Confirmation of Di(2-ethylhexyl) phthalate-induced micronuclei by repeated dose liver micronucleus assay: focus on evaluation of liver micronucleus assay in young rats
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ABSTRACT:
SUBMITTER: Shigano M
PROVIDER: S-EPMC11344444 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Gordonia sp. strain P8219, a strain able to decompose di-2-ethylhexyl phthalate, was isolated from machine oil-contaminated soil. Mono-2-ethylhexyl phthalate hydrolase was purified from cell extracts of this strain. This enzyme was a 32,164-Da homodimeric protein, and it effectively hydrolyzed monophthalate esters, such as monoethyl, monobutyl, monohexyl, and mono-2-ethylhexyl phthalate. The K(m) and V(max) values for mono-2-ethylhexyl phthalate were 26.9 +/- 4.3 microM and 18.1 +/- 0.9 micromol/min . mg protein, respectively. The deduced amino acid sequence of the enzyme exhibited less than 30% homology with those of meta-cleavage hydrolases which are serine hydrolases but exhibited no significant homology with the sequences of serine esterases. The pentapeptide motif GXSXG, which is conserved in serine hydrolases, was present in the sequence. The enzymatic properties and features of the primary structure suggested that this enzyme is a novel enzyme belonging to an independent group of serine hydrolases.
| S-EPMC1449075 | biostudies-literature
Project description:The widespread use of plasticizers poses a serious threat to the environment and poultry health. Di-(2-ethylhexyl) phthalate (DEHP) is a commonly used plasticizer that can cause liver damage with prolonged exposure. Oxidative stress is closely associated with DEHP toxicity. Macrophage polarization plays an important role in many physiological and pathological processes and regulates disease development. This study aims to elucidate the mechanism of chronic DEHP exposure leading to chicken liver injury through oxidative stress-induced M1 polarization-necroptosis. In this study, the DEHP exposure model of chicken liver and the single and co-culture model of LMH and HD11 cells were established. With increasing dose and time, DEHP decreased body weight, increased liver coefficient, raised activities of liver function indicators and caused pathological liver damage in chickens. Further studies revealed the increase of reactive oxygen species (ROS) level and malonaldehyde (MDA) content, and the decrease of total antioxidant capacity (T-AOC) level, total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) activities, which led to excessive oxidative stress in the liver. In addition, there was increased infiltration of liver macrophages (CD68), upregulation of M1 polarization indicators (CD86, iNOS, IL-1β, TNF-α) and downregulation of M2 polarization indicators (CD163, Arg-1, IL-10, TGF-β) and appearance of necroptosis (RIPK1, RIPK3, MLKL). The vitro experiments confirmed the addition of N-acetylcysteine (NAC) inhibited M1 polarization and necroptosis. Besides, M1 polarization of HD11 cells promoted necroptosis of LMH cells in the HD11-LMH co-culture system. In brief, ROS-mediated M1 polarization-necroptosis is involved in DEHP-induced liver injury. This study provides a reference for environmental toxicant exposure in livestock and poultry farming.
| S-EPMC11665341 | biostudies-literature
Project description:Di (2-ethylhexyl) phthalate (DEHP) is a common plasticizer. Studies have revealed that DEHP exposure can cause liver damage. Green tea is one of the most popular beverages in China. Green tea polyphenols (GTPs) have been proven to have therapeutic effects on organ damage induced by heavy metal exposure. However, few study report on GTP relieving DEHP-induced liver damage.
2023-10-03 | GSE232128 | GEO
Project description:Allergic rhinitis (AR) is a common chronic inflammatory disease of the upper respiratory tract. Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer and belongs to environmental endocrine disruptors (EDCs). It can be entered the human body which is harmful to health. The relationship between DEHP and AR is still inconclusive. This study aims to investigate the effect of environmental pollutants DEHP on AR. By examining DEHP metabolites in the urine of AR patients and building an AR model. 24 BALB/c mice were used as the study subjects, and ovalbumin (OVA) and DEHP (3 mg/kg/body) were used for intragastric administration. They were divided into control group, DEHP group, OVA group and OVA + DEHP group. Examination, behavioral scoring, inflammatory factor testing, oxidative stress testing, detection of aryl hydrocarbon receptor (AhR) and signaling pathways CYP1A1 and CYP1B1 related proteins and mRNA. The concentrations of 3 metabolites of DEHP (MEHHP, MEOHP, and MEHP) in urine of AR patients were higher. And HE-staining showed that for the control group, many chronic inflammatory cell infiltration and nasal mucosal destruction were observed in the OVA + DEHP group and were more severe than the OVA group. Allergic symptom scores were obtained from sneezing, scratching, number of scratching, and nose flow. The scores of the OVA group and the OVA + DEHP group were higher than 7 points. Serum ELISA and nasal mucosal oxidative stress tests are more serious in the OVA + DEHP group. The expression of AhR protein and its mRNA was increased in the DEHP group, OVA group and OVA + DEHP group. The OVA + DEHP group was more significant in the OVA group and DEHP group. And the mRNAs of the AhR-related signaling pathways CYP1A1 and CYP1B1 were also more prominent in the OVA + DEHP group. DEHP may aggravate its inflammatory response through the AhR pathway closely related to the environment. When combined with OVA, DEHP can further aggravate the OVA-induced nasal inflammatory response and make the nasal cavity have undergone severe changes, and many inflammatory cells have infiltrated. DEHP has shown an adjuvant effect, and the AhR-related signaling pathways CYP1A1 and CYP1B1 may be critical.
| S-EPMC7471965 | biostudies-literature
Project description:A growing number of studies point to reduced fertility upon chronic exposure to endocrine-disrupting chemicals (EDCs) such as phthalates and plasticizers. These toxins are ubiquitous and are often found in food and beverage containers, medical devices, as well as in common household and personal care items. Animal studies with EDCs, such as phthalates and bisphenol A have shown a dose-dependent decrease in fertility and embryo toxicity upon chronic exposure. However, limited research has been conducted on the acute effects of these EDCs on male fertility. Here we used a murine model to test the acute effects of four ubiquitous environmental toxins: bisphenol A (BPA), di-2-ethylhexyl phthalate (DEHP), diethyl phthalate (DEP), and dimethyl phthalate (DMP) on sperm fertilizing ability and pre-implantation embryo development. The most potent of these toxins, di-2-ethylhexyl phthalate (DEHP), was further evaluated for its effect on sperm ion channel activity, capacitation status, acrosome reaction and generation of reactive oxygen species (ROS). DEHP demonstrated a profound hazardous effect on sperm fertility by producing an altered capacitation profile, impairing the acrosome reaction, and, interestingly, also increasing ROS production. These results indicate that in addition to its known chronic impact on reproductive potential, DEHP also imposes acute and profound damage to spermatozoa, and thus, represents a significant risk to male fertility.
| S-EPMC7338605 | biostudies-literature
Project description:The purpose of this study was to determine the origin, presence, and fate of the endocrine disruptor di-ethylhexil phthalate (DEHP) during tequila production. For this, three tequila factories (small, medium, and large) were monitored. DEHP concentrations in water, agave, additives, lubricating greases, neoprene seals, and materials of each stage process were analyzed using gas chromatography/mass spectrometry. DEHP mass balances were performed to identify the processes with significant changes in the inputs/outputs. DEHP was detected in agave at up to 0.08 ± 0.03 mg kg-1, water 0.02 ± 0.01 mg kg-1, lubricant greases 131.05 ± 2.80 mg kg-1, and neoprene seals 369.11 ± 22.52 mg kg-1. Whereas, tequila produced in the large, medium, and small factories contained 0.05 ± 0.01, 0.24 ± 0.04, and 1.43 ± 0.48 mg kg-1 DEHP, respectively. Furthermore, in waste materials (vinasses and bagasse) released, 534.26 ± 349.02, 947.18 ± 65.84, and 5222.60 ± 2836.94 mg of DEHP was detected for every 1000 L of tequila produced. The most significant increase in DEHP occurred during the sugar extraction and distillation stages. Results demonstrate that main raw materials, such as agave and water, contain DEHP, but lubricant greases and neoprene seals are the major sources of DEHP contamination. Identification of the contamination sources can help the tequila industry to take actions to reduce it, protect consumer health and the environment, and prevent circular contamination.
| S-EPMC10814815 | biostudies-literature
Project description:Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer found in a variety of polyvinyl chloride (PVC) medical products. The results of studies in experimental animals suggest that DEHP leached from flexible PVC tubing may cause health problems in some patient populations. While the cancerogenic and reproductive effects of DEHP are well recognized, little is known about the potential adverse impact of phthalates on the heart. This study examined the effects of clinically relevant concentrations of DEHP on neonatal rat cardiomyocytes. It was found that application of DEHP to a confluent, synchronously beating cardiac cell network, leads to a marked, concentration-dependent decrease in conduction velocity and asynchronous cell beating. The mechanism behind these changes was a loss of gap junctional connexin-43, documented using Western blot analysis, dye-transfer assay and immunofluorescence. In addition to its effect on electrical coupling, DEHP treatment also affected the mechanical movement of myocyte layers. The latter was linked to the decreased stiffness of the underlying fibroblasts, as the amount of triton-insoluble vimentin was significantly decreased in DEHP-treated samples. The data indicate that DEHP, in clinically relevant concentrations, can impair the electrical and mechanical behavior of a cardiac cell network. Applicability of these findings to human patients remains to be established.
| S-EPMC2670944 | biostudies-other
Project description:The brain and spinal cord have a limited capacity for self-repair under damaged conditions. One of the best options to overcome these limitations involves the use of phytochemicals as potential therapeutic agents. In this study, we have aimed to investigate the effects of di-(2-ethylhexyl) phthalate (DEHP) on hippocampus-derived neural stem cells (NSCs) proliferation to search phytochemical candidates for possible treatment of neurological diseases using endogenous capacity. In this experimental study, neonatal rat hippocampus-derived NSCs were cultured and treated with various concentrations of DEHP (0, 100, 200, 400 and 600 µM) and Cirsium vulgare (C. vulgare) hydroethanolic extract (0, 200, 400, 600, 800 and 1000 µg/ml) for 48 hours under in vitro conditions. Cell proliferation rates and quantitative Sox2 gene expression were evaluated using MTT assay and real-time reverse transcription polymerase chain reaction (RT-PCR). We observed the highest average growth rate in the 400 µM DEHP and 800 µg/ml C. vulgare extract treated groups. Sox2 expression in the DEHP-treated NSCs significantly increased compared to the control group. Gas chromatography/mass spectrometry (GC/ MS) results demonstrated that the active ingredients that naturally occurred in the C. vulgare hydroethanolic extract were 2-ethyl-1-hexanamine, n-heptacosane, 1-cyclopentanecarboxylic acid, 1-heptadecanamine, 2,6-octadien-1-ol,2,6,10,14,18,22-tetracosahexaene, and DEHP. DEHP profoundly stimulated NSCs proliferation through Sox2 gene overexpression. These results provide and opportunity for further use of the C. vulgure phytochemicals for prevention and/or treatment of neurological diseases via phytochemical mediated-proliferation of endogenous adult NSCs.
| S-EPMC5241513 | biostudies-literature
Project description:Di-(2-ethylhexyl) phthalate (DEHP) has been widely used in polyvinyl chloride products and has become ubiquitous in the developed countries. DEHP reportedly displays an adjuvant effect on immunoglobulin production. However, it has not been elucidated whether DEHP is associated with the aggravation of atopic dermatitis. We investigated the effects of DEHP on atopic dermatitis-like skin lesions induced by mite allergen in NC/Nga mice. NC/Nga male mice were injected intradermally with mite allergen on their right ears. In the presence of allergen, DEHP (0, 0.8, 4, 20, or 100 microg) was administered by intraperitoneal injection. We evaluated clinical scores, ear thickening, histologic findings, and the protein expression of chemokines. Exposure to DEHP at a dose of 0.8-20 microg caused deterioration of atopic dermatitis-like skin lesions related to mite allergen; this was evident from macroscopic and microscopic examinations. Furthermore, these changes were consistent with the protein expression of proinflammatory molecules such as macrophage inflammatory protein-1alpha (MIP-1alpha) and eotaxin in the ear tissue in overall trend. In contrast, 100 microg DEHP did not show the enhancing effects. These results indicate that DEHP enhances atopic dermatitis-like skin lesions at hundred-fold lower levels than the no observed adverse effect level determined on histologic changes in the liver of rodents. DEHP could be at least partly responsible for the recent increase in atopic dermatitis.
| S-EPMC1552025 | biostudies-literature
Project description:BackgroundDi(2-ethylhexyl) phthalate (DEHP), used primarily as a plasticizer for polyvinyl chloride, is found in a variety of products. Previous studies have quantified human exposure by back calculating intakes based on DEHP metabolite concentrations in urine and by determining concentrations of DEHP in exposure media (e.g., air, food, dust).ObjectivesTo better understand the timing and extent of DEHP exposure, we used a simple pharmacokinetic model to "reconstruct" the DEHP dose responsible for the presence of DEHP metabolites in urine.MethodsWe analyzed urine samples from eight adults for four DEHP metabolites [mono(2-ethylhexyl) phthalate, mono(2-ethyl-5-hydroxyhexyl) phthalate, mono(2-ethyl-5-oxohexyl) phthalate, and mono(2-ethyl-5-carboxypentyl) phthalate]. Participants provided full volumes of all voids over 1 week and recorded the time of each void and information on diet, driving, and outdoor activities. Using a model previously calibrated on a single person self-dosed with DEHP in conjunction with the eight participants' data, we used a simple trial-and-error method to determine times and doses of DEHP that resulted in a best fit of predicted and observed urinary concentrations of the metabolites.ResultsThe average daily mean and median reconstructed DEHP doses were 10.9 and 5.0 µg/kg-day, respectively. The highest single modeled dose of 60 µg/kg occurred when one study participant reported consuming coffee and a bagel with egg and sausage that was purchased at a gas station. About two-thirds of all modeled intake events occurred near the time of reported food or beverage consumption. Twenty percent of the modeled DEHP exposure occurred between 2200 hours and 0500 hours.ConclusionsDose reconstruction using pharmacokinetic models-in conjunction with biomonitoring data, diary information, and other related data-can provide a powerful means to define timing, magnitude, and possible sources of exposure to a given contaminant.
| S-EPMC3548287 | biostudies-literature