RESUMO
Field research on phthalate monoesters (MPEs) and their relationships with phthalate esters (PAEs) is limited, especially in wild fishes. Here, PAEs and MPEs were measured in surface water, sediment, and wild fish collected from a representative river basin with high economic development. Several metabolites of emerging plasticizers, such as mono(3,5,5-trimethyl-1-hexyl) phthalate and mono(6-oxo-2-propylheptyl) phthalate, have already existed in fish with high detection frequencies (95 % and 100 %). Monobutyl phthalate and mono(2-ethylhexyl) phthalate were the predominant MPEs in fish and natural environment (surface water and sediment), while bis(2-ethylhexyl) phthalate was the most abundant PAEs in all matrices. The total concentrations (median) of 9 PAEs and 16 MPEs were 5980 and 266 ng/L in water, 231 and 10.6 ng/g (dw) in sediment, and 209 and 32.5 ng/g (ww) in fish, respectively. The occurrence of MPEs was highly related to their parent PAEs, with similar spatial distribution characteristics in the aquatic environments. Moreover, municipal wastewater discharge was recognized as the main source of MPEs in the research area. Fish species can accumulate targeted chemicals, and it seems more MPEs were from the PAE degradation in fish other than the direct uptake of MPEs in water. Parent PAEs showed higher ecological risk than their corresponding metabolites.
Assuntos
Monitoramento Ambiental , Ésteres , Peixes , Sedimentos Geológicos , Ácidos Ftálicos , Poluentes Químicos da Água , Ácidos Ftálicos/análise , Ácidos Ftálicos/metabolismo , Poluentes Químicos da Água/análise , Animais , Peixes/metabolismo , Sedimentos Geológicos/química , Sedimentos Geológicos/análise , Ésteres/análise , Rios/química , Plastificantes/análise , Plastificantes/metabolismo , Medição de RiscoRESUMO
Phthalate esters (PAEs) are widely used as plasticizers and cause serious complex pollution problem in environment. Thus, strains with efficient ability to simultaneously degrade various PAEs are required. In this study, a newly isolated strain Rhodococcus sp. AH-ZY2 can degrade 500 mg/L Di-n-octyl phthalate completely within 16 h and other 500 mg/L PAEs almost completely within 48 h at 37 °C, 180 rpm, and 2 % (v/v) inoculum size of cultures with a OD600 of 0.8. OD600 = 0.8, 2 % (v/v). Twenty genes in its genome were annotated as potential esterase and four of them (3963, 4547, 5294 and 5359) were heterogeneously expressed and characterized. Esterase 3963 and 4547 is a type I PAEs esterase that hydrolyzes PAEs to phthalate monoesters. Esterase 5294 is a type II PAEs esterase that hydrolyzes phthalate monoesters to phthalate acid (PA). Esterase 5359 is a type III PAEs esterase that simultaneously degrades various PAEs to PA. Molecular docking results of 5359 suggested that the size and indiscriminate binding feature of spacious substrate binding pocket may contribute to its substrate versatility. AH-ZY2 is a potential strain for efficient remediation of PAEs complex pollution in environment. It is first to report an esterase that can efficiently degrade mixed various PAEs.
Assuntos
Biodegradação Ambiental , Esterases , Ésteres , Simulação de Acoplamento Molecular , Ácidos Ftálicos , Rhodococcus , Rhodococcus/metabolismo , Rhodococcus/genética , Rhodococcus/enzimologia , Ácidos Ftálicos/metabolismo , Ácidos Ftálicos/química , Esterases/metabolismo , Esterases/genética , Ésteres/metabolismo , Ésteres/química , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Plastificantes/metabolismoRESUMO
Phthalate isomers are key intermediates in the biodegradation of pollutants including waste polyethylene terephthalate (PET) plastics and plasticizers. So far, an increasing number of phthalate isomer-degrading strains have been isolated, and their degradation pathways show significant diversity. In this paper, we comprehensively review the current status of research on the degrading bacteria, degradation characteristics, aerobic and anaerobic degradation pathways, and degradation genes (clusters) of phthalate isomers, and discuss the current shortcomings and challenges. Moreover, the degradation process of phthalate isomers produces many important aromatic precursor molecules, which can be used to produce higher-value derivative chemicals, and the modification of their degradation pathways holds good prospects. Therefore, this review also highlights the current progress made in modifying the phthalate isomer degradation pathway and explores its potential for high-value applications.
Assuntos
Bactérias , Biodegradação Ambiental , Ácidos Ftálicos , Ácidos Ftálicos/metabolismo , Bactérias/metabolismo , Bactérias/genética , Bactérias/classificação , Isomerismo , Plastificantes/metabolismo , Poluentes Ambientais/metabolismo , Redes e Vias Metabólicas , Polietilenotereftalatos/metabolismo , Polietilenotereftalatos/químicaRESUMO
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
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
Due to the lack of research on the co-effects of microplastics and trace metals in the environment on nitrogen cycling-related functional microorganisms, the occurrence of microplastics and one of their plasticisers, phthalate esters, as well as trace metals, were determined in soils and river sediments in the Qinghai-Tibet Plateau. Relationship between microplastics and phthalate esters in the area was determined; the co-effects of these potentially toxic materials, and key factors and pathways affecting nitrogen functions were further explored. Significant correlations between fibre- and film-shaped microplastics and phthalate esters were detected in the soils from the plateau. Copper, lead, cadmium and di-n-octyl phthalate detected significantly affected nitrogen cycling-related functional microorganisms. The co-existence of di-n-octyl phthalate and copper in soils synergistically stimulated the expression of denitrification microorganisms nirS gene and "nitrate_reduction". Additionally, di-n-octyl phthalate and dimethyl phthalate more significantly affected the variation of nitrogen cycling-related functional genes than the number of microplastics. In a dimethyl phthalate- and cadmium-polluted area, nitrogen cycling-related functional genes, especially nirK gene, were more sensitive and stressed. Overall, phthalate esters originated from microplastics play a key role in nitrogen cycling-related functions than microplastics themselves, moreover, the synergy between di-n-octyl phthalate and copper strengthen the expression of denitrification functions.
Assuntos
Desnitrificação , Microplásticos , Microbiologia do Solo , Poluentes do Solo , Desnitrificação/efeitos dos fármacos , Poluentes do Solo/toxicidade , Poluentes do Solo/metabolismo , Tibet , Microplásticos/toxicidade , Plastificantes/toxicidade , Plastificantes/metabolismo , Microbiota/efeitos dos fármacos , Ácidos Ftálicos/toxicidade , Ácidos Ftálicos/metabolismo , Sedimentos Geológicos/microbiologia , Sedimentos Geológicos/química , Metais Pesados/toxicidadeRESUMO
Phthalic acid esters (PAEs) are human made chemicals widely used as plasticizers to enhance the flexibility of plastic products. Due to the lack of chemical bonding between phthalates and plastics, these materials can easily enter the environment. Deleterious effects caused by this chemo-pollutant have drawn the attention of the scientific community to remediate them from different ecosystem. In this context, many bacterial strains have been reported across different habitats and Sphingobium yanoikuyae strain P4 is among the few psychrotolerant bacterial species reported to biodegrade simple and complex phthalates. In the present study, biodegradation of three structurally different PAEs viz., diethyl phthalate (DEP), di-isobutyl phthalate (DIBP), and butyl benzyl phthalate (BBP) have been investigated by the strain P4. Quantitative analyses through High-performance liquid chromatography (HPLC) revealed that the bacterium completely degraded 1 g/L of DEP, DIBP, and BBP supplemented individually in minimal media pH 7.0 within 72, 54, and 120 h of incubation, respectively, at 28 °C and under shake culture condition (180 rpm). In addition, the strain could grow in minimal media supplemented individually with up to 3 g/L of DEP and 10.0 g/L of DIBP and BBP at 28 °C and pH 7.0. The strain also could grow in metabolites resulting from biodegradation of DEP, DIBP, and BBP, viz. n-butanol, isobutanol, butyric acid, ethanol, benzyl alcohol, benzoic acid, phthalic acid, and protocatechuic acid. Furthermore, phthalic acid and protocatechuic acid were also detected as degradation pathway metabolites of DEP and DIBP by HPLC, which gave an initial idea about the biodegradation pathway(s) of these phthalates.
Assuntos
Biodegradação Ambiental , Ácidos Ftálicos , Sphingomonadaceae , Ácidos Ftálicos/metabolismo , Sphingomonadaceae/metabolismo , Sphingomonadaceae/genética , Dibutilftalato/metabolismo , Plastificantes/metabolismo , Cromatografia Líquida de Alta Pressão , Hidroxibenzoatos/metabolismoRESUMO
The widely existed plastic additives plasticizers in organic wastes possibly pose negative influences on anaerobic digestion (AD) performance, the direct evidence about the effects of plasticizers on AD performance is still lacking. This study evaluated the influencing mechanism of two typical plasticizers bisphenol A (BPA) and dioctyl phthalate on the whole AD process. Results indicated that plasticizers addition inhibited methane production, and the inhibiting effects were reinforced with the increase of concentration. By contrast, 50 mg/L BPA exhibited the strongest inhibition on methane production. Physicochemical analysis showed plasticizers inhibited the metabolism efficiency of soluble polysaccharide and volatile fatty acids. Microbial communities analyses suggested that plasticizers inhibited the direct interspecies electron transfer participators of methanogenic archaea (especially Methanosarcina) and syntrophic bacteria. Furthermore, plasticizers inhibited the methane metabolisms, key coenzymes (CoB, CoM, CoF420 and methanofuran) biosynthesis and the metabolisms of major organic matters. This study shed light on the effects of plasticizers on AD performance and provided new insights for assessing the influences of plasticizers or plastic additives on the disposal of organic wastes.
Assuntos
Compostos Benzidrílicos , Metano , Fenóis , Plastificantes , Anaerobiose , Plastificantes/metabolismo , Metano/metabolismo , Compostos Benzidrílicos/metabolismo , Fenóis/metabolismo , Ácidos Graxos Voláteis/metabolismo , Bactérias/metabolismo , Bactérias/efeitos dos fármacos , Reatores Biológicos , Eliminação de Resíduos/métodos , Ácidos Ftálicos/metabolismo , Alimentos , Perda e Desperdício de AlimentosRESUMO
This study investigated the leaching of phthalate and non-phthalate plasticizers from polyvinyl chloride microplastics (MPs) into sediment and their degradation over a 30-d period via abiotic and biotic processes. The results showed that 3579% of plasticizers were released into the sediment from the MPs and > 99.9% degradation was achieved. Although a significantly higher degradation was found in plasticizer-added microcosms under biotic processes (overall, 94%), there was a noticeable abiotic loss (72%), suggesting that abiotic processes also play a role in plasticizer degradation. Interestingly, when compared with the initial sediment-water partitioning for plasticizers, the partition constants for low-molecular-weight compounds decreased in both microcosms, whereas those for high-molecular-weight compounds increased after abiotic degradation. Furthermore, changes in the bacterial community, abundance of plasticizer-degrading bacterial populations, and functional gene profiles were assessed. In all the microcosms, a decrease in bacterial community diversity and a notable shift in bacterial composition were observed. The enriched potential plasticizer-degrading bacteria were Arthrobacter, Bacillus, Desulfovibrio, Desulfuromonas, Devosia, Gordonia, Mycobacterium, and Sphingomonas, among which Bacillus was recognized as the key plasticizer degrader. Overall, these findings shed light on the factors affecting plasticizer degradation, the microbial communities potentially involved in biodegradation, and the fate of plasticizers in the environment.
Assuntos
Bactérias , Sedimentos Geológicos , Microplásticos , Ácidos Ftálicos , Plastificantes , Cloreto de Polivinila , Poluentes Químicos da Água , Cloreto de Polivinila/química , Plastificantes/metabolismo , Sedimentos Geológicos/microbiologia , Sedimentos Geológicos/química , Ácidos Ftálicos/metabolismo , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/metabolismo , Bactérias/metabolismo , Bactérias/classificação , Biodegradação AmbientalRESUMO
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
Widespread application of the typical phthalate plasticizers, di (2-ethylhexyl) phthalate (DEHP), poses a serious potential threat to the health of animals and even humans. Previous studies have confirmed the mechanism of DEHP-induced cardiac developmental defects in zebrafish larvae. However, the mechanism of cardiac dysfunction is still unclear. Thus, this work aimed to comprehensively investigate the mechanisms involved in DEHP-induced cardiac dysfunction through computational simulations, in vivo assays in zebrafish, and in vitro assays in cardiomyocytes. Firstly, molecular docking and western blot initially investigated the activating effect of DEHP on Pparg in zebrafish. Although GW9662 (PPARG antagonist) effectively alleviated DEHP-induced cardiac dysfunction and lipid metabolism disorders, it did not restore significant decreases in mitochondrial membrane potential and ATP levels. In vitro assays in cardiomyocytes, DEHP caused overexpression of PPARG and proteins involved in the regulation of Ca2+ homeostasis, and the above abnormalities were effectively alleviated by GW9662, suggesting that the Ca2+ homeostatic imbalance caused by activation of PPARG by DEHP seems to be the main cause of DEHP-induced cardiac dysfunction. To sum up, this work not only refines the mechanism of toxic effects of cardiotoxicity induced by DEHP, but provides an important theoretical basis for enriching the toxicological effects of DEHP.
Assuntos
Anilidas , Dietilexilftalato , Cardiopatias , Ácidos Ftálicos , Humanos , Animais , Dietilexilftalato/toxicidade , Dietilexilftalato/metabolismo , Peixe-Zebra/metabolismo , PPAR gama/metabolismo , Simulação de Acoplamento Molecular , Plastificantes/toxicidade , Plastificantes/metabolismoRESUMO
The incidence of metabolic diseases is increasing alarmingly in recent times. Parallel to nutritional excess and sedentary lifestyle, the random usage of several endocrine disrupting chemicals including plasticizers is reported to be closely associated with metabolic diseases. Diethyl phthalate (DEP) is a widely used plasticizer in a host of consumer and daily care products. Adipose tissue plays a central role in energy storage and whole-body metabolism. The impairment of adipose function is critically implicated in the pathogenesis of insulin resistance, diabetes, and related metabolic diseases. Recently, exposure to certain phthalate esters has been linked to the development of obesity and diabetes, although there are contradictions and the mechanisms are not clearly understood. In an effort to ascertain the metabolic consequences of chronic phthalate exposure and the underlying mechanism, the present study was designed to examine the effects of long-term dietary consumption of DEP in adipocytes. DEP-treated mice were hyperglycemic but nonobese; their body weight initially increased which subsequently was reduced compared to control. DEP exposure at lower levels impaired adipogenesis by downregulating the key transcription factor, peroxisome proliferator-activated receptor γ and its downstream insulin-sensitizing adipokine, adiponectin, thereby severely compromising adipocyte function. The activation of master regulator nuclear factor κB led to rise in proinflammatory cytokines. We found that DEP triggered intrinsic apoptotic pathways through activated cytochrome c-Apaf1-caspase 9-caspase 3 axis in adipocytes. Taken together, our data revealed that chronic administration of dietary DEP could unleash adverse metabolic outcomes by initiating oxidative stress, inflammation, and apoptosis in the adipocytes, thus leading to adipose tissue dysfunction.
Assuntos
Diabetes Mellitus , Resistência à Insulina , Ácidos Ftálicos , Camundongos , Animais , Plastificantes/toxicidade , Plastificantes/metabolismo , Adipócitos , Obesidade/induzido quimicamente , Obesidade/metabolismo , Diabetes Mellitus/metabolismo , Apoptose , Inflamação/induzido quimicamente , Inflamação/metabolismoRESUMO
In response to the restriction of phthalate plasticizers, acetyl tributyl citrate (ATBC) and acetyl triethyl citrate (ATEC) have been used in medical devices and food packaging. In the present study, the effects of ATBC and ATEC on the development, behavior, growth hormone (GH)-related endocrine system, neurotransmitters, and oxidative stress of zebrafish embryo or larvae were investigated. After exposure of zebrafish to ATBC and ATEC (0, 0.03, 0.3, 3, 30, and 300 µg/L) for 96 h, developmental toxicity, behavioral changes under light/dark condition, changes in hormones and genes involved in GH/insulin-like growth factors (IGFs) axis, changes in hormone, enzyme, and genes related to neurodevelopment, antioxidant enzymes activities were determined. Larvae exposed to 30 or 300 µg/L ATBC showed significant reductions in body length and moving distance and speed, whereas no significant effects on development and locomotor behavior were observed in larvae exposed to ATEC. The contents of GH and IGF-I were significantly reduced in larvae exposed to 3, 30, and 300 µg/L ATBC. Hormonal changes in fish exposed to ATBC are well supported by regulation of genes related to GH (gh1) and the activity of IGF-I (igf1). In fish exposed to ATBC, reduced acetylcholinesterase activity and down-regulation of genes related to the central nervous system development (ache, gap43, mbpa, and syn21) were observed. ATBC increased the production of reactive oxygen species and the levels of superoxide dismutase, catalase, and glutathione peroxidase. Notably, pre-treatment with the classic antioxidant N-acetylcysteine alleviated ATBC-induced GH-related endocrine disruption and neurotoxicity. Our observations showed that exposure to low levels of ATBC could disturb the regulatory systems of GH/IGFs axis and neurobehavior, ultimately leading to developmental inhibition and hypoactivity, and that increased oxidative stress plays a major role in these toxicities.
Assuntos
Plastificantes , Poluentes Químicos da Água , Animais , Plastificantes/metabolismo , Hormônio do Crescimento/genética , Hormônio do Crescimento/metabolismo , Hormônio do Crescimento/farmacologia , Peixe-Zebra/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Larva/metabolismo , Antioxidantes/metabolismo , Acetilcolinesterase/metabolismo , Sistema Endócrino , Estresse Oxidativo , Poluentes Químicos da Água/toxicidade , Embrião não MamíferoRESUMO
As one of the common plasticizers, di-n-butyl phthalate (DBP) has been using in various daily consumer products worldwide. Since it is easily released from products and exists in the environment for a long time, it has a lasting impact on human health, especially male reproductive health. However, the detailed mechanism of testicular damage from DBP and the protection strategy are still not clear enough. In this study, we found that DBP could induce dose-dependent ferroptosis in testicular tissue. Mechanism dissection indicates that DBP can upregulate SP1 expression, which could directly transcriptionally upregulate PRDX6, a negative regulator of ferroptosis. Overexpression of PRDX6 or adding SP1 agonist curcumin could suppress the DBP-induced ferroptosis on testicular cells. In vivo, rats were given 500 mg/kg/day DBP orally for 3 weeks; elevated levels of ferroptosis were detected in testicular tissue. When the above-mentioned doses of DBP and curcumin at a dose of 300 mg/kg/day were administered intragastrically simultaneously, the testicular ferroptosis induced by DBP was alleviated. Immunohistochemistry and quantitative real-time PCR of testis tissue showed that the expression of PRDX6 was upregulated under the action of DBP and curcumin. These findings suggest a spontaneous self-protection mechanism of testicular tissue from DBP damage by upregulating SP1 and PRDX6. However, it is not strong enough to resist the DBP-induced ferroptosis. Curcumin can strengthen this self-protection mechanism and weaken the level of ferroptosis induced by DBP. This study may help us to develop a novel therapeutic option with curcumin to protect the testicular tissue from ferroptosis and function impairment by DBP.
Assuntos
Curcumina , Ferroptose , Ratos , Masculino , Humanos , Animais , Testículo , Dibutilftalato/toxicidade , Dibutilftalato/metabolismo , Curcumina/farmacologia , Curcumina/metabolismo , Plastificantes/toxicidade , Plastificantes/metabolismo , Peroxirredoxina VI/genética , Peroxirredoxina VI/metabolismoRESUMO
The aim of this study was to explore the adverse effects of a microplastic (MP) mixture obtained from litter accumulated in the Seine River (France) compared to those of their major co-plasticizer, dibutylphthalate (DBP), on the sentinel species Hediste diversicolor. A suite of biomarkers has been investigated to study the impacts of MPs (100 mg kg-1 sediment), DBP (38 µg kg-1 sediment) on worms compared to non-exposed individuals after 4 and 21 days. The antioxidant response, immunity, neurotoxicity and energy and respiratory metabolism were investigated using biomarkers. After 21 days, worms exposed to MPs showed an increasing aerobic metabolism, an enhancement of both antioxidant and neuroimmune responses. Energy-related biomarkers demonstrated that the energy reallocated to the defence system may come from proteins. A similar impact was depicted after DBP exposure, except for neurotoxicity. Our results provide a better understanding of the ecotoxicological effects of environmental MPs and their associated-contaminants on H. diversicolor.
Assuntos
Poliquetos , Poluentes Químicos da Água , Humanos , Animais , Microplásticos , Espécies Sentinelas/metabolismo , Antioxidantes , Plastificantes/toxicidade , Plastificantes/metabolismo , Plásticos/toxicidade , Rios , Dibutilftalato/toxicidade , Dibutilftalato/metabolismo , Biomarcadores/metabolismo , Poliquetos/fisiologia , Poluentes Químicos da Água/metabolismoRESUMO
OBJECTIVES: To explore the effect of exposure to di (2-ethyl) hexyl phthalate (DEHP) in early pregnancy on endometrial decidualization in mice and its relation with lncRNA RP24-315D19.10. METHODS: Early pregnancy mice were exposed to DEHP (1000 mg·kgï¼1·dï¼1) to construct the model. The uterus was collected on day 6 of pregnancy to detect its effect on decidualization by HE staining and immunofluorescence. A decidualization induction model of mouse endometrial stromal cells exposed to DEHP (0.1, 0.5, 2.5, 12.5, 62.5 µmol/L) was constructed. The changes of cell morphology were observed by light microscopy and phalloidin staining, and the expression of decidual reaction related molecular markers were detected by immunofluorescence, realtime RT-PCR and Western blotting. The expression of RP24-315D19.10 in decidua tissue and cells was detected by realtime RT-PCR. Cellular localization of RP24-315D19.10 was determined by lncLocator database and RNA FISH. AnnoLnc2 database was used to predict miRNAs bound to RP24-315D19.10. RESULTS: The number of embryo implantation sites, uterine weight and uterine area were significantly lower in the DEHP exposed group than those in the control group, and the expression of the decidual reaction related molecular markers matrix metalloprotein 9 and homeobox A10 in the DEHP exposure group were also significantly lower than those in the control group (all P<0.05). With the increase of DEHP concentration, the expression of dtprp in decidua cells was gradually decreased. 2.5 µmol/L DEHP exposed stromal cells failed to be fully decidualized in vitro, andphalloidin staining showed abnormal cytoskeleton morphology. The expression levels of homeobox A10, bone morphogenetic protein 2 and proliferating cell nuclear antigen in the DEHP exposure group were significantly lower than those in the control group (all P<0.05). The expression of RP24-315D19.10 in DEHP exposed decidua tissue and cells was significantly reduced (both P<0.05). RP24-315D19.10 is mainly localized in the cytoplasm and RP24-315D19.10 might bind to 45 miRNAs, among them, miR-138-5p, miR-155-5p, miR-183-5p and miR-223-3p were associated with endometrial decidualization. CONCLUSIONS: DEHP exposure in early pregnancy may impair endometrial decidualization, and the damage may be associated with the down-regulation of RP24-315D19.10.
Assuntos
Dietilexilftalato , MicroRNAs , RNA Longo não Codificante , Gravidez , Feminino , Camundongos , Animais , Decídua/metabolismo , RNA Longo não Codificante/metabolismo , Dietilexilftalato/toxicidade , Dietilexilftalato/metabolismo , Plastificantes/toxicidade , Plastificantes/metabolismo , Proteínas Homeobox A10/metabolismo , Endométrio , MicroRNAs/metabolismo , Células Estromais/metabolismoRESUMO
Phthalate diesters are extensively used as plasticizers in manufacturing plastic materials; however, because of their estrogenic properties, these chemicals have emerged as a global threat to human health. The present study investigated the course of degradation of a widely used plasticizer, benzyl butyl phthalate (BBP), by the bacterium PAE-6, belonging to the genus Rhodococcus. The metabolism of BBP, possessing structurally dissimilar side chains, was evaluated biochemically using a combination of respirometric, chromatographic, enzymatic, and mass-spectrometric analyses, depicting pathways of degradation. Consequently, the biochemical observations were corroborated by identifying possible catabolic genes from whole-genome analysis, and the involvement of inducible specific esterases and other degradative enzymes was validated by transcriptomic, reverse transcription-quantitative PCR (RT-qPCR) and proteomic analyses. Nonetheless, phthalic acid (PA), an intermediate of BBP, could not be efficiently metabolized by strain PAE-6, although the genome contains a PA-degrading gene cluster. This deficiency of complete degradation of BBP by strain PAE-6 was effectively managed by using a coculture of strains PAE-6 and PAE-2. The latter was identified as a Paenarthrobacter strain which can efficiently utilize PA. Based on sequence analysis of the PA-degrading gene cluster in strain PAE-6, it appeared that the alpha subunit of the multicomponent phthalate 3,4-dioxygenase harbors a number of altered residues in the multiple sequence alignment of homologous subunits, which may play a role(s) in poor turnover of PA. IMPORTANCE Benzyl butyl phthalate (BBP), an estrogenic, high-molecular-weight phthalic acid diester, is an extensively used plasticizer throughout the world. Due to its structural rigidity and hydrophobic nature, BBP gets adsorbed on sediments and largely escapes the biotic and abiotic degradative processes of the ecosystem. In the present study, a potent BBP-degrading bacterial strain belonging to the genus Rhodococcus was isolated that can also assimilate a number of other phthalate diesters of environmental concern. Various biochemical and multi-omics analyses revealed that the strain harbors all the required catabolic machinery for the degradation of the plasticizer and elucidated the inducible regulation of the associated catabolic genes and gene clusters.
Assuntos
Plastificantes , Rhodococcus , Humanos , Plastificantes/química , Plastificantes/metabolismo , Rhodococcus/genética , Rhodococcus/metabolismo , Proteômica , Ecossistema , MultiômicaRESUMO
Female reproductive lifespan is largely determined by the size of the primordial follicle pool, which is established in early life. Dibutyl phthalate (DBP), a popular plasticiser, is a known environmental endocrine disruptor that poses a potential threat to reproductive health. However, DBP impact on early oogenesis has been rarely reported. In this study, maternal exposure to DBP in gestation disrupted germ-cell cyst breakdown and primordial follicle assembly in foetal ovary, impairing female fertility in adulthood. Subsequently, altered autophagic flux with autophagosome accumulation was observed in DBP-exposed ovaries carrying CAG-RFP-EGFP-LC3 reporter genes, whereas autophagy inhibition by 3-methyladenine attenuated the impact of DBP on primordial folliculogenesis. Moreover, DBP exposure reduced the expression of NOTCH2 intracellular domain (NICD2) and decreased interactions between NICD2 and Beclin-l. NICD2 was observed within the autophagosomes in DBP-exposed ovaries. Furthermore, NICD2 overexpression partially restored primordial folliculogenesis. Furthermore, melatonin significantly relieved oxidative stress, decreased autophagy, and restored NOTCH2 signalling, consequently reversing the effect on folliculogenesis. Therefore, this study demonstrated that gestational DBP exposure disrupts primordial folliculogenesis by inducing autophagy, which targets NOTCH2 signalling, and this impact has long-term consequences on fertility in adulthood, strengthening the potential contribution of environmental chemicals to the development of ovarian dysfunctional diseases.
Assuntos
Dibutilftalato , Folículo Ovariano , Animais , Feminino , Camundongos , Autofagia , Dibutilftalato/toxicidade , Dibutilftalato/metabolismo , Ovário , Plastificantes/metabolismo , Receptor Notch2/química , Receptor Notch2/metabolismoRESUMO
Plasticizers are broadly classified as phthalate or nonphthalate. Recently, acetyl tributyl citrate (ATBC), an environmentally friendly nonphthalate plasticizer, was revealed to have the ability to disrupt thyroid hormone activity in fish species. Therefore, we aimed to assess whether ATBC exhibits any sex hormone (i.e., androgenic or estrogenic) activities. First, we examined the effects of ATBC on gonadal sex differentiation. Subsequently, we analyzed the different expression of biomarker genes that respond to endocrine-disrupting chemicals (EDCs) with sexual hormone activity in the liver. We observed normal testes and ovaries after both XX and XY medakas were exposed to ATBC, indicating that ATBC is not an EDCs with strong sex hormone activity and that it does not induce intersex (testis-to-ova or ovo-to-testis) or sex changes in Japanese medaka. The vitellogenin 1 (vtg1) and vitellogenin 2 (vtg2) mRNA expression levels in the liver of XX medakas were significantly reduced compared with those in the control group, whereas the expression levels of these genes in the liver of XY medakas remained unchanged. Finally, we examined the changes in the expression of biomarker genes that respond to EDCs with sex hormone activity in the gonads. The expression levels of biomarker genes did not differ significantly from that of the control group, although the expression levels of gsdf mRNA tended to increase while that of aromatase mRNA tended to decrease in the ovary of XX medakas following ATBC exposure. Conversely, the expression levels of gsdf and aromatase mRNAs in the testis of XY medakas remained unchanged. These results suggest that ATBC does not exhibit estrogenic activity, although it may have weak androgenic activity or no sexual hormone activity.
Assuntos
Oryzias , Poluentes Químicos da Água , Animais , Masculino , Feminino , Oryzias/genética , Oryzias/metabolismo , Aromatase/metabolismo , Diferenciação Sexual , Vitelogeninas/genética , Vitelogeninas/metabolismo , Poluentes Químicos da Água/toxicidade , Gônadas/metabolismo , Plastificantes/metabolismo , Biomarcadores/metabolismo , Hormônios Esteroides Gonadais/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Di(2-ethylhexyl) phthalate (DEHP), the most widely used plasticizers in the world, has been regarded as an endocrine disrupting chemical with serious adverse health outcomes. Accumulating evidence strongly suggests that the undesirable biological effects of DEHP are meditated by its metabolites rather than itself. However, the metabolic footprints of DEHP in vivo are still unclear. Here we developed a click chemistry-assisted mass spectrometry (CC-MS) strategy for in-depth profiling DEHP metabolites in rats. An alkyne-modified DEHP analogue (alkyne-DEHP) was synthesized as a tracer for in vivo tracing, and a pair of MS probes (4-azido-nphenylbenzamide, 4-ANPA, and its deuterated reagent d5-4-ANPA) were prepared to specifically label the alkyne-DEHP metabolites, and prominently improve their detection sensitivity and selectivity. Using the CC-MS strategy, we successfully screened 247 alkyne-DEHP metabolites from rat urine, feces, and serum, including many unrevealed metabolites, such as oxidized phthalate diester metabolites and glucuronides of phthalate monoester metabolites. The discovery of new DEHP metabolites provides additional insights for understanding the metabolism of DEHP, which may be beneficial in exploring the mechanism underlying DEHP induced-toxicity in the future.