Search Results (211)

Di(2-ethylhexyl) phthalate (DEHP), a widely employed exogenous plasticizer, has become pervasive in the environment and living organisms due to its extensive use in food packaging, medical devices, and daily consumer products, and is established as a typical endocrine-disrupting chemical. Growing evidence indicates a strong association between DEHP exposure and the incidence of chronic bone disorders, including osteoporosis (OP), osteoarthritis (OA), and osteonecrosis of the femoral head (ONFH). However, the molecular mechanisms underlying its pathogenic effects across these diseases remain poorly defined. In this study, we applied an environmental network toxicology approach to integrate predicted protein targets of DEHP with known disease-associated targets of the three bone disorders using multiple databases. Through Venn analysis, protein–protein interaction (PPI) network construction, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, we identified core targets and key signaling pathways. Molecular docking and molecular dynamics (MD) simulations were further employed to validate the binding modes and stability between DEHP and the core targets, thereby elucidating common and distinct mechanisms of DEHP across these bone diseases. A total of 109 overlapping targets of DEHP and the three bone diseases were identified, among which 7 core targets—AKT1, SRC, ESR1, CASP3, MMP9, BCL2, and BCL2L1—were common to all three disorders. These are implicated in critical biological processes such as apoptosis regulation, inflammation, extracellular matrix degradation, and estrogen signaling. KEGG enrichment analysis revealed significant involvement of the PI3K-Akt, MAPK, Ras, TNF, and estrogen signaling pathways across all three diseases. Molecular docking and MD simulations confirmed stable binding of DEHP to key targets including AKT1, ESR1, and MMP9, supporting its potential to disrupt bone metabolic homeostasis via multi-target and multi-pathway mechanisms. Further analysis indicated that DEHP exerts both shared and disease-specific effects: it disrupts osteoblast/osteoclast balance in OP, amplifies inflammatory responses and matrix degradation in OA, and contributes to impaired angiogenesis and osteocyte necrosis in ONFH. This study systematically reveals how DEHP disrupts bone homeostasis through a multi-target and multi-pathway network, constructing a cross-disease osteotoxicity framework. It is the first to delineate the common and distinct molecular mechanisms of DEHP in OP, OA, and ONFH. Although these insights are derived from computational models and require further experimental validation, they provide a novel theoretical basis for combined intervention strategies targeting multiple bone diseases and for environmental health risk assessment. Full article

Diethylhexyl phthalate (DEHP), a common environmental plasticizer, induces oxidative damage and cell apoptosis without efficient treatment. Tremella fuciformis polysaccharides (TFPs) are known natural antioxidants, yet their protection against DEHP toxicity remains unclear. This study aimed to investigate the protective effects of TFP against DEHP-induced toxicity using both human umbilical vein endothelial cells (HUVECs) and Caenorhabditis elegans models. The results demonstrate that TFPs significantly alleviated DEHP-induced cytotoxicity in HUVECs by reducing reactive oxygen species (ROS) generation and inhibiting mitochondrial apoptosis pathways, which may contribute to the activation of antioxidant systems mediating via Nrf-2. In C. elegans, TFP improved survival rates under DEHP stress and reduced ROS accumulation. This protection was associated with the modulation of the insulin-like pathway and skn-1 gene to increase the expressions of antioxidant genes. Our findings reveal that TFP exhibits protection against DEHP-induced oxidative stress and apoptosis through the synergistic regulation of survival and antioxidant pathways, highlighting its potential as a natural dietary intervention for environmental toxicant-induced health risks. Full article

Mono(2-ethylhexyl) phthalate (MEHP), a bioactive metabolite of di(2-ethylhexyl) phthalate (DEHP), has been detected in the placenta and urine of pregnant women and is linked to adverse pregnancy outcomes. However, its effects on mitochondrial homeostasis in trophoblast cells remain incompletely understood. This study examined the impact of MEHP (0.5–200 µM) on mitochondrial function, dynamics, and biogenesis in human HTR-8/SVneo trophoblast cells. MEHP (≥5 µM) reduced MTT conversion without compromising membrane integrity, suggesting early metabolic or redox imbalance. A dose-dependent loss of mitochondrial membrane potential was observed, with increased reactive oxygen species (ROS) generation only at 200 µM. MEHP modulated the expression of mitochondrial dynamics genes, with a more pronounced mitofusin 1 (MFN1) induction at low doses and increased mitochondrial DNA content, suggesting a compensatory response to mild stress. Conversely, high doses more strongly induced fission and mitochondrial 1 (FIS1) expression, suggesting mitochondrial fragmentation. Both concentrations induced the expression of the mitochondrial biogenesis regulators peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) and nuclear factor erythroid 2–related factor 2 (Nrf2), while sirtuin 1 (SIRT1) expression and activity declined progressively with dose. These results demonstrate that MEHP disrupts mitochondrial homeostasis in trophoblast cells at concentrations spanning the estimated human exposure range. The dose-dependent effects, from adaptive responses to overt dysfunction, may help explain the associations between MEHP exposure and placental pathology observed in epidemiological studies. Full article

Phthalates are widely used plasticizers recognized as endocrine-disrupting chemicals (EDCs) with well-documented adverse effects on reproductive health. These compounds act either directly or through their metabolites and can influence various biochemical pathways. Key phthalates that have been associated with potential toxic outcomes include di(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), butyl benzyl phthalate (BBP), diisononyl phthalate (DiNP), and diisodecyl phthalate (DiDP). The presence of these compounds in everyday consumer products has been associated with various adverse effects on human reproductive health, including hormonal disruption, issues in gonadal function, and other hormone related problems. This systematic review provides an overview and critical synthesis of the most recent research regarding phthalate reproductive toxicity. The scope is to summarize and aggregate correlations between phthalate exposure and reproductive health outcomes and highlight factors, such as age, sex, and extent of exposure, that have the most significant impacts on clinical outcomes. The reported studies focus on the gender-specific outcomes of various phthalates, while the epidemiological data reveal the importance of exposure duration and age. The reported results highlight the need for strict regulations regarding phthalate usage and the importance of developing safer alternatives. Full article

Phthalic acid esters (PAEs), ubiquitously employed as a plasticizer, have been classified as priority environmental pollutants because of their persistence, bioaccumulation, and endocrine-disrupting properties. As a characterized PAE-degrading strain of marine origin, Mycolicibacterium phocaicum RL-HY01 utilizes di-(2-ethylhexyl) phthalate (DEHP) as its sole carbon and energy source. Genome sequencing and RT-qPCR analysis revealed a previously uncharacterized hydrolase gene (dehpH) in strain RL-HY01, which catalyzes ester bond cleavage in PAEs. Subsequently, recombinant expression of the cloned dehpH gene from strain RL-HY01 was established in Escherichia coli BL21(DE3). The purified recombinant DehpH exhibited optimal activity at 30 °C and pH 8.0. Its activity was enhanced by Co²⁺ and tolerant to most metal ions but strongly inhibited by EDTA, SDS, and PMSF. Organic solvents (Tween-80, Triton X-100, methanol, ethanol, isopropanol, acetone, acetonitrile, ethyl acetate, and n-hexane) showed minimal impact. Substrate specificity assay indicated that DehpH could efficiently degrade the short and long side-chain PAEs but failed to hydrolyze the cyclic side-chain PAE (DCHP). The kinetics parameters for the hydrolysis of DEHP were determined under the optimized conditions, and DehpH had a V_max of 0.047 ± 0.002 μmol/L/min, K_m of 462 ± 50 μmol/L, and k_cat of 3.07 s⁻¹. Computational prediction through structural modeling and docking identified the active site, with mutagenesis studies confirming Ser228, Asp324, and His354 as functionally indispensable residues forming the catalytic triad. The identification and characterization of DehpH provided novel insights into the mechanism of DEHP biodegradation and might promote the application of the target enzyme. Full article

Male infertility, as a globally significant reproductive health issue, remains idiopathic in over 40% of cases. Reproductive disorders in males induced by environmental pollutants, such as di(2-ethylhexyl) phthalate (DEHP), have garnered considerable attention in recent years. DEHP induces testicular oxidative stress and ferroptosis via its active metabolite MEHP, thereby leading to spermatogenic dysfunction. Lycium barbarum polysaccharide (LBP), a traditional food and medicine homologous substance, exhibits potential antioxidant and reproductive protective properties. However, the underlying mechanism by which LBP intervenes in the toxicity induced by DEHP remains to be elucidated. This study explored the protective effect and molecular mechanism of LBP on DEHP-induced testicular injury through in vivo and in vitro experiments. The result showed that DEHP exposure (150 mg/L in free drinking water for 6 weeks) significantly decreased testicular weight, sperm concentration, and sperm motility in mice, while DEHP exposure induced pathological damage to testicular tissue, as evidenced by cavitation of seminiferous tubules, reduced numbers of spermatocytes, and vacuolar degeneration of Sertoli cells. However, LBP (450 mg/L) treatment significantly reversed testicular damage and sperm parameters. In vitro, MEHP reduced the viability of GC2 cells (spermatocyte cell line) and TM4 cells (Sertoli cell line), and LBP significantly restored cell activity. Mechanistically, exposure to DEHP/MEHP results in iron overload (elevated levels of free Fe²⁺), lipid peroxidation (increased MDA and reduced GSH), and dysregulated expression of key proteins involved in ferroptosis and iron homeostasis within the testis and cells. Furthermore, it was demonstrated that when NRF2 was specifically inhibited by ML385 or silenced via siRNA, the protective effects of LBP were abrogated, thereby validating the critical role of NRF2 in the regulation of iron homeostasis by LBP. In conclusion, LBP mitigates DEHP-induced testicular injury by activating NRF2 to regulate iron homeostasis in Sertoli cells and spermatocytes cells. This study not only offers a potential strategy for the prevention and treatment of male reproductive disorders caused by DEHP exposure, but also underscores the reproductive protective effects and application prospects of LBP in this context. Full article

PET (polyethylene terephthalate) bottles contain different chemicals that can act as endocrine disruptors. Phthalates and bisphenol A can be found in various foods and beverages packaged in PET packaging or aluminum cans. For some phthalates, the European Union has established specified tolerable daily intakes for humans. This study aimed to establish the changes, types of phthalates (dimethyl phthalate, diethyl phthalate, diisobutyl phthalate, dibutyl phthalate, bis(2-ethylhexyl) phthalate, di-n-octyl phthalate), and bisphenol A concentrations in beer packaged in PET bottles and stored at two temperatures (4 °C and 20 °C) for four months. Beers were obtained from a local brewery after packaging into PET bottles and stored at the designated temperatures. GC-MS analysis was performed to determine phthalates and bisphenol A. Obtained data show that beers packaged in PET bottles can contain significant amounts of bisphenol A, and that their concentration increases with storage time. Phthalates were also identified in the samples, with the highest concentration of bis(2-ethylhexyl) phthalate found in the sample kept at 20 °C after 1 month of storage, sample P5; this concentration was 164.814 µg/L. BPA was recorded with the highest concentration in sample P11, which underwent 4 months of storage at a temperature of 20 °C. Full article

Although the risks of microplastics (MPs) and plasticizers have received attention, plastic chemical parks, as an important source of them, lack adequate research. A river in eastern China that connects to Hangzhou Bay and receives wastewater from the plastics industry was targeted for investigation. The highest concentrations of MPs in water and sediment samples were found at the effluent (2250 ± 469 items/L and 3245 ± 430 items/kg, respectively). The WWTP effluent significantly increased the concentrations of MPs in the downstream water and sediments, which were 2.77 and 2.57 times higher than those in the upstream water, respectively. It was estimated that 2.24 × 10¹³ MPs entered the environment annually through wastewater discharge. The di(2-ethylhexyl) phthalate (DEHP) concentration was the highest at the effluent (32.6 ± 7.9 μg/L in water and 2.7 ± 3.4 μg/g in sediment), and the downstream DEHP concentrations were 3.37 and 2.41 times higher than those in the upstream water and sediment, respectively. All three risk assessment models showed that the WWTP discharge outlet had the highest risk of MPs. DEHP in 87.5% of sediment samples posed a medium risk to algae. Full article

This study aimed to evaluate the presence of emerging pollutants [perfluorinated compounds, phthalates and bisphenol A (BPA)] in chinstrap penguins (Pygoscelis antarctica) and krill (Euphausia superba) from Deception Island (South Shetland Islands, Antarctica) to provide data on the occurrence of emerging pollutants in Antarctica. For this purpose, thirty-four samples were studied, including four samples of adult tissue and six samples of chick tissue, as well as krill samples from the area. The selected samples were subjected to extraction processes and subsequent analytical determination of perfluorooctane sulfonate, perfluorooctanoic acid, di(2-ethylhexyl) phthalate, mono(2-ethylhexyl) phthalate and BPA using high-performance liquid chromatography coupled with electrospray ionization mass spectrometry. Our results highlight that the analyzed organic pollutants, except for BPA, are clearly present in Pygoscelis antarctica and Euphausia superba from Deception Island. Full article

This study investigated the presence and concentration of selected phthalates in municipal tap waters and purified waters sourced from domestic water purifiers and municipal reverse osmosis-based supplies. Five target compounds: Diethyl phthalate (DEP), Diisobutyl phthalate (DiBP), Butyl octyl phthalate (BOP), Dibutyl phthalate (DBP), and bis(2-ethylhexyl) phthalate (DEHP) were identified and quantified in the samples using the solid-phase microextraction gas chromatography-mass spectrometry (SPME-GC/MS) method. The analytical protocol demonstrated good sensitivity, precision, and accuracy, with low limits of detection and quantification, making it suitable for routine monitoring applications. Phthalates were detected in all samples, including both inlet and treated water, highlighting their widespread occurrence. The results show a significant percentage of reduction in total phthalate concentrations (from 4% to 53%; 30% on average) in purified water samples compared to untreated inlet water, thereby indicating the potential efficacy of such systems in reducing organic pollutants. Risk assessment based on the EFSA guidelines showed that the estimated daily intakes for all detected phthalates remained well below tolerable daily intake limits for both adults and toddlers. The findings underscore the importance of monitoring phthalates in drinking water and support the implementation of regular maintenance strategies for filtration devices. The analytical approach developed may be adopted as a cost-effective tool for water quality assessment and offers promising potential for broader application in public health and commercial water treatment systems. Full article

Background/Objectives: Phthalates are endocrine-disrupting chemicals that are commonly used in plastic consumer products and food packaging, with growing evidence suggesting that they have a potential role in obesity. This study aimed to investigate the association between urinary concentrations of phthalate metabolites and both general and abdominal obesity among adult males in Spain. Methods: We analysed data from 1124 male participants of the Aragon Workers’ Health Study (AWHS) collected between 2011 and 2014 in Zaragoza, Spain. Eleven urinary phthalate metabolites were measured and adjusted for creatinine levels. Multivariate logistic regression models were used to evaluate associations between phthalate exposure and general and abdominal obesity, controlling for dietary and lifestyle factors. Dose–response relationships were explored using restricted cubic spline models. Results: Higher urinary concentrations of di(2-ethylhexyl) phthalate (∑DEHP) and two of its metabolites—mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP)—were significantly associated with general obesity. The adjusted odds ratios were: ∑DEHP [OR = 1.26; 95% CI: 1.01, 1.58], MEOHP [OR = 1.24; 95% CI: 1.00, 1.53], and MEHHP [OR = 1.26; 95% CI: 1.03, 1.55]. In contrast, mono-isobutyl phthalate (MiBP) was inversely associated with abdominal obesity [OR = 0.73; 95% CI: 0.57, 0.93]. Conclusions: These findings suggest a positive association between exposure to DEHP and its metabolites and general obesity. This highlights the potential importance of environmental exposures as modifiable factors in obesity prevention and supports the need for further investigation in nutritional and public health contexts. Full article

The widespread use of plastics has led to a substantial increase in plastic waste, resulting in the dissemination of plastic debris throughout ecosystems and posing significant threats to biota. Bis(2-ethylhexyl) phthalate (DEHP), a commonly used plasticizer, enhances plastic flexibility but may also exert subtle toxic effects. This study aimed to investigate the potential toxicological impacts and underlying mechanisms of microplastics (MPs), di-(2-ethylhexyl) phthalate (DEHP), and their combined exposure (MPs + DEHP) on oxidative stress, apoptotic damage, transcriptomic alterations, and metabolic disturbances in mice. The results demonstrated that exposure to MPs, DEHP, and MPs + DEHP impaired the antioxidant defense system and reduced overall antioxidant capacity. Concurrently, all three exposure conditions significantly increased biochemical markers, particularly those associated with liver dysfunction, prompting further analysis of hepatic tissues. Histopathological examination revealed apoptotic damage in hepatocytes. Integrated transcriptomic and metabolomic analyses indicated that exposure to MPs, DEHP, and MPs + DEHP disrupted carbohydrate, amino acid, and lipid metabolism, induced the expression of genes related to hepatocarcinogenesis, and impaired purine metabolism. Moreover, MP and DEHP exposure aggravated hepatic apoptosis and inflammatory responses via activation of the PI3K/AKT signaling pathway, thereby eliciting notable biotoxic effects. These findings provide new scientific evidence regarding the individual and combined toxicological effects of MPs and the plastic additive DEHP on living organisms. Full article

Pituitary adenomas, although predominantly benign, can lead to significant clinical complications due to endocrine imbalances and mass effects on adjacent structures. Traditional research has focused on intrinsic factors like genetic mutations and hormonal dysregulation; however, emerging evidence implicates environmental pollutants—particularly urban air contaminants—in pituitary tumorigenesis. This review consolidates current findings on how chronic exposure to pollutants such as benzene, di(2-ethylhexyl) phthalate (DEHP), and polychlorinated biphenyls (PCBs) may trigger neuroinflammation, disrupt the hypothalamic–pituitary–adrenal (HPA) axis, and alter pituitary cell proliferation and hormone secretion. We explore mechanistic pathways involving inflammatory cytokines, oxidative stress, and microenvironmental modifications that contribute to neoplastic transformation and tumor progression. Epidemiological studies, supported by in vitro experiments, suggest that air pollutants not only initiate the development of pituitary adenomas but may also enhance the secretory activity of functioning tumors, potentially increasing their aggressiveness. Given the escalating global burden of air pollution and its far-reaching public health implications, further investigation is essential to elucidate these complex interactions. Advancing our understanding in this area could inform preventive strategies and therapeutic interventions aimed at mitigating the environmental impact on pituitary tumor behavior. Full article

Phthalates are compounds widely used as very effective plasticizers of PVC. Unfortunately, they are also widely known to be endocrine disruptors and are detrimental to human health and the environment. For this reason, environmentally friendly plasticizers are being intensively sought after in response to the market needs in the context of sustainable development and legislative changes regarding the use of phthalates. Our research presents an innovative approach to addressing this problem. In this paper, we propose new biobased oligoesters as non-toxic and harmless plasticizers of poly(vinyl chloride). New plasticizers were obtained by polyesterification of saturated dimerized fatty acid (DFA), adipic acid (ADA), triethylene glycol (TEG), and 2-ethylhexanol (2-EH), and were characterized by nuclear magnetic resonance, size exclusion chromatography, and viscosity analyses. The compatibility of the obtained oligoesters with PVC was determined using the method for obtaining PVC films by casting from a THF solution. Selected plasticizers were used to obtain PVC blends at 50 phr. They were then tested for plasticizer migration, hardness, thermogravimetric analysis, differential scanning calorimetry, and mechanical strength. Their properties were compared with the commercially available monomeric plasticizers di(2-ethylhexyl) terephthalate and di(2-ethylhexyl) adipate. The conducted study shows that the oligoesters obtained at a molar ratio of ADA to DFA of 9:1 and using an excess of 2-EH exhibit very good compatibility and plasticizing ability. The use of higher amounts of DFA worsens the compatibility of the oligoesters with PVC. However, a 4:1 ADA-to-DFA molar ratio produced results that still allow for the use of these compounds as plasticizers at lower concentrations or in combination with other plasticizers. Full article

Pituitary cells are specialized cells located within the pituitary gland, a small, pea-sized gland situated at the base of the brain. Through the use of cellular electrophysiological techniques, the electrical properties of these cells have been revealed. This review paper aims to introduce the ion currents that are known to be functionally expressed in pituitary cells. These currents include a voltage-gated Na⁺ current (I_Na), erg-mediated K⁺ current (I_K(erg)), M-type K⁺ current (I_K(M)), hyperpolarization-activated cation current (I_h), and large-conductance Ca²⁺-activated K⁺ (BK_Ca) channel. The biophysical characteristics of the respective ion current were described. Additionally, we also provide explanations for the effect of various drugs or compounds on each of these currents. GH₃-cell exposure to GV-58 can increase the magnitude of I_Na with a concurrent rise in the inactivation time constant of the current. The presence of esaxerenone, an antagonist of the aldosterone receptor, directly suppresses the magnitude of peak and late I_Na. Risperidone, an atypical antipsychotic agent, is effective at suppressing the I_K(erg) amplitude directly, and di(2-ethylhexyl)-phthalate suppressed I_K(erg). Solifenacin and kynurenic acid can interact with the K_M channel to stimulate I_K(M), while carisbamate and cannabidiol inhibit the I_h amplitude activated by sustained hyperpolarization. Moreover, the presence of either rufinamide or QO-40 can enhance the activity of single BK_Ca channels. To summarize, alterations in ion currents within native pituitary cells or pituitary tumor cells can influence their functional activity, particularly in processes like stimulus–secretion coupling. The effects of small-molecule modulators, as demonstrated here, bear significance in clinical, therapeutic, and toxicological contexts. Full article