-
Foods (Basel, Switzerland) May 2024In this study, a novel magnetic molecularly imprinted polymeric material (FeO@MOF@MIP-160) with a metal-organic backbone (FeO@MOF) carrier was prepared using dibutyl...
In this study, a novel magnetic molecularly imprinted polymeric material (FeO@MOF@MIP-160) with a metal-organic backbone (FeO@MOF) carrier was prepared using dibutyl phthalate (DBP) as a template. The material can be used for the efficient, rapid, and selective extraction of trace amounts of phthalic acid esters (PAEs) in food and can detect them via gas chromatography-mass spectrometry (GC-MS). The synthesis conditions of the materials were optimized to prepare the FeO@MOF@MIP160 with the highest adsorption performance. Transmission electron microscopy (TEM), Fourier Transform Infrared Spectra (FT-IR), Vibration Sample Magnetic (VSM), and the Brunauer-Emmett-Teller (BET) method were used to characterize the materials. Compared with FeO@MOF and the magnetic non-imprinted polymeric material (FeO@MOF@NIP), FeO@MOF@MIP-160 possesses the advantages of easy and rapid manipulation of magnetic materials, the advantages of high specific surface area and the stability of metal-organic frameworks, and the advantages of high selectivity of molecularly imprinted polymers. FeO@MOF@MIP-160 has good recognition and adsorption capacity for di-butyl phthalate (DBP) and diethylhexyl phthalate (DEHP): the adsorption capacity for DBP and DEHP is 260 mg·g and 240.2 mg·g, and the adsorption rate is fast (reaching equilibrium in about 20 min). Additionally, FeO@MOF@MIP160 could be recycled six times, making it cost-effective, easy to operate, and time-saving as compared to traditional solid-phase extraction materials. The phthalate ester content in drinking water, fruit juice, and white wine was analyzed, with recoveries ranging from 70.3% to 100.7%. This proved that FeO@MOF@MIP160 was suitable for detecting and removing PAEs from food matrices.
PubMed: 38731768
DOI: 10.3390/foods13091397 -
BioRxiv : the Preprint Server For... Apr 2024Global and site-specific changes in DNA methylation and gene expression are associated with cardiovascular aging and disease, but how toxicant exposures during early...
BACKGROUND
Global and site-specific changes in DNA methylation and gene expression are associated with cardiovascular aging and disease, but how toxicant exposures during early development influence the normal trajectory of these age-related molecular changes, and whether there are sex differences, has not yet been investigated.
OBJECTIVES
We used an established mouse model of developmental exposures to investigate the effects of perinatal exposure to either lead (Pb) or diethylhexyl phthalate (DEHP), two ubiquitous environmental contaminants strongly associated with CVD, on age-related cardiac DNA methylation and gene expression.
METHODS
Dams were randomly assigned to receive human physiologically relevant levels of Pb (32 ppm in water), DEHP (25 mg/kg chow), or control water and chow. Exposures started two weeks prior to mating and continued until weaning at postnatal day 21 (3 weeks of age). Approximately one male and one female offspring per litter were followed to 3 weeks, 5 months, or 10 months of age, at which time whole hearts were collected (n ≥ 5 per sex per exposure). Enhanced reduced representation bisulfite sequencing (ERRBS) was used to assess the cardiac DNA methylome at 3 weeks and 10 months, and RNA-seq was conducted at all 3 time points. MethylSig and edgeR were used to identify age-related differentially methylated regions (DMRs) and differentially expressed genes (DEGs), respectively, within each sex and exposure group. Cell type deconvolution of bulk RNA-seq data was conducted using the MuSiC algorithm and publicly available single cell RNA-seq data.
RESULTS
Thousands of DMRs and hundreds of DEGs were identified in control, DEHP, and Pb-exposed hearts across time between 3 weeks and 10 months of age. A closer look at the genes and pathways showing differential DNA methylation revealed that the majority were unique to each sex and exposure group. Overall, pathways governing development and differentiation were most frequently altered with age in all conditions. A small number of genes in each group showed significant changes in DNA methylation and gene expression with age, including several that were altered by both toxicants but were unchanged in control. We also observed subtle, but significant changes in the proportion of several cell types due to age, sex, and developmental exposure.
DISCUSSION
Together these data show that perinatal Pb or DEHP exposures deflect normal age-related gene expression, DNA methylation programs, and cellular composition across the life course, long after cessation of exposure, and highlight potential biomarkers of developmental toxicant exposures. Further studies are needed to investigate how these epigenetic and transcriptional changes impact cardiovascular health across the life course.
PubMed: 38712146
DOI: 10.1101/2024.04.25.591125 -
Ecotoxicology and Environmental Safety Jun 2024Prenatal exposure to diethylhexyl phthalate (DEHP) has been linked with a decline in testosterone levels in adult male rats, but the underlying mechanism remains...
Prenatal exposure to diethylhexyl phthalate (DEHP) has been linked with a decline in testosterone levels in adult male rats, but the underlying mechanism remains unclear. We investigated the potential epigenetic regulation, particularly focusing on N6-methyladenosine (m6A) modification, as a possible mechanism. Dams were gavaged with DEHP (0, 10, 100, and 750 mg/kg/day) from gestational day 14 to day 21. The male offspring were examined at the age of 56 days. Prenatal DEHP administration at 750 mg/kg/day caused a decline in testosterone concentrations, an elevation in follicle-stimulating hormone, a downregulated expression of CYP11A1 HSD3B2, without affecting Leydig cell numbers. Interestingly, Methyltransferase Like 4 (METTL4), an m6A methyltransferase, was downregulated, while there were no changes in METTL3 and METTL14. Moreover, CYP11A1 showed m6A reduction in response to prenatal DEHP exposure. Additionally, METTL4 expression increased postnatally, peaking in adulthood. Knockdown of METTL4 resulted in the downregulation of CYP11A1 and HSD3B2 and an increase in SCARB1 expression. Furthermore, the increase in autophagy protection in adult Leydig cells induced by prenatal DEHP exposure was not affected by 3-methyladenosine (3MA) treatment, indicating a potential protective role of autophagy in response to DEHP exposure. In conclusion, prenatal DEHP exposure reduces testosterone by downregulating CYP11A1 and HSD3B2 via m6A epigenetic regulation and induction of autophagy protection in adult Leydig cells as a response to DEHP exposure.
Topics: Animals; Female; Male; Pregnancy; Rats; Adenosine; Cholesterol Side-Chain Cleavage Enzyme; Diethylhexyl Phthalate; Down-Regulation; Epigenesis, Genetic; Leydig Cells; Methyltransferases; Prenatal Exposure Delayed Effects; Rats, Sprague-Dawley; Testosterone
PubMed: 38678792
DOI: 10.1016/j.ecoenv.2024.116391 -
Nutrients Apr 2024Probiotics may protect against asthma. We want to investigate whether probiotics can reverse the adverse effects of phthalate exposure on asthma. We selected the female...
Probiotics may protect against asthma. We want to investigate whether probiotics can reverse the adverse effects of phthalate exposure on asthma. We selected the female offspring of BALB/c mice, born from pregnant female mice fed with diethylhexyl phthalate (DEHP). They were continuously administrated DEHP and ssp. SA-03 when they were 5 weeks old, and ovalbumin (OVA) for asthma induction started at 6 weeks for 32 days. The mice were divided into four groups ( = 6/group): 1. control group (C), 2. OVA/DEHP group (OD), 3. OVA/DEHP/probiotics low-dose group (ODP-1X), and OVA/DEHP/probiotics high-dose group (ODP-5X). We found that the administration of probiotics significantly reduced the asthma severity of the mice, as well as serum IgE and IL-5. In the ODP-5X group, the proportion of CD4+ cells in the lung was reduced, whereas IL-10 in serum and CD8+ cells in BALF were increased. In histopathology, the ODP group showed reduced infiltration of inflammatory cells, bronchial epithelial cell hyperplasia, and tracheal mucus secretion. These results might indicate that high-dose probiotics may affect anti-inflammatory cytokines and reduce asthma-relative indicators. The above results may provide evidence that high-dose probiotics supplementation might play a modulating role in DEHP causes of allergic asthma in the pediatric animal model.
Topics: Animals; Asthma; Mice, Inbred BALB C; Probiotics; Female; Mice; Ovalbumin; Ligilactobacillus salivarius; Diethylhexyl Phthalate; Disease Models, Animal; Pregnancy; Lung; Dietary Supplements; Immunoglobulin E; Bronchoalveolar Lavage Fluid
PubMed: 38674852
DOI: 10.3390/nu16081160 -
Ecotoxicology and Environmental Safety Jun 2024Mono-2-ethylhexyl phthalic acid (MEHP) is the most toxic metabolite of the plasticizer di-2-ethylhexyl phthalic acid (DEHP), and studies have shown that MEHP causes...
Mono-2-ethylhexyl phthalic acid (MEHP) is the most toxic metabolite of the plasticizer di-2-ethylhexyl phthalic acid (DEHP), and studies have shown that MEHP causes serious reproductive effects. However, its exact mechanisms of action remain elusive. In this study, we aimed to investigate the reproductive effects of MEHP and preliminarily explore its underlying molecular mechanisms. We found that TM3 cells gradually secreted less testosterone and intracellular free cholesterol with increasing MEHP exposure. MEHP exposure inhibited lipophagy and the Sirt1/Foxo1/Rab7 signaling pathway in TM3 cells, causing aberrant accumulation of intracellular lipid droplets. Addition of the Sirt1 agonist SRT1720 and Rab7 agonist ML-098 alleviated the inhibition of lipophagy and increased free cholesterol and testosterone contents in TM3 cells. SRT1720 alleviated the inhibitory effect of MEHP on the Sirt1/Foxo1/Rab7 signaling pathway, whereas ML-098 only alleviated the inhibition of Rab7 protein expression by MEHP and had no effect on Sirt1 and Foxo1 protein expression. This suggests that MEHP inhibits lipophagy in TM3 cells by suppressing the Sirt1/Foxo1/Rab7 signaling pathway, ultimately leading to a further decrease in cellular testosterone secretion. This study improves our current understanding of the toxicity and molecular mechanisms of action of MEHP and provides new insights into the reproductive effects of phthalic acid esters.
Topics: Testosterone; Sirtuin 1; Signal Transduction; Animals; Mice; rab7 GTP-Binding Proteins; Diethylhexyl Phthalate; Cell Line; rab GTP-Binding Proteins; Forkhead Box Protein O1; Plasticizers; Cholesterol
PubMed: 38663197
DOI: 10.1016/j.ecoenv.2024.116394 -
Ecotoxicology and Environmental Safety May 2024Di-hexyl phthalate (2-ethylhexyl) (DEHP) has been confirmed to cause female reproductive toxicity in humans and model animals by affecting the survival of ovarian...
A novel perspective on di-hexyl phthalate (2-ethylhexyl)-induced reproductive toxicity in females: Lipopolysaccharide synergizes with mono-2-ethylhexyl ester to cause inflammatory apoptosis rather than autophagy in ovarian granulosa cells.
Di-hexyl phthalate (2-ethylhexyl) (DEHP) has been confirmed to cause female reproductive toxicity in humans and model animals by affecting the survival of ovarian granulosa cells (GCs), but the interrelationships between DEHP's on autophagy, apoptosis, and inflammation in GCs are not clear. Our previous study demonstrated that DEHP exposure resulted in the disturbance of intestinal flora associated with serum LPS release, which in turn led to impaired ovarian function. LPS has also been shown to determine cell fate by modulating cellular autophagy, apoptosis, and inflammation. Therefore, this study investigated the role and link between LPS and autophagy, apoptosis, and inflammation of GCs in DEHP-induced ovarian injury. Here, we constructed an in vivo injury model by continuous gavage of 0-1500 mg/kg of DEHP in female mice for 30 days and an in vitro injury model by treatment of human ovarian granulosa cells (KGN) cells with mono-2- ethylhexyl ester (MEHP, an active metabolite of DEHP in vivo). In addition, the expression of relevant pathway molecules was detected by immunohistochemistry, immunofluorescence, qRT-PCR, and Western blotting after the addition of the autophagy inhibitor 3-methyladenine (3-MA), the apoptosis inhibitor Z-VAD- FMK and the NF-κB inhibitor BAY11-7082. The current study found that autophagy and apoptosis were significantly activated in GCs of DEHP-induced atretic follicles in vivo and found that MEHP-induced KGN cells autophagy and apoptosis were independent and potentially cytotoxic of each other in vitro. Further studies confirmed that DEHP exposure resulted in LPS release from the intestinal tract and entering the ovary, thereby participating in DEHP-induced inflammation of GCs. In addition, we found that exogenous LPS synergized with MEHP could activate the NF-κB signaling pathway to induce inflammation and apoptosis of GCs in a relatively prolonged exposure condition. Meanwhile, inhibition of inflammatory activation could rescue apoptosis and estrogen secretion function of GCs induced by MEHP combined with LPS. These results indicated that the increased LPS influenced by DEHP might cooperate with MEHP to induce inflammatory apoptosis of GCs, an important cause of ovarian injury in mice.
Topics: Female; Animals; Diethylhexyl Phthalate; Autophagy; Granulosa Cells; Lipopolysaccharides; Apoptosis; Mice; Inflammation; Reproduction; Humans
PubMed: 38615642
DOI: 10.1016/j.ecoenv.2024.116319 -
Biomedical and Environmental Sciences :... Mar 2024
Topics: Humans; Female; Rats; Animals; Male; Genistein; Lipid Metabolism; Diethylhexyl Phthalate; Maternal Exposure; Prenatal Exposure Delayed Effects
PubMed: 38582995
DOI: 10.3967/bes2024.034 -
Scientific Reports Apr 2024In recent years, the presence and migration of PAEs in packaging materials and consumer products has become a serious concern. Based on this concern, the aim of our...
In recent years, the presence and migration of PAEs in packaging materials and consumer products has become a serious concern. Based on this concern, the aim of our study is to determine the possible migration potential and speed of PAEs in benthic fish stored in vacuum packaging, as well as to monitor the storage time and type as well as polyethylene (PE) polymer detection.As a result of the analysis performed by µ-Raman spectroscopy, 1 microplastic (MP) of 6 µm in size was determined on the 30th day of storage in whiting fish muscle and the polymer type was found to be Polyethylene (PE) (low density polyethylene: LDPE). Depending on the storage time of the packaging used in the vacuum packaging process, it has been determined that its chemical composition is affected by temperature and different types of polymers are formed. 10 types of PAEs were identified in the packaging material and stored flesh fish: DIBP, DBP, DPENP, DHEXP, BBP, DEHP, DCHP, DNOP, DINP and DDP. While the most dominant PAEs in the packaging material were determined as DEHP, the most dominant PAEs in fish meat were recorded as BBP and the lowest as DMP. The findings provide a motivating model for monitoring the presence and migration of PAEs in foods, while filling an important gap in maintaining a safe food chain.
Topics: Animals; Diethylhexyl Phthalate; Plastics; Vacuum; Phthalic Acids; Polyethylene; Polymers; Dibutyl Phthalate; Esters; China
PubMed: 38575598
DOI: 10.1038/s41598-024-54730-5 -
ACS Applied Materials & Interfaces Apr 2024Changes in diet culture and modern lifestyle contributed to a higher incidence of gastrointestinal-related diseases, including gastritis, implicated in the pathogenesis...
Changes in diet culture and modern lifestyle contributed to a higher incidence of gastrointestinal-related diseases, including gastritis, implicated in the pathogenesis of gastric cancer. This observation raised concerns regarding exposure to di(2-ethylhexyl) phthalate (DEHP), which is linked to adverse health effects, including reproductive and developmental problems, inflammatory response, and invasive adenocarcinoma. Research on the direct link between DEHP and gastric cancer is ongoing, and further studies are required to establish a conclusive association. In our study, extremely low concentrations of DEHP exerted significant effects on cell migration by promoting the epithelial-mesenchymal transition in gastric cancer cells. This effect was mediated by the modulation of the PI3K/AKT/mTOR and Smad2 signaling pathways. To address the DEHP challenges, our initial design of TPGS-conjugated fucoidan, delivered via pH-responsive nanoparticles, successfully demonstrated binding to the P-selectin protein. This achievement has not only enhanced the antigastric tumor efficacy but has also led to a significant reduction in the expression of malignant proteins associated with the condition. These findings underscore the promising clinical therapeutic potential of our approach.
Topics: Humans; Diethylhexyl Phthalate; Plasticizers; Stomach Neoplasms; Phosphatidylinositol 3-Kinases; Phthalic Acids
PubMed: 38574184
DOI: 10.1021/acsami.3c15976 -
Ecotoxicology and Environmental Safety Apr 2024Phthalates are widely used plasticizers, which were identified as risk factors in the development of many human diseases. However, the effects of phthalates in the...
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.
Topics: Adult; Humans; Animals; Mice; Middle Aged; Aged; Aged, 80 and over; Environmental Exposure; Diethylhexyl Phthalate; Phthalic Acids; Periodontitis; Inflammation; Environmental Pollutants
PubMed: 38547731
DOI: 10.1016/j.ecoenv.2024.116252