechanisms by which PFASs modulate innate immune function are also reviewed, including disruption of cell signaling, metabolism, and tissue-level effects. For PFASs where innate immune data are available, results are equivocal, raising additional questions about common mechanisms or pathways of toxicity, but highlighting that the innate immune system within several species can be perturbed by exposure to PFASs. Recommendations are provided for future research to inform hazard identification, risk assessment, and risk management practices for PFASs to protect the immune systems of exposed organisms as well as environmental health.


Assuntos
Poluentes Ambientais , Fluorocarbonos , Imunidade Inata , Imunidade Inata/efeitos dos fármacos , Humanos , Animais , Fluorocarbonos/efeitos adversos , Fluorocarbonos/toxicidade , Poluentes Ambientais/toxicidade , Poluentes Ambientais/efeitos adversos , Exposição Ambiental/efeitos adversos
10.
Int J Mol Sci ; 25(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38731818

RESUMO

Early life exposure lays the groundwork for the risk of developing cardiovascular-kidney-metabolic (CKM) syndrome in adulthood. Various environmental chemicals to which pregnant mothers are commonly exposed can disrupt fetal programming, leading to a wide range of CKM phenotypes. The aryl hydrocarbon receptor (AHR) has a key role as a ligand-activated transcription factor in sensing these environmental chemicals. Activating AHR through exposure to environmental chemicals has been documented for its adverse impacts on cardiovascular diseases, hypertension, diabetes, obesity, kidney disease, and non-alcoholic fatty liver disease, as evidenced by both epidemiological and animal studies. In this review, we compile current human evidence and findings from animal models that support the connection between antenatal chemical exposures and CKM programming, focusing particularly on AHR signaling. Additionally, we explore potential AHR modulators aimed at preventing CKM syndrome. As the pioneering review to present evidence advocating for the avoidance of toxic chemical exposure during pregnancy and deepening our understanding of AHR signaling, this has the potential to mitigate the global burden of CKM syndrome in the future.


Assuntos
Doenças Cardiovasculares , Efeitos Tardios da Exposição Pré-Natal , Receptores de Hidrocarboneto Arílico , Receptores de Hidrocarboneto Arílico/metabolismo , Receptores de Hidrocarboneto Arílico/genética , Humanos , Gravidez , Animais , Feminino , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/induzido quimicamente , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Nefropatias/etiologia , Exposição Materna/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Rim/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Desenvolvimento Fetal/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Poluentes Ambientais/efeitos adversos , Reprogramação Metabólica
11.
J Toxicol Sci ; 49(5): 209-218, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38692908

RESUMO

The immune system is sensitive to many chemicals. Among dioxin compounds, 2,3,7,8-tetrachlorodizenzo-p-dioxin (TCDD) is the most toxic environmental pollutant. The effects of perinatal maternal exposure to dioxins may persist into childhood. However, there have been no reports to date on the effects of exposure to dioxins during infancy, when the immune organs are developing. Therefore, we investigated the effects of TCDD and antigen exposure during lactation on immune function, especially antibody production capacity, in adult mice. Beginning the day after delivery, lactating mothers were orally administered TCDD or a mixture of TCDD and ovalbumin (OVA) daily for 4 weeks, until the pups were weaned. At 6 weeks of age, progeny mice were orally administered OVA daily for 10 weeks, while non-progeny mice were orally administered OVA or a mixture of TCDD and OVA daily for 10 weeks. Production of serum OVA-specific IgG was examined weekly. The amount of TCDD transferred from the mother to the progeny via breast milk was determined by measuring TCDD in the gastric contents of the progeny. A trend toward increasing IgA titer was observed in TCDD-treated mice, and production of IgE was observed only in progeny whose mothers were treated with TCDD and OVA. The results suggest that exposure to TCDD and OVA in breast milk can affect immune function in newborns.


Assuntos
Lactação , Ovalbumina , Dibenzodioxinas Policloradas , Animais , Feminino , Ovalbumina/imunologia , Ovalbumina/administração & dosagem , Dibenzodioxinas Policloradas/toxicidade , Exposição Materna/efeitos adversos , Formação de Anticorpos/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Imunoglobulina G/sangue , Imunoglobulina A/sangue , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Antígenos/imunologia , Camundongos , Gravidez , Leite/imunologia , Masculino , Leite Humano/imunologia , Administração Oral
12.
Environ Health Perspect ; 132(5): 57001, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38701112

RESUMO

BACKGROUND: Disruptions in vascular formation attributable to chemical insults is a pivotal risk factor or potential etiology of developmental defects and various disease settings. Among the thousands of chemicals threatening human health, the highly concerning groups prevalent in the environment and detected in biological monitoring in the general population ought to be prioritized because of their high exposure risks. However, the impacts of a large number of environmental chemicals on vasculature are far from understood. The angioarchitecture complexity and technical limitations make it challenging to analyze the entire vasculature efficiently and identify subtle changes through a high-throughput in vivo assay. OBJECTIVES: We aimed to develop an automated morphometric approach for the vascular profile and assess the vascular morphology of health-concerning environmental chemicals. METHODS: High-resolution images of the entire vasculature in Tg(fli1a:eGFP) zebrafish were collected using a high-content imaging platform. We established a deep learning-based quantitative framework, ECA-ResXUnet, combined with MATLAB to segment the vascular networks and extract features. Vessel scores based on the rates of morphological changes were calculated to rank vascular toxicity. Potential biomarkers were identified by vessel-endothelium-gene-disease integrative analysis. RESULTS: Whole-trunk blood vessels and the cerebral vasculature in larvae exposed to 150 representative chemicals were automatically segmented as comparable to human-level accuracy, with sensitivity and specificity of 95.56% and 95.81%, respectively. Chemical treatments led to heterogeneous vascular patterns manifested by 31 architecture indexes, and the common cardinal vein (CCV) was the most affected vessel. The antipsychotic medicine haloperidol, flame retardant 2,2-bis(chloromethyl)trimethylenebis[bis(2-chloroethyl) phosphate], and tert-butylphenyl diphenyl phosphate ranked as the top three in vessel scores. Pesticides accounted for the largest group, with a vessel score of ≥1, characterized by a remarkable inhibition of subintestinal venous plexus and delayed development of CCV. Multiple-concentration evaluation of nine per- and polyfluoroalkyl substances (PFAS) indicated a low-concentration effect on vascular impairment and a positive association between carbon chain length and benchmark concentration. Target vessel-directed single-cell RNA sequencing of fli1a+ cells from larvae treated with λ-cyhalothrin, perfluorohexanesulfonic acid, or benzylbutyl phthalate, along with vessel-endothelium-gene-disease integrative analysis, uncovered potential associations with vascular disorders and identified biomarker candidates. DISCUSSION: This study provides a novel paradigm for phenotype-driven screenings of vascular-disrupting chemicals by converging morphological and transcriptomic profiles at a high-resolution level, serving as a powerful tool for large-scale toxicity tests. Our approach and the high-quality morphometric data facilitate the precise evaluation of vascular effects caused by environmental chemicals. https://doi.org/10.1289/EHP13214.


Assuntos
Peixe-Zebra , Animais , Poluentes Ambientais/toxicidade , Vasos Sanguíneos/efeitos dos fármacos
13.
Environ Geochem Health ; 46(6): 197, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38696118

RESUMO

Micro/nanoplastics (MNPs) are emerging as environmental pollutants with potential threats to human health. The accumulation of MNPs in the body can cause oxidative stress and increase the risk of cardiovascular disease (CVD). With the aim to systematically evaluate the extent of MNPs-induced oxidative damage and serum biochemical parameters in rats and mice, a total of 36 eligible articles were included in this meta-analysis study. The results reported that MNPs can significantly increase the levels of oxidants such as reactive oxygen species (ROS) and malondialdehyde (MDA) (P < 0.05), and resulted in notable increase in serum biochemical parameters including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (P < 0.05). Conversely, MNPs significantly reduced levels of antioxidants such as superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx) and catalase (CAT) (P < 0.05). Subgroup analysis revealed that smaller MNPs with oral administration and prolonged treatment, were associated with more pronounced oxidative stress and enhanced serum biochemical parameters alteration. In addition, after affected by MNPs, the levels of ALT and AST in liver group (SMD = 2.26, 95% CI = [1.59, 2.94] and SMD = 3.10, 95% CI = [1.25, 4.94]) were higher than those in other organs. These comprehensive results provide a scientific foundation for devising strategies to prevent MNPs-induced damage, contributing to solution of this environmental and health challenge.


Assuntos
Estresse Oxidativo , Animais , Estresse Oxidativo/efeitos dos fármacos , Ratos , Camundongos , Aspartato Aminotransferases/sangue , Microplásticos/toxicidade , Alanina Transaminase/sangue , Antioxidantes/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Poluentes Ambientais/toxicidade , Nanopartículas , Malondialdeído/sangue , Superóxido Dismutase/metabolismo
14.
Front Immunol ; 15: 1333563, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38807590

RESUMO

Breast cancer stands as the most prevalent form of cancer among women globally, influenced by a combination of genetic and environmental factors. Recent studies have investigated changes in microRNAs (miRNAs) during breast cancer progression and the potential impact of environmental chemicals on miRNA expression. This review aims to provide an updated overview of miRNA alterations in breast cancer and to explore their potential association with environmental chemicals. We will discuss the current knowledge on dysregulated miRNAs in breast cancer, including both upregulated and downregulated miRNAs. Additionally, we will review the influence of environmental chemicals, such as endocrine-disrupting compounds, heavy metals, and air pollutants, on miRNA expression and their potential contribution to breast cancer development. This review aims to advance our understanding of the complex molecular mechanisms underlying miRNA dysregulation in breast cancer by comprehensively examining miRNA alterations and their association with environmental chemicals. This knowledge is crucial for the development of targeted therapies and preventive measures. Furthermore, identifying specific miRNAs affected by environmental chemicals may allow the prediction of individual susceptibility to breast cancer and the design of personalized intervention strategies.


Assuntos
Neoplasias da Mama , Regulação Neoplásica da Expressão Gênica , MicroRNAs , Humanos , MicroRNAs/genética , Neoplasias da Mama/genética , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/etiologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Poluentes Ambientais/efeitos adversos , Exposição Ambiental/efeitos adversos , Animais , Disruptores Endócrinos/efeitos adversos
15.
Ecotoxicol Environ Saf ; 279: 116505, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38810287

RESUMO

Micro(nano)plastics (MNPs) have been detected in various ecological environments and are widely used due to their stable properties, raising widespread concern about their potential human reproductive toxicity. Currently, infertility affects approximately 10-30% of couples of reproductive age globally. MNPs, as environmental pollutants, have been shown to exhibit reproductive toxicity through intrinsic mechanisms or as carriers of other hazardous substances. Numerous studies have established that MNPs of varying sizes and types can penetrate biological barriers, and enter tissues and even organelles of organisms through four main routes: dietary ingestion, inhalation, dermal contact, and medical interventions. However, historical research on the toxic effects of MNPs on reproduction mainly focused on lower and aquatic species. We conducted an inclusive review of studies involving terrestrial mammals, revealing that MNPs can induce reproductive toxicity via various mechanisms such as oxidative stress, inflammation, fibrosis, apoptosis, autophagy, disruption of intestinal flora, endocrine disruption, endoplasmic reticulum stress, and DNA damage. In terrestrial mammals, reproductive toxicity predominantly manifests as disruption in the blood-testis barrier (BTB), impaired spermatogenesis, sperm malformation, sperm DNA damage, reduced sperm fertilizing capacity, compromised oocyte maturation, impaired follicular growth, granulosa cell apoptosis, diminished ovarian reserve function, uterine and ovarian fibrosis, and endocrine disruption, among other effects. Furthermore, MNPs can traverse the maternal-fetal interface, potentially impacting offspring reproductive health. To gain a comprehensive understanding of the potential reproductive toxicity and underlying mechanisms of MNPs with different sizes, polymer types, shapes, and carried toxins, as well as to explore effective protective interventions for mitigating reproductive damage, further in-depth animal studies, clinical trials, and large-scale epidemiological studies are urgently required.


Assuntos
Mamíferos , Reprodução , Animais , Reprodução/efeitos dos fármacos , Feminino , Masculino , Humanos , Microplásticos/toxicidade , Poluentes Ambientais/toxicidade , Estresse Oxidativo/efeitos dos fármacos
16.
Toxicology ; 505: 153844, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38801937

RESUMO

Tributyltin chloride (TBTC) is a ubiquitous environmental pollutant with various adverse effects on human health. Exosomes are cell - derived signaling and substance transport vesicles. This investigation aimed to explore whether exosomes could impact the toxic effects caused by TBTC via their transport function. Cytotoxicity, DNA and chromosome damage caused by TBTC on MCF-7 cells were analyzed with CCK-8, flow cytometry, comet assay and micronucleus tests, respectively. Exosomal characterization and quantitative analysis were performed with ultracentrifugation, transmission electron microscope (TEM) and bicinchoninic acid (BCA) methods. TBTC content in exosomes was detected with Liquid Chromatography-Mass Spectrometry (LC-MS). The impacts of exosomal secretion on the toxic effects of TBTC were analyzed. Our data indicated that TBTC caused significant cytotoxicity, DNA and chromosome damage effects on MCF-7 cells, and a significantly increased exosomal secretion. Importantly, TBTC could be transported out of MCF-7 cells by exosomes. Further, when exosomal secretion was blocked with GW4869, the toxic effects of TBTC were significantly exacerbated. We concluded that TBTC promoted exosomal secretion, which in turn transported TBTC out of the source cells to alleviate its toxic effects. This investigation provided a novel insight into the role and mechanism of exosomal release under TBTC stress.


Assuntos
Dano ao DNA , Exossomos , Compostos de Trialquitina , Humanos , Exossomos/efeitos dos fármacos , Exossomos/metabolismo , Compostos de Trialquitina/toxicidade , Células MCF-7 , Dano ao DNA/efeitos dos fármacos , Transporte Biológico/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Sobrevivência Celular/efeitos dos fármacos
17.
Cells ; 13(10)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38786027

RESUMO

Recent evidence indicates that exposure to environmental toxins, both short-term and long-term, can increase the risk of developing neurological disorders, including neurodegenerative diseases (i.e., Alzheimer's disease and other dementias) and acute brain injury (i.e., stroke). For stroke, the latest systematic analysis revealed that exposure to ambient particulate matter is the second most frequent stroke risk after high blood pressure. However, preclinical and clinical stroke investigations on the deleterious consequences of environmental pollutants are scarce. This review examines recent evidence of how environmental toxins, absorbed along the digestive tract or inhaled through the lungs, affect the host cellular response. We particularly address the consequences of environmental toxins on the immune response and the microbiome at the gut and lung barrier sites. Additionally, this review highlights findings showing the potential contribution of environmental toxins to an increased risk of stroke. A better understanding of the biological mechanisms underlying exposure to environmental toxins has the potential to mitigate stroke risk and other neurological disorders.


Assuntos
Encéfalo , Exposição Ambiental , Pulmão , Acidente Vascular Cerebral , Humanos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/toxicidade , Poluentes Ambientais/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Eixo Encéfalo-Intestino , Fatores de Risco
18.
Ecotoxicol Environ Saf ; 278: 116409, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38701656

RESUMO

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.


Assuntos
7,8-Di-Hidro-7,8-Di-Hidroxibenzo(a)pireno 9,10-óxido , Benzo(a)pireno , Movimento Celular , Regulação para Baixo , Trofoblastos , Trofoblastos/efeitos dos fármacos , Feminino , Animais , Movimento Celular/efeitos dos fármacos , Benzo(a)pireno/toxicidade , Humanos , Camundongos , 7,8-Di-Hidro-7,8-Di-Hidroxibenzo(a)pireno 9,10-óxido/toxicidade , Gravidez , Disruptores Endócrinos/toxicidade , Poluentes Ambientais/toxicidade , Linhagem Celular , Aborto Espontâneo/induzido quimicamente
19.
Ecotoxicol Environ Saf ; 278: 116390, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38705037

RESUMO

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.


Assuntos
Benzo(a)pireno , Fígado , Microplásticos , Estresse Oxidativo , Poliestirenos , Ratos Sprague-Dawley , Animais , Estresse Oxidativo/efeitos dos fármacos , Benzo(a)pireno/toxicidade , Microplásticos/toxicidade , Masculino , Poliestirenos/toxicidade , Fígado/efeitos dos fármacos , Fígado/patologia , Ratos , Poluentes Ambientais/toxicidade , Antioxidantes/metabolismo , NF-kappa B/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo
20.
Ecotoxicol Environ Saf ; 278: 116393, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38714083

RESUMO

Micro(nano)plastic, as a new type of environmental pollutant, have become a potential threat to the life and health of various stages of biology. However, it is not yet clear whether they will affect brain development in the fetal stage. Therefore, this study aims to explore the potential effects of nanoplastics on the development of fetal rat brains. To assess the allocation of NPs (25 nm and 50 nm) in various regions of the fetal brain, pregnant rats were exposed to concentrations (50, 10, 2.5, and 0.5 mg/kg) of PS-NPs. Our results provided evidence of the transplacental transfer of PS-NPs to the fetal brain, with a prominent presence observed in several cerebral regions, notably the cerebellum, hippocampus, striatum, and prefrontal cortex. This distribution bias might be linked to the developmental sequence of each brain region. Additionally, we explored the influence of prenatal exposure on the myelin development of the cerebellum, given its the highest PS-NP accumulation in offspring. Compared with control rats, PS-NPs exposure caused a significant reduction in myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) expression, a decrease in myelin thickness, an increase in cell apoptosis, and a decline in the oligodendrocyte population. These effects gave rise to motor deficits. In conclusion, our results identified the specific distribution of NPs in the fetal brain following prenatal exposure and revealed that prenatal exposure to PS-NPs can suppress myelin formation in the cerebellum of the fetus.


Assuntos
Encéfalo , Bainha de Mielina , Poliestirenos , Animais , Feminino , Gravidez , Encéfalo/efeitos dos fármacos , Encéfalo/embriologia , Encéfalo/metabolismo , Bainha de Mielina/efeitos dos fármacos , Bainha de Mielina/metabolismo , Ratos , Poliestirenos/toxicidade , Poluentes Ambientais/toxicidade , Proteína Básica da Mielina/metabolismo , Exposição Materna , Nanopartículas/toxicidade , Apoptose/efeitos dos fármacos , Microplásticos/toxicidade , Ratos Sprague-Dawley , Troca Materno-Fetal , Feto/efeitos dos fármacos
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