RESUMO
Population studies reveal widespread exposure to phthalates. Understanding their absorption, distribution, metabolism, and excretion is vital to reduce exposure. However, data on skin absorption remain limited. We thus aim to characterize the skin permeation of three phthalates in a mixture, neat or in emulsion; di(2-ethylhexyl) phthalate (d4-DEHP), dibutyl phthalate (d4-DBP), and diethyl phthalate (d4-DEP), by comparing in vitro human skin (800⯵m) permeation (24â¯hours) results using flow-through diffusion cells with urine results obtained from volunteers exposed to the same mixture applied to a forearm (40â¯cm2). Metabolites were analyzed in receptor fluids and urine. Phthalates crossed the skin barrier and metabolized into monoesters before elimination. Increased permeation was observed for phthalates in emulsion compared to neat substances, with polyethylene glycol (PEG) in the receptor fluid enhancing emulsion permeation, but not affecting neat substances. In vitro results mirrored in vivo findings: DEP showed rapid permeation (J: â¼2â¯ug/cm2/h) and urinary excretion peaking at six hours post-application, whereas DBP exhibited slower kinetics (J: â¼0.1â¯ug/cm2/h), with a urinary peak at 15-17â¯hours post-application. DEHP had minimal permeation (J: â¼0.0002â¯ug/cm2/h) with no observable urinary peak. These findings underscore the importance of comprehending phthalate skin absorption for effective exposure mitigation strategies.
Assuntos
Dibutilftalato , Ácidos Ftálicos , Absorção Cutânea , Pele , Humanos , Ácidos Ftálicos/farmacocinética , Ácidos Ftálicos/urina , Ácidos Ftálicos/metabolismo , Adulto , Masculino , Dibutilftalato/farmacocinética , Dibutilftalato/urina , Dibutilftalato/metabolismo , Pele/metabolismo , Feminino , Dietilexilftalato/farmacocinética , Dietilexilftalato/metabolismo , Dietilexilftalato/urina , Adulto Jovem , Pessoa de Meia-Idade , Administração Cutânea , EmulsõesRESUMO
The concerning of plastic pollution in different ecosystems has been worsened by the widespread presence. Phthalate esters (PAEs), plasticizers found in everyday products, can migrate into the environment, especially into the oceans. Researches on their effects on cetaceans are still rare. Metabolomics helps assess perturbations induced by exposure to PAEs, which act as persistent endocrine disruptors. Four PAEs (dimethyl phthalate - DMP, diethyl phthalate - DEP, dibutyl phthalate - DBP, and di(2-ethylhexyl phthalate - DEHP) were analyzed, along with cholesterol and fatty acid profiles of P. blainvillei's blubber samples collected in southern Brazil. The study reveals pervasive contamination by PAEs - especially DEHP, present in all samples - with positive correlations between DEP content and animal size and weight, as well as between the DEHP amount and the C17:1 fatty acid. These findings will be relevant to conservation efforts aimed at this threatened species and overall marine ecosystems.
Assuntos
Golfinhos , Monitoramento Ambiental , Ésteres , Metaboloma , Ácidos Ftálicos , Poluentes Químicos da Água , Animais , Brasil , Ácidos Ftálicos/metabolismo , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/análise , Ésteres/análise , Ésteres/metabolismo , Golfinhos/metabolismo , Tecido Adiposo/metabolismo , Dietilexilftalato/metabolismo , Plastificantes , Disruptores Endócrinos/análise , Masculino , Feminino , DibutilftalatoRESUMO
Phthalate esters (PAEs), as a major plasticizer with multi-biotoxicity, are frequently detected in marine environments, and potentially affecting the survival of aquatic organisms. In the study, three typical PAEs (dimethyl phthalate [DMP], dibutyl phthalate [DBP] and di(2-ethylhexyl) phthalate [DEHP]) were selected to investigate the accumulation patterns and ecotoxicological effects on Mytilus coruscus (M. coruscus). In M. coruscus, the accumulation was DEHP>DBP>DMP, and the bioaccumulation in tissues was digestive glands>gills>gonads>muscles. Meanwhile, the activities of superoxide dismutase (SOD) and catalase (CAT) showed an activation-decrease-activation trend of stress, with more pronounced concentration effects. Glutathione reductase (GSH) activity was significantly increased, and its expression was more sensitive to be induced at an early stage. The metabolic profiles of the gonads, digestive glands and muscle tissues were significantly altered, and DEHP had a greater effect on the metabolic profiles of M. coruscus, with the strongest interference. PAEs stress for 7 d significantly altered the volatile components of M. coruscus, with potential implications for their nutritional value. This study provides a biochemical, metabolomic, and nutritional analysis of DMP, DBP, and DEHP toxic effects on M. coruscus from a multidimensional perspective, which provides support for ecotoxicological studies of PAEs on marine organisms. ENVIRONMENTAL IMPLICATION: Phthalate esters (PAEs), synthetic compounds from phthalic acid, are widespread in the environment, household products, aquatic plants, animals, and crops, posing a significant threat to human health. However, the majority of toxicological studies examining the effects of PAEs on aquatic organisms primarily focus on non-economic model organisms like algae and zebrafish. Relatively fewer studies have been conducted on marine organisms, particularly economically important shellfish. So, this study is innovative and necessary. This study provides a biochemical, metabolomic, and nutritional analysis of DMP, DBP, and DEHP toxic effects on mussels, and supports the ecotoxicology of PAEs on marine organisms.
Assuntos
Mytilus , Ácidos Ftálicos , Plastificantes , Poluentes Químicos da Água , Animais , Ácidos Ftálicos/toxicidade , Ácidos Ftálicos/metabolismo , Mytilus/efeitos dos fármacos , Mytilus/metabolismo , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/metabolismo , Plastificantes/toxicidade , Plastificantes/metabolismo , Superóxido Dismutase/metabolismo , Antioxidantes/metabolismo , Dietilexilftalato/toxicidade , Dietilexilftalato/metabolismo , Catalase/metabolismo , Dibutilftalato/toxicidade , Dibutilftalato/metabolismo , Glutationa Redutase/metabolismo , Gônadas/efeitos dos fármacos , Gônadas/metabolismo , Ésteres/metabolismo , Ésteres/toxicidade , Estresse Oxidativo/efeitos dos fármacosRESUMO
Because of the significant environmental and health hazards imposed by di(2-ethylhexyl) phthalate (DEHP), a common plasticizer, developing safe and green techniques to degrade DEHP plasticizer is of huge scientific significance. It has been observed that environmental contamination of DEHP may also induce serious food safety problems because crops raised in plasticizers contaminated soils would transfer the plasticizer into foods, such as Baijiu. Additionally, when plastic packaging or vessels are used during Baijiu fermentation and processing, plasticizer compounds frequently migrate and contaminate the product. In this study, hairpin-like structured peptides with catalytically active sites containing serine, histidine and aspartic acid were found to degrade DEHP. Furthermore, after incorporating caffeic acid molecules at the N-terminus, the peptides could be attached onto foam titanium (Ti) surfaces via enediol-metal interactions to create an enzyme-mimicking flow reactor for the degradation of DEHP in Baijiu. The structure and catalytic activity of peptides, their interaction with DEHP substrate and the hydrolysis mechanism of DEHP were discussed in this work. The stability and reusability of the peptide-modified foam Ti flow reactor were also investigated. This approach provides an effective technique for the degradation of plasticizer compounds.
Assuntos
Dietilexilftalato , Peptídeos , Plastificantes , Titânio , Dietilexilftalato/química , Dietilexilftalato/metabolismo , Plastificantes/química , Titânio/química , Peptídeos/química , Peptídeos/metabolismo , HidróliseRESUMO
Di (2-ethylhexyl) phthalate (DEHP), a toxic phthalate ester (PAE) plasticizer, is often detected in marine sediment and biota. Our understanding of DEHP-degrading marine bacteria and the associated genetic mechanisms is limited. This study established a synthetic bacterial consortium (A02) consisting of three marine bacteria (OR05, OR16, and OR21). Consortium A02 outperformed the individual strains in DEHP degradation. Investigations into the degradation of DEHP intermediates revealed that OR05 and OR16 likely contributed to enhanced DEHP degradation by Consortium A02 via the utilization of DEHP intermediates, such as protocatechuic acid and mono (ethylhexyl) phthalate, with OR21 as the key DEHP degrader. A pathway of DEHP degradation by Consortium A02 was predicted based on genome analysis and experimental degradation. Bioaugmentation with Consortium A02 led to 80% DEHP degradation in 26 days in saline sediment (100 mg/kg), surpassing the 53% degradation by indigenous microbes, indicating the potential of A02 for treating DEHP-contaminated sediments. Meanwhile, bioaugmentation notably changed the bacterial community, with the exclusive presence of certain bacterial genera in the A02 bioaugmented microcosms, and was predicted to result in a more dynamic and active sediment bacterial community. This study contributes to the limited literature on DEHP degradation by marine bacteria and their associated genes.
Assuntos
Bactérias , Biodegradação Ambiental , Dietilexilftalato , Sedimentos Geológicos , Consórcios Microbianos , Poluentes Químicos da Água , Sedimentos Geológicos/microbiologia , Dietilexilftalato/metabolismo , Bactérias/metabolismo , Bactérias/genética , Consórcios Microbianos/genética , Poluentes Químicos da Água/metabolismo , Plastificantes/metabolismo , Genoma BacterianoRESUMO
Selecting and cultivating low-accumulating crop varieties (LACVs) is the most effective strategy for the safe utilization of di-(2-ethylhexyl) phthalate (DEHP)-contaminated soils, promoting cleaner agricultural production. However, the adsorption-absorption-translocation mechanisms of DEHP along the root-shoot axis remains a formidable challenge to be solved, especially for the research and application of LACV, which are rarely reported. Here, systematic analyses of the root surface ad/desorption, root apexes longitudinal allocation, uptake and translocation pathway of DEHP in LACV were investigated compared with those in a high-accumulating crop variety (HACV) in terms of the root-shoot axis. Results indicated that DEHP adsorption was enhanced in HACV by root properties, elemental composition and functional groups, but the desorption of DEHP was greater in LACV than HACV. The migration of DEHP across the root surface was controlled by the longitudinal partitioning process mediated by root tips, where more DEHP accumulated in the root cap and meristem of LACV due to greater cell proliferation. Furthermore, the longitudinal translocation of DEHP in LACV was reduced, as evidenced by an increased proportion of DEHP in the root apoplast. The symplastic uptake and xylem translocation of DEHP were suppressed more effectively in LACV than HACV, because DEHP translocation in LACV required more energy, binding sites and transpiration. These results revealed the multifaceted regulation of DEHP accumulation in different choysum (Brassica parachinensis L.) varieties and quantified the pivotal regulatory processes integral to LACV formation.
Assuntos
Raízes de Plantas , Poluentes do Solo , Verduras , Raízes de Plantas/metabolismo , Poluentes do Solo/metabolismo , Poluentes do Solo/análise , Verduras/metabolismo , Solo/química , Ácidos Ftálicos/metabolismo , Dietilexilftalato/metabolismo , AdsorçãoRESUMO
BACKGROUND: Phthalates are widely used plasticizers, which were identified as risk factors in the development of many human diseases. However, the effects of phthalates in the periodontitis are unknown. We aimed to investigated the relationship of periodontitis and phthalate exposure as well as the underlying mechanisms. MATERIALS AND METHODS: Univariate and multivariate logistic regressions were employed to evaluate the association between phthalate metabolites and periodontitis. The generalized additive model and piecewise logistic regression were conducted to investigate the dose-response relationship. Cell and animal models were used to explore the role and mechanism of DEHP in the development of periodontitis. Transcriptome sequencing, bioinformatics analysis, western blot, immunofluorescence and mice model of periodontitis were also employed. RESULTS: MEHP (OR 1.14, 95% CI 1.05-1.24), MCPP (OR 1.08, 95% CI 1.00-1.17), MEHHP (OR 1.18, 95% CI 1.08-1.29), MEOHP (OR 1.18, 95% CI 1.07-1.29), MiBP (OR 1.15, 95% CI 1.04-1.28), and MECPP (OR 1.20, 95% CI 1.09-1.32) were independent risk factors. And MEHHP, the metabolite of DEHP, showed the relative most important effects on periodontitis with the highest weight (0.34) among all risk factors assessed. And the increase of inflammation and the activation of NFκB pathway in the periodontitis model mice and cells were observed. CONCLUSION: Exposure to multiple phthalates was positively associated with periodontitis in US adults between 30 and 80 years old. And DEHP aggravated inflammation in periodontitis by activating NFκB pathway.
Assuntos
Dietilexilftalato , Poluentes Ambientais , Periodontite , Ácidos Ftálicos , Adulto , Humanos , Animais , Camundongos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Exposição Ambiental/análise , Dietilexilftalato/metabolismo , Ácidos Ftálicos/toxicidade , Ácidos Ftálicos/metabolismo , Periodontite/induzido quimicamente , Inflamação , Poluentes Ambientais/análiseRESUMO
Epidemiological studies have demonstrated the embryonic and developmental toxicity of plasticizers. Thus, understanding the in utero biotransformation and accumulation of plasticizers is essential to assessing their fate and potential toxicity in early life. In the present study, 311 infant hair samples and 271 paired meconium samples were collected at birth in Guangzhou, China, to characterize fetal exposure to legacy and emerging plasticizers and their metabolites. Results showed that most of the target plasticizers were detected in infant hair, with medians of 9.30, 27.6, and 0.145 ng/g for phthalate esters (PAEs), organic phosphate ester (OPEs), and alternative plasticizers (APs), and 1.44, 0.313, and 0.066 ng/g for the metabolites of PAEs, OPEs, and APs, respectively. Positive correlations between plasticizers and their corresponding primary metabolites, as well as correlations among the oxidative metabolites of bis(2-ethylhexyl) phthalate (DEHP) and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), were observed, indicating that infant hair retained the major phase-I metabolism of the target plasticizers. While no positive correlations were found in parent compounds or their primary metabolites between paired infant hair and meconium, significant positive correlations were observed among secondary oxidative metabolites of DEHP and DINCH in hair and meconium, suggesting that the primary metabolites in meconium come from hydrolysis of plasticizers in the fetus but most of the oxidative metabolites come from maternal-fetal transmission. The parent compound/metabolite ratios in infant hair showed a decreasing trend across pregnancy, suggesting in utero accumulation and deposition of plasticizers. To the best of our knowledge, this study is the first to report in utero exposure to both parent compounds and metabolites of plasticizers by using paired infant hair and meconium as noninvasive biomonitoring matrices and provides novel insights into the fetal biotransformation and accumulation of plasticizers across pregnancy.
Assuntos
Dietilexilftalato , Ácidos Ftálicos , Humanos , Gravidez , Recém-Nascido , Feminino , Plastificantes , Mecônio/metabolismo , Dietilexilftalato/metabolismo , Dietilexilftalato/toxicidade , Ácidos Ftálicos/metabolismo , Cabelo/metabolismo , Organofosfatos , Biotransformação , Ésteres/metabolismo , Exposição Ambiental/análiseRESUMO
Phthalates, classified as environmental endocrine disruptors, pose potential toxicity risks to human health. Metabolic dysfunction-associated fatty liver disease is one of the most widespread liver diseases globally. Compared to studies focusing on metabolic disorders in relation to pollutants exposure, the impact of individual factors such as fatty liver on the in vivo metabolism of pollutants is always overlooked. Therefore, this study measured concentrations and composition of phthalate monoesters (mPAEs) in human urine samples, particularly those from fatty liver patients. Furthermore, we induced fatty liver in male Wistar rats by formulating a high-fat diet for twelve weeks. After administering a single dose of DEHP at 500 mg/kg bw through gavage, we compared the levels of di-2-ethylhexyl phthalate (DEHP), its metabolites (mDEHPs) and three hepatic metabolic enzymes, namely cytochrome P450 enzymes (CYP450), UDP glucuronosyltransferase 1 (UGT1), and carboxylesterase 1 (CarE1), between the normal and fatty liver rat groups. Compared to healthy individuals (n = 75), fatty liver patients (n = 104) exhibited significantly lower urinary concentrations of ∑mPAEs (median: 106 vs. 166 ng/mL), but with a higher proportion of mono-2-ethylhexyl phthalate in ∑mDEHPs (25.7 % vs. 9.9 %) (p < 0.05). In the animal experiment, we found that fatty liver in rats prolonged the elimination half-life of DEHP (24.61 h vs. 18.89 h) and increased the contents of CYP450, CarE1, and UGT1, implying the common but differentiated metabolism of DEHP as excess lipid accumulation in liver cells. This study provides valuable information on how to distinguish populations in biomonitoring studies across a diverse population and in assigning exposure classifications of phthalates or similar chemicals in epidemiologic studies.
Assuntos
Dietilexilftalato , Poluentes Ambientais , Hepatopatia Gordurosa não Alcoólica , Ácidos Ftálicos , Humanos , Masculino , Ratos , Animais , Dietilexilftalato/metabolismo , Exposição Ambiental , Ratos Wistar , Ácidos Ftálicos/urina , Poluentes Ambientais/metabolismo , BiomarcadoresRESUMO
The ecotoxic endocrine-disrupting chemical di-(2-ethylhexyl) phthalate (DEHP) is ubiquitous in agricultural soil, posing a serious threat to human health. Here, we report efficient soil-borne DEHP degradation and plant growth promotion by a microbial organic fertilizer GK-PPB prepared by combining a recycled garden waste-kitchen waste compost product with ternary compound microbial agent PPB-MA, composed of Penicillium oxalic MB08F, Pseudomonas simiae MB751, and Bacillus tequilensis MB05B. The combination of MB08F and MB751 provided synergistic phosphorus solubilization, and MB05B enhanced the DEHP degradation capacity of MB08F via bioemulsification. Under optimal conditions (25.70 °C and pH 7.62), PPB-MA achieved a 96.81 % degradation percentage for 1000 mg L-1 DEHP within 5 days. The degradation curve followed first-order kinetics with a half-life of 18.24 to 24.76 h. A complete mineralization pathway was constructed after identifying the degradation intermediates of 2H-labeled DEHP. Evaluation in Caenorhabditis elegans N2 showed that PPB-MA eliminated the ecological toxicity of DEHP. A pakchoi (Brassica chinensis L.) pot experiment demonstrated that GK-PPB promoted phosphorus solubilization and plant growth, reduced soil DEHP residue, and decreased DEHP accumulation in pakchoi, suggesting its potential practical utility in environmentally responsible and safe cultivation of vegetables.
Assuntos
Dietilexilftalato , Ácidos Ftálicos , Poluentes do Solo , Humanos , Dietilexilftalato/metabolismo , Fosfatos , Solo , Fósforo , Poluentes do Solo/análiseRESUMO
Plastic additives, represented by plasticizers, are important components of plastic pollution. Biofilms inevitably form on plastic surfaces when plastic enters the aqueous environment. However, little is known about the effect of biofilms on plastic surfaces on the release of additives therein. In this study, PVC plastics with different levels of di(2-ethylhexyl)phthalate (DEHP) content were investigated to study the effect of biofilm growth on DEHP release. The presence of biofilms promoted the migration of DEHP from PVC plastics to the external environment. Relative to biofilm-free controls, although the presence of surface biofilm resulted in 0.8 to 11.6 times lower DEHP concentrations in water, the concentrations of the degradation product, monoethylhexyl phthalate (MEHP) in water, were 2.3 to 57.3 times higher. When the total release amounts of DEHP in the biofilm and in the water were combined, they were increased by 0.6-73 times after biofilm growth. However, most of the released DEHP was adsorbed in the biofilms and was subsequently degraded. The results of this study suggest that the biofilm as a new interface between plastics and the surrounding environment can affect the transport and transformation of plastic additives in the environment through barrier, adsorption, and degradation. Future research endeavors should aim to explore the transport dynamics and fate of plastic additives under various biofilm compositions as well as evaluate the ecological risks associated with their enrichment by biofilms.
Assuntos
Dietilexilftalato , Dietilexilftalato/metabolismo , Plastificantes , Biofilmes , Poluição Ambiental , Água , PlásticosRESUMO
Di (2-ethylhexyl) phthalate (DEHP), identified as an endocrine-disrupting chemical, is associated with reproductive toxicity. This association is particularly noteworthy in newborns with incompletely developed metabolic functions, as exposure to DEHP can induce enduring damage to the reproductive system, potentially influencing adult reproductive health. In this study, we continuously administered 40 µg/kg and 80 µg/kg DEHP to postnatal day 5 (PD5) mice for ten days to simulate low and high doses of DEHP exposure during infancy. Utilizing single-cell RNA sequencing (scRNA-seq), our analysis revealed that varying concentrations of DEHP exposure during infancy induced distinct DNA damage response characteristics in testicular Undifferentiated spermatogonia (Undiff SPG). Specifically, DNA damage triggered mitochondrial dysfunction, leading to acetyl-CoA content alterations. Subsequently, this disruption caused aberrations in histone acetylation patterns, ultimately resulting in apoptosis of Undiff SPG in the 40 µg/kg DEHP group and autophagy in the 80 µg/kg DEHP group. Furthermore, we found that DEHP exposure impacts the development and functionality of Sertoli and Leydig cells through the focal adhesion and PPAR signaling pathways, respectively. We also revealed that Leydig cells regulate the metabolic environment of Undiff SPG via Ptn-Sdc4 and Mdk-Sdc4 after DEHP exposure. Finally, our study provided pioneering evidence that disruptions in testicular homeostasis induced by DEHP exposure during infancy endure into adulthood. In summary, this study elucidates the molecular mechanisms through which DEHP exposure during infancy influences the development of testicular cell populations.
Assuntos
Dietilexilftalato , Ácidos Ftálicos , Espermatogônias , Masculino , Camundongos , Animais , Dietilexilftalato/metabolismo , Histonas/metabolismo , Acetilação , Testículo/metabolismo , HomeostaseRESUMO
Di-n-butyl phthalate (DBP) is one of the most extensively used phthalic acid esters (PAEs) and is considered to be an emerging, globally concerning pollutant. The genus Streptomyces holds promise as a degrader of various organic pollutants, but PAE biodegradation mechanisms by Streptomyces species remain unsolved. In this study, a novel PAE-degrading Streptomyces sp. FZ201 isolated from natural habitats efficiently degraded various PAEs. FZ201 had strong resilience against DBP and exhibited immediate degradation, with kinetics adhering to a first-order model. The comprehensive biodegradation of DBP involves de-esterification, ß-oxidation, trans-esterification, and aromatic ring cleavage. FZ201 contains numerous catabolic genes that potentially facilitate PAE biodegradation. The DBP metabolic pathway was reconstructed by genome annotation and intermediate identification. Streptomyces species have an open pangenome with substantial genome expansion events during the evolutionary process, enabling extensive genetic diversity and highly plastic genomes within the Streptomyces genus. FZ201 had a diverse array of highly expressed genes associated with the degradation of PAEs, potentially contributing significantly to its adaptive advantage and efficiency of PAE degradation. Thus, FZ201 is a promising candidate for remediating highly PAE-contaminated environments. These findings enhance our preliminary understanding of the molecular mechanisms employed by Streptomyces for the removal of PAEs.
Assuntos
Dietilexilftalato , Poluentes Ambientais , Ácidos Ftálicos , Ésteres/metabolismo , Ácidos Ftálicos/metabolismo , Dibutilftalato/metabolismo , Biodegradação Ambiental , Ecossistema , Dietilexilftalato/metabolismoRESUMO
Di-(2-ethylhexyl) phthalate (DEHP) is an extensively used phthalate esters (PAEs) that raise growing ecotoxicological concerns due to detrimental effects on living organisms and ecosystems. This study performed hepatotoxic investigations on crucian carp under chronic low-dosage (CLD) exposure to DEHP at environmentally relevant concentrations (20-500 µg/L). The results demonstrated that the CLD exposure induced irreversible damage to the liver tissue. Multi-omics (transcriptomics and metabolomics) analyses revealed the predominant toxicological mechanisms underlying DEHP-induced hepatotoxicity by inhibiting energy production pathways and the up-regulation of the purine metabolism. Disruption of metabolic pathways led to excessive reactive oxygen species (ROS) production and subsequent oxidative stress. The adverse metabolic effects were exacerbated by an interplay between oxidative stress and endoplasmic reticulum stress. This study not only provides new mechanistic insights into the ecotoxicological effects of DEHP under chronic low-dosage exposure, but also suggests a potential strategy for further ecological risk assessment of PAEs.
Assuntos
Carpas , Dietilexilftalato , Ácidos Ftálicos , Animais , Dietilexilftalato/metabolismo , Ecossistema , Carpas/metabolismo , Multiômica , Ácidos Ftálicos/toxicidade , Ácidos Ftálicos/análiseRESUMO
Phthalic acid esters (PAEs) are widely used as plasticizers and have been suggested to engender adverse effects on glucose metabolism. However, epidemiological data regarding the PAE mixture on type 2 diabetes (T2DM), as well as the mediating role of oxidative stress are scarce. This case-control study enrolled 206 T2DM cases and 206 matched controls in Guangdong Province, southern China. The concentrations of eleven phthalate metabolites (mPAEs) and the oxidative stress biomarker 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine were determined. Additionally, biomarkers of T2DM in paired serum were measured to assess glycemic status and levels of insulin resistance. Significantly positive associations were observed for mono-(2-ethylhexyl) phthalate (MEHP) and Mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) with T2DM (P < 0.001). Restricted cubic spline modeling revealed a non-linear dose-response relationship between MEHHP and T2DM (Pnon-linear = 0.001). The Bayesian kernel machine regression and quantile g-computation analyses demonstrated a significant positive joint effect of PAE exposure on T2DM risk, with MEHHP being the most significant contributor. The mediation analysis revealed marginal evidence that oxidative stress mediated the association between the mPAEs mixture and T2DM, while 8-OHdG respectively mediated 26.88 % and 12.24 % of MEHP and MEHHP on T2DM risk individually (Pmediation < 0.05). Di(2-ethylhexyl) phthalate (DEHP, the parent compound for MEHP and MEHHP) was used to further examine the potential molecular mechanisms by in silico analysis. Oxidative stress may be crucial in the link between DEHP and T2DM, particularly in the reactive oxygen species metabolic process and glucose import/metabolism. Molecular simulation docking experiments further demonstrated the core role of Peroxisome Proliferator Activated Receptor alpha (PPARα) among the DEHP-induced T2DM. These findings suggest that PAE exposure can alter oxidative stress via PPARα, thereby increasing T2DM risk.
Assuntos
Diabetes Mellitus Tipo 2 , Dietilexilftalato , Dietilexilftalato/análogos & derivados , Ácidos Ftálicos , Humanos , Dietilexilftalato/toxicidade , Dietilexilftalato/metabolismo , Diabetes Mellitus Tipo 2/epidemiologia , Estudos de Casos e Controles , Teorema de Bayes , PPAR alfa/metabolismo , Ácidos Ftálicos/urina , 8-Hidroxi-2'-Desoxiguanosina/metabolismo , Estresse Oxidativo , Biomarcadores/metabolismo , Exposição Ambiental/efeitos adversosRESUMO
Polystyrene microplastic (PS-MPs) contamination has become a worldwide hotspot of concern, and its entry into organisms can cause oxidative stress resulting in multi-organ damage. The plasticizer di (2-ethylhexyl) phthalate (DEHP) is a common endocrine disruptor, these two environmental toxins often occur together, but their combined toxicity to the kidney and its mechanism of toxicity are unknown. Therefore, in this study, we established PS-MPS and/or DEHP-exposed mouse models. The results showed that alone exposure to both PS-MPs and DEHP caused inflammatory cell infiltration, cell membrane rupture, and content spillage in kidney tissues. There were also down-regulation of antioxidant enzyme levels, increased ROS content, activated of the NF-κB pathway, stimulated the levels of heat shock proteins (HSPs), pyroptosis, and inflammatory associated factors. Notably, the co-exposure group showed greater toxicity to kidney tissues, the cellular assay further validated these results. The introduction of the antioxidant n-acetylcysteine (NAC) and the NLRP3 inhibitor (MCC950) could mitigate the changes in the above measures. In summary, co-exposure of PS-MPs and DEHP induced oxidative stress that activated the NF-κB/NLRP3 pathway and aggravated kidney pyroptosis and inflammation, as well as that HSPs are also involved in this pathologic injury process. This study not only enriched the nephrotoxicity of plasticizers and microplastics, but also provided new insights into the toxicity mechanisms of multicomponent co-pollution in environmental.
Assuntos
Dietilexilftalato , Microplásticos , Estresse Oxidativo , Ácidos Ftálicos , Piroptose , Animais , Camundongos , Antioxidantes/metabolismo , Dietilexilftalato/toxicidade , Dietilexilftalato/metabolismo , Inflamação/induzido quimicamente , Rim/metabolismo , Microplásticos/metabolismo , Microplásticos/toxicidade , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Plastificantes/toxicidade , Plastificantes/metabolismo , Plásticos/metabolismo , Plásticos/toxicidade , Poliestirenos/toxicidade , Poliestirenos/metabolismoRESUMO
This study investigates the mechanism behind the oxidation di-(2-ethylhexyl) phthalate (DEHP) in marine sediment by coupling sulfite using biochar prepared from sorghum distillery residue (SDRBC). The rationale for this investigation stems from the need to seek effective methods for DEHP-laden marine sediment remediation. The aim is to assess the feasibility of sulfite-based advanced oxidation processes for treating hazardous materials such as DEHP containing sediment. To this end, the sediment in question was treated with 2.5 × 10-5 M of sulfite and 1.7 g L-1 of SDRBC700 at acidic pH. Additionally, the study demonstrated that the combination of SDRBC/sulfite with a bacterial system enhances DEHP removal. Thermostilla bacteria were enriched, highlighting their role in sediment treatment. This study concludes that sulfite-associated sulfate radicals-driven carbon advanced oxidation process (SR-CAOP) offers sustainable sediment pretreatment through the SDRBC/sulfite-mediated microbial consortium, in which the SO3â¢- and 1O2 were responsible for DEHP degradation. SDRBC/sulfite offers an effective and environmentally friendly method for removing DEHP. Further, these results can be targeted at addressing industry problems related to sediment treatment.
Assuntos
Carvão Vegetal , Dietilexilftalato , Microbiota , Ácidos Ftálicos , Sorghum , Dietilexilftalato/metabolismo , Sorghum/metabolismo , Ácidos Ftálicos/química , Sedimentos GeológicosRESUMO
Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer known to pose health risks to humans upon exposure. Recognizing the toxic nature of DEHP, our study aimed to elucidate the response mechanisms in Brassica chinensis L. (Shanghai Qing) when subjected to varying concentrations of DEHP (2 mg kg-1, 20 mg kg-1, and 50 mg kg-1), particularly under tissue stress. The findings underscored the substantial impact of DEHP treatment on the growth of Brassica chinensis L., with increased DEHP concentration leading to a notable decrease in chlorophyll levels and alterations in the content of antioxidant enzyme activities, particularly superoxide dismutase (SOD) and peroxidase (POD). Moreover, elevated DEHP concentrations correlated with increased malondialdehyde (MDA) levels. Our analysis detected a total of 507 metabolites in Brassica chinensis L., with 331 in shoots and 176 in roots, following DEHP exposure. There was a significant difference in the number of metabolites in shoots and roots, with 79 and 64 identified, respectively (VIP > 1, p < 0.05). Metabolic pathway enrichment in Brassica chinensis L. shoots revealed significant perturbations in valine, leucine, and isoleucine biosynthesis and degradation, aminoacyl-tRNA, and glucosinolate biosynthesis. In the roots of Brassica chinensis L., varying DEHP levels exerted a substantial impact on the biosynthesis of zeatin, ubiquinone terpenoids, propane, piperidine, and pyridine alkaloids, as well as glutathione metabolic pathways. Notably, DEHP's influence was more pronounced in the roots than in the shoots, with higher DEHP concentrations affecting a greater number of metabolic pathways. This experimental study provides valuable insights into the molecular mechanisms underlying DEHP-induced stress in Brassica chinensis L., with potential implications for human health and food safety.
Assuntos
Brassica , Dietilexilftalato , Ácidos Ftálicos , Humanos , Dietilexilftalato/metabolismo , China , Ácidos Ftálicos/metabolismo , Antioxidantes/metabolismo , Brassica/metabolismoRESUMO
Di-(2-ethylhexyl) phthalate (DEHP), as the most common phthalate, has been extensively used as a plasticizer to improve the plasticity of agricultural products, which pose severe harm to human health. Mitochondrial dynamics and endoplasmic reticulum (ER) homeostasis are indispensable for maintaining mitochondria-associated ER membrane (MAM) integrity. In this study, we aimed to explore the effect of DEHP on the nervous system and its association with the ER-mitochondria interaction. Here, we showed that DEHP caused morphological changes, motor deficits, cognitive impairments, and blood-brain barrier disruption in the brain. DEHP triggered ER stress, which is mainly mediated by protein kinase R-like endoplasmic reticulum kinase (PERK) signaling. Moreover, DEHP-induced mitofusin-2 (Mfn2) downregulation results in imbalance of the mitochondrial dynamics. Interestingly, DEHP exposure impaired MAMs by inhibiting the Mfn2-PERK interaction. Above all, this study elucidates the disruption of the Mfn2-PERK axis-mediated ER-mitochondria interaction as a phthalate-induced neurotoxicity that could be potentially developed as a novel therapy for neurological diseases.
Assuntos
Dietilexilftalato , Ácidos Ftálicos , Humanos , Dietilexilftalato/toxicidade , Dietilexilftalato/metabolismo , Mitocôndrias/metabolismo , Ácidos Ftálicos/toxicidade , Ácidos Ftálicos/metabolismo , Estresse do Retículo Endoplasmático , Retículo Endoplasmático/metabolismo , Hidrolases/metabolismoRESUMO
The intensive accumulation of di-2-ethylhexyl phthalate (DEHP) in agricultural soils has resulted in severe environmental pollution that endangers ecosystem and human health. Biochar is an eco-friendly material that can help in accelerating organic pollutant degradation; nevertheless, its roles in enhancing DEHP removal in rhizosphere remain unclear. This work investigated the impacts of biochar dosage (0%-2.0%) on DEHP degradation performance in tomato rhizosphere by comprehensively exploring the change in DEHP metabolites, bacterial communities and DEHP-degrading genes. Our results showed a significant increase of rhizosphere pH, organic matter and humus by biochar amendment, which achieved a satisfactorily higher DEHP removal efficiency, maximally 77.53% in treatments with 1.0% of biochar. Biochar addition also remarkably changed rhizosphere bacterial communities by enriching some potential DEHP degraders of Nocardioides, Sphingomonas, Bradyrhizobium and Rhodanobacter. The abundance of genes encoding key enzymes (hydrolase, esterase and cytochrome P450) and DEHP-degrading genes (pht3, pht4, pht5, benC-xylZ and benD-xylL) were increased after biochar amendment, leading to the change in DEHP degradation metabolism, primarily from benzoic acid pathway to protocatechuic acid pathway. Our findings evidenced that biochar amendment could accelerate DEHP degradation by altering rhizosphere soil physicochemical variables, bacterial community composition and metabolic genes, providing clues for the mechanisms of biochar-assisted DEHP degradation in organic contaminated farmland soils.