Evaluation of the Effects of Di-(2-ethylhexyl) phthalate (DEHP) on Caenorhabditis elegans Survival and Fertility.

Di-2-ethylhexyl (DEHP), which is widely used in industrial products, is produced annually in excess of 2 million tons worldwide. DEHP is an endocrine disruptor and one of the major environmental pollutant chemicals (EDCs) in nature. There is some information about the effects of these products, which provide great advantages in every respect, on human health and the environment. In this study, C. elegans organism was used to evaluate the health and environmental risks of DEHP. The survival and fertility effects of DEHP on the C. elegans organism were examined and the results were evaluated. In the study, it was determined that DEHP not only shortened the survival time of C. elegans but also caused a decrease in fertility. DEHP (0.625 mM and 10 mM) caused a 23.2-30.6% decrease in fertility. Additionally, the LC50 (50% lethal concentration) value of DEHP was found to be 321 µg/mL.

Occurrence and ecological risk assessment of 16 plasticizers in the rivers and estuaries in Japan.

Owing to growing concerns about the adverse effects of phthalate plasticizers, non-phthalate plasticizers are being increasingly used as their replacement. However, information on the residual environmental concentrations and ecological risks posed by these plasticizers is limited. In this study, we analyzed the environmental contamination of 11 phthalates and 5 non-phthalate plasticizers in Class A and B rivers in Japan. In the considered river water samples, phthalates and non-phthalates were detected in the following order of detection frequency: phthalates (DEHP > DMP > DMEP > BBP > DNPP > DNP > DEEP > DBEP = DNOP) and non-phthalates (ATBC > DEHS > DEHA > TOTM = DIBA). Phthalate plasticizers were the most abundant and included DEHP (157-859 ng/L), DMP (

Maternal Di-(2-ethylhexyl)-Phthalate exposure during pregnancy altered energy metabolism in immature offspring and caused hyperglycemia.

Di-(2-ethylhexyl)-phthalate (DEHP), as distinctive endocrine disrupting chemicals, has become a global environmental pollutant harmful to human and animal health. However, the impacts on offspring and mothers with maternal DEHP exposure are largely unknown and the mechanism remains elusive. We established DEHP-exposed maternal mice to investigate the impacts on mother and offspring and illustrate the mechanism from multiple perspectives. Pregnant mice were administered with different doses of DEHP, respectively. Metagenomic sequencing used fecal and transcriptome sequencing using placentas and livers from offspring have been performed, respectively. The results of the histopathology perspective demonstrated that DEHP exposure could disrupt the function of islets impact placentas and fetus development for maternal mice, and cause the disorder of glucose and lipid metabolism for immature offspring mice, resulting in hyperglycemia. The results of the metagenome of gut microbial communities indicated that the dysbiosis of gut microbiota in mother and offspring mice and the dominant phyla transformed through vertical transmission. Transcriptome analysis found DEHP exposure induced mutations of Ahcy and Gstp3, which can damage liver cells and affect the metabolism of the host. DEHP exposure harms pregnant mice and offspring by affecting gene expression and altering metabolism. Our results suggested that exposure of pregnant mice to DEHP during pregnancy and lactation increased the risk of metabolic disorders by altering key genes in liver and gut microbiota, and these results provided new insights into the potential long-term harms of DEHP.

Di (2-ethylhexyl) phthalate effects on the growth, development, and reproduction of Moina macrocopa (Crustacea: Cladocera).

Di (2-ethylhexyl) phthalate (DEHP) is used as a plasticizer in plastics. The effects of DEHP on terrestrial vertebrates have been extensively reported but the effects of DEHP contamination on aquatic ecosystems have not been thoroughly studied. Since water bodies are one of the main mediums through which DEHP is released worldwide, the impacts of DEHP contamination should be manifested in water fleas. Therefore, maternal Moina macrocopa were exposed to 1, 10, 100, and 1000 µg/L concentrations of DEHP. Changes in growth and reproduction were evaluated. The findings demonstrated that DEHP exposure did not have a negative impact on growth or the ability to reproduce. An analysis of the ovary yolk body (YB) demonstrated that the average size and number of yolk bodies (YBs) produced by M. macrocopa exposed to 1000 µg/L DEHP were not significantly different to the average size and number of YBs produced in blank control and solvent control conditions. These outcomes support the cellular pathology data gathered by other researchers. Nevertheless, when M. macrocopa was exposed to 1000 µg/L DEHP for five days, a significant increase in YB numbers was observed with changes in YB morphology. The critical cellular pathology of YB showed morphological abnormalities, including rod-shaped YBs, and YB density was higher than in the blank and solvent controls. Even though these results suggest that antioxidative stress can be induced by DEHP exposure, growth, and reproduction were not significantly different among exposed water fleas compared to fleas in the blank and solvent controls. The result was attributed to the antioxidant response of the water flea. In conclusion, the present study enhances our understanding of previous findings from risk assessments of DEHP contamination in aquatic ecosystems.

Prenatal DEHP exposure induces lifelong testicular toxicity by continuously interfering with steroidogenic gene expression.

Background: Epidemiologic studies suggested the association between prenatal di-(2-ethylhexyl) phthalate (DEHP) exposure and disorders of sex development (DSD), adult male disorders, and reproductive aging. Inhibiting testosterone synthesis by interfering with steroidogenic gene expression induces testicular toxicity, however, whether prenatal DEHP exposure induces testicular toxicity through this mechanism remains uncertain. Methods: C57BL/6JGpt male mice underwent different doses (0, 100, 500, 1,000 mg/kg) of prenatal DEHP exposure during gestational day 10 to delivery day, the testicular toxicity (genital development, testosterone, semen quality, and morphology of testis tissue) in the neonatal, post-puberal and middle-aged stages was observed, and the steroidogenic gene (Lhcgr, Star, Cyp11a1, Cyp17a1, Hsd17b3, and Hsd3b2) expression was analyzed by quantitative polymerase chain reaction (qPCR) and Western blot (WB). The interference of steroidogenic gene expression in TM3 cells after mono-(2-ethylhexyl) phthalate (MEHP) exposure was also explored for verification. Results: Prenatal DEHP exposure induced immediate testicular injury in the neonatal stage [reduced anogenital distance (AGD) and intratesticular testosterone], DSD in the post-puberal stage (poor genital development), and reproductive aging in the middle-aged stage (obesity, reduced testosterone and semen quality, and atrophic seminiferous tubules), especially in the high dose. Prenatal DEHP exposure continuously interfered with steroidogenic gene expression (Hsd3b2, Hsd17b3) in RNA and protein levels. MEHP inhibited testosterone synthesis of TM3 cells by interfering with steroidogenic gene expression (Hsd3b2, Hsd17b3) in RNA and protein levels. Conclusions: Prenatal DEHP exposure induces lifelong testicular toxicity by continuously interfering with steroidogenic gene expression, thus indicating the association between prenatal exposure and DSD, adult male disorders, and reproductive aging.

Long-term di-(2-ethylhexyl) phthalate exposure reduces sorafenib treatment efficacy by enhancing mesenchymal transition in hepatocellular carcinoma.

Di(2-ethylhexyl) phthalate (DEHP) is a worldwide common plasticizer. Nevertheless, DEHP is easily leached out to the environment due to the lack of covalent bonds with plastic. High dose of DEHP exposure is often observed in hemodialysis patients because of the continual usage of plastic medical devices. Although the liver is the major organ that catabolizes DEHP, the impact of long-term DEHP exposure on the sensitivity of liver cancer to chemotherapy remains unclear. In this study, we established long-term DEHP-exposed hepatocellular carcinoma (HCC) cells and two NOD/SCID mice models to investigate the effects and the underlying mechanisms of long-term DEHP exposure on chemosensitivity of HCC. The results showed long-term DEHP exposure potentially increased epithelial-mesenchymal transition (EMT) in HCC cells. Next generation sequencing showed that long-term DEHP exposure increased cell adhesion/migratory related genes expression and blunted sorafenib treatment induced genes alterations. Long-term exposure to DEHP reduced the sensitivity of HCC cells to sorafenib-induced anti-migratory effect by enhancing the EMT transcription factors (slug, twist, and ZEB1) and mesenchymal protein (vimentin) expression. In NOD/SCID mice model, we showed that long-term DEHP-exposed HCC cells exhibited higher growth rate. Regarding the anti-HCC effects of sorafenib, subcutaneous HuH7 tumor grew slowly in sorafenib-treated mice. Nonetheless, the anti-tumor growth effect of sorafenib was not observed in long-term DEHP-exposed mice. Higher mesenchymal markers and proliferating cell nuclear antigen (PCNA) expression were found in sorafenib-treated long-term DEHP-exposed mice. In conclusion, long-term DEHP exposure promoted migratory activity in HCC cells and decreased sorafenib sensitivity in tumor-bearing mice.

Effect of Biofilm Forming on the Migration of Di(2-ethylhexyl)phthalate from PVC Plastics.

Plastic additives, represented by plasticizers, are important components of plastic pollution. Biofilms inevitably form on plastic surfaces when plastic enters the aqueous environment. However, little is known about the effect of biofilms on plastic surfaces on the release of additives therein. In this study, PVC plastics with different levels of di(2-ethylhexyl)phthalate (DEHP) content were investigated to study the effect of biofilm growth on DEHP release. The presence of biofilms promoted the migration of DEHP from PVC plastics to the external environment. Relative to biofilm-free controls, although the presence of surface biofilm resulted in 0.8 to 11.6 times lower DEHP concentrations in water, the concentrations of the degradation product, monoethylhexyl phthalate (MEHP) in water, were 2.3 to 57.3 times higher. When the total release amounts of DEHP in the biofilm and in the water were combined, they were increased by 0.6-73 times after biofilm growth. However, most of the released DEHP was adsorbed in the biofilms and was subsequently degraded. The results of this study suggest that the biofilm as a new interface between plastics and the surrounding environment can affect the transport and transformation of plastic additives in the environment through barrier, adsorption, and degradation. Future research endeavors should aim to explore the transport dynamics and fate of plastic additives under various biofilm compositions as well as evaluate the ecological risks associated with their enrichment by biofilms.

Exposure to di-2-ethylhexyl phthalate (DEHP) increases the risk of cancer.

Cancer is a major socioeconomic burden that seriously affects the life and spirit of patients. However, little is known about the role of environmental toxicant exposure in diseases, especially ubiquitous di-(2-ethylhexyl) phthalate (DEHP) which is one of the most widely used plasticizers. Hence, the objective of this study was to assess the potential association between cancer and DEHP. The data were collected using the 2011-2018 National Health and Nutrition Examination Survey (NHANES) data (n = 6147), and multiple logistic regression was conducted to evaluate the association. The concentrations of DEHP were calculated by each metabolite and split into quartiles for analysis. After adjusting for confounding factors, DEHP was significantly associated with an increased risk of cancer prevalence, and the metabolites of DEHP showed similar results (OR > 1.0, p < 0.05). Simultaneously, the association remained when the analyses were stratified by age and sex, and the risk of cancer appeared to be higher in male patients. In addition, further analysis suggested that DEHP exposure obviously increased the risk of female reproductive system cancer, male reproductive system cancer, and other cancers (OR > 1.0, p < 0.05) but not skin and soft tissue cancer. DEHP exposure is associated with the risk of cancer, especially female reproductive system cancer, male reproductive system cancer and other cancers.

Genistein prevents the production of hypospadias induced by Di-(2-ethylhexyl) phthalate through androgen signaling and antioxidant response in rats.

Environmental estrogen exposure has increased dramatically over the past 50 years. In particular, prenatal exposure to estrogen causes many congenital diseases, among which reproductive system development disorders are extremely serious. In this study, the molecular mechanism of hypospadias and the therapeutic effect of genistein (GEN) were investigated through in vivo models prepared by Di-(2-ethylhexyl) phthalate (DEHP) exposure between 12 and 19 days of gestation. With increased DEHP concentrations, the incidence of hypospadias increased gradually. DEHP inhibited the key enzymes involved in steroid synthesis, resulting in decreasing testosterone synthesis. At the same time, DEHP increased reactive oxygen species (ROS) and produced inflammatory factors via NADPH oxidase-1 (NOX1) and NADPH oxidase-4 (NOX4) pathways. It also inhibited Steroid 5 α Reductase 2 (Srd5α2) and decreased dihydrotestosterone (DHT) synthesis. Additionally, DEHP inhibited the androgen receptor (AR), resulting in reduced DHT binding to the AR that ultimately retarded the development of the external reproductive system. GEN, a phytoestrogen, competes with DEHP for binding to estrogen receptor ß (ERß). This competition, along with GEN's antiestrogen and antioxidant properties, could potentially reverse impairments. The findings of this study provide valuable insights into the role of phytoestrogens in alleviating environmental estrogen-induced congenital diseases.

Associations of urinary di(2-ethylhexyl) phthalate metabolites with lipid profiles among US general adult population.

Background: Di(2-ethylhexyl) phthalate (DEHP) a parent compound that is metabolized into 4 phthalate metabolites, which correlate to adverse cardio-metabolic risk factors. This study aimed to explore the links between urinary DEHP metabolites and serum lipids in the U.S. general adult population. Methods: In this cross-sectional study, data on 11 urinary phthalate metabolites from the 2005-2018 National Health and Nutrition Examination Surveys (NHANES) were analyzed. Multivariate linear regression and restricted cubic spline (RCS) were used to examine the relationship between phthalate metabolites [specific DEHPs: mono-(2-ethyl-5-carboxy-pentyl) phthalate (MECPP), mono-(2-ethyl-5-hydroxy-hexyl) phthalate (MEHHP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-oxo-hexyl) phthalate (MEOHP)] and serum lipids (triglycerides [TG], total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], and high-density lipoprotein cholesterol [HDL-C]). To identify mixed exposure effects of phthalate metabolites, quantile g-computation (QG-C) and weighted quantile sum (WQS) regression were employed for the lipid profiles. Results: A total of 9141 adults were included in the analysis. MECPP, MEHHP, MEHP, and MEOHP in the highest quartile had a negative relationship with HDL-C compared to the lowest quartile (All P for trend <0.05). TG showed a significant positive relation with MECPP, MEHHP, and MEOHP (All P for trend <0.05), but there was no notable association with MEHP. RCS demonstrated a linear relationship of DEHP metabolites with HDL-C, TC, TG, and LDL-C (all P for nonlinearity >0.05). The WQS index of DEHP metabolites showed independent correlations with HDL-C [ß = -0.26, 95%CI (-0.43, -0.09), P = 0.002], TC [ß = 0.55, 95%CI (0.13, 0.98), P = 0.011], and TG [ß = 2.40, 95%CI (0.85, 3.96), P = 0.003]. Conclusion: Our study suggests that environmental DEHP exposure may affect serum HDL-C and TG levels in the general adult population. Further research is warranted to confirm these findings and illuminate the underlying mechanisms of DEHP exposure on lipids.

The mechanism of DEHP degradation by the combined action of biochar and Arthrobacter sp. JQ-1: Mechanisms insight from bacteria viability, degradation efficiency and changes in extracellular environment.

Di(2-ethylhexyl) phthalate (DEHP) has been widely detected in soil, water, and sediment as a priority control pollutant. Immobilized microorganism technology is gradually mature and applied in production. Biochar prepared from agricultural wastes is an excellent immobilized carrier because of its porous structure and abundant functional groups. Environmental acidification was caused by degrading bacteria Arthrobacter sp. JQ-1 (JQ-1) respiration and acidic metabolites during DEHP degradation, which affected the passage life of microorganisms and the removal efficiency of DEHP. The mechanism of DEHP degradation by the combined action of JQ-1 and corn straw biochar (BC) at 600 °C was investigated, and bacterial viability, microenvironmental changes, and kinetic tests were performed in this research. Compared with biodegradation group alone, the degradation rate of DEHP in 1% biochar unloaded and loaded with JQ-1 increased by 18.3% and 30.9%, and its half-life decreased to 23.90 h and 11.95h, a reduction of 31.37 h. The percentage of detected living JQ-1 increased as biochar content increased when loading capacity was less than 1%. In which, (JQ-1-BC2) group was 4.1% higher than (JQ-1-BC1) group. Biochar has the ability to neutralize acidifying environmental pH due to its alkaline functional groups, including lactone group, -OH, -COO-. 1% biochar loaded with JQ-1 increased the pH of the microenvironment by 0.57 and alkaline phosphatase (AKP) activity by 0.0063 U·mL-1, which promoted the reduction of PA. Study suggested that biochar loaded with JQ-1 could simultaneously adsorb and degrade DEHP during the process of DEHP removal. Biochar could be used as a biological stimulant to increase abundance and metabolism, enhance the utilization of DEHP by JQ-1. Biochar (1% (w/v)) loaded with JQ-1 as DEHP removal material showed good performance. Biochar not only as an immobilized carrier, but also as a biostimulant, providing an effective strategy for the collaborative remediation of PAEs contaminated.

Effects of di-(2-ethylhexyl) phthalate on growth, metabolism, and virulence of the plant pathogenic bacterium Acidovorax citrulli.

Acidovorax citrulli is a seed-borne bacterial pathogen that causes bacterial fruit blotch in cucurbits and severely affects the production of cucumbers and watermelons globally. In this study, we investigated the effects of di-(2-ethylhexyl) phthalate (DEHP) on the growth, metabolism, and virulence of A. citrulli. Bacterial population was not affected by DEHP exposure; moreover, significant changes were not observed in lipid peroxidation, membrane permeability, and nucleic acid leakage. However, palmitoleic acid content was increased in the cell membrane of DEHP-exposed A. citrulli. Further, DEHP exposure increased the activity of TCA cycle-related enzymes, including α-ketoglutarate dehydrogenase and succinyl-CoA synthetase, along with increase in the content of glutamate, succinate, fumarate, and malate in TCA cycle. Additionally, total 270 genes were differentially expressed by the treatment, of which 28 genes were upregulated and 242 genes, including those related to translation, flagellum-dependent cell motility, and flagellum assembly, were downregulated. Regarding virulence traits, swimming activity was decreased in DEHP-exposed A. citrulli; however, biofilm formation was not affected in in vitro assay. Moreover, relative expression of pathogenicity genes, including hrpX and hrpG, were decreased in DEHP-exposed A. citrulli compared to that of unexposed A. citrulli. Therefore, these results suggest that DEHP accumulation in soil could potentially influence the metabolism and virulence traits of A. citrulli.

Effects of Di-(2-Ethylhexyl) Phthalate (DEHP) on Gamete Quality Parameters of Male Koi Carp (Cyprinus carpio).

In this study, we evaluated gamete quality parameters of mature male koi carp (Cyprinus carpio) exposed to three different concentrations (1, 10, and 100 µg/L) of di-(2-ethylhexyl) phthalate (DEHP). After 60 days of exposure, there was a significant decrease in the gonadosomatic index (GSI) of males exposed to 10 and 100 µg/L of DEHP. Histological analysis of the testes revealed impaired histoarchitecture, including inflammatory cells, intratubular vacuoles, and swollen seminiferous tubules in treatment groups. Gamete quality parameters like sperm production, motility, spermatocrit, and sperm density values were significantly decreased at the 10 and 100 µg/L concentrations. Biochemical compositions, including glucose, cholesterol, and total protein levels, were significantly changed in the treatment groups. Similarly, the ionic compositions of seminal fluid (Na, K, Ca, and Mg) also varied in the treatment groups. Furthermore, the 11-ketotestosterone levels were decreased, and the 17-ß estradiol levels were increased in the DEHP-treated groups. The mRNA expression levels of reproduction-related genes, including Fshr, Lhr, Ar, Erα, and Erß, were significantly changed in the DEHP-treated males in a dose-dependent manner. In conclusion, the findings of this study confirmed that environmentally relevant exposure to DEHP may contribute to a decline in the gamete quality of male fishes.

The Relationship between Phthalates and Diabetes: A Review.

Since the beginning of their production, in the 1930s, phthalates have been widely used in the plastics industry to provide durability and elasticity to polymers that would otherwise be rigid, or as solvents in hygiene and cosmetic products. Taking into account their wide range of applications, it is easy to understand why their use has been increasing over the years, making them ubiquitous in the environment. This way, all living organisms are easily exposed to these compounds, which have already been classified as endocrine disruptor compounds (EDC), affecting hormone homeostasis. Along with this increase in phthalate-containing products, the incidence of several metabolic diseases has also been rising, namely diabetes. That said, and considering that factors such as obesity and genetics are not enough to explain this substantial increase, it has been proposed that the exposure to environmental contaminants may also be a risk factor for diabetes. Thus, the aim of this work is to review whether there is an association between the exposure to phthalates and the development of the several forms of diabetes mellitus, during pregnancy, childhood, and adulthood.

Long-term exposure to di(2-ethylhexyl) phthalate, diisononyl phthalate, and a mixture of phthalates alters estrous cyclicity and/or impairs gestational index and birth rate in mice.

Phthalates are found in plastic food containers, medical plastics, and personal care products. However, the effects of long-term phthalate exposure on female reproduction are unknown. Thus, this study investigated the effects of long-term, dietary phthalate exposure on estrous cyclicity and fertility in female mice. Adult female CD-1 mice were fed chow containing vehicle control (corn oil) or 0.15-1500 ppm of di(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DiNP), or a mixture of phthalates (Mix) containing DEHP, DiNP, benzyl butyl phthalate, di-n-butyl phthalate, diisobutyl phthalate, and diethyl phthalate. Measurements of urinary phthalate metabolites confirmed effective delivery of phthalates. Phthalate consumption for 11 months did not affect body weight compared to control. DEHP exposure at 0.15 ppm for 3 and 5 months increased the time that the mice spent in estrus and decreased the time the mice spent in metestrus/diestrus compared to control. DiNP exposure (0.15-1500 ppm) did not significantly affect time in estrus or metestrus/diestrus compared to control. Mix exposure at 0.15 and 1500 ppm for 3 months decreased the time the mice spent in metestrus/diestrus and increased the time the mice spent in estrus compared to control. DEHP (0.15-1500 ppm) or Mix (0.15-1500 ppm) exposure did not affect fertility-related indices compared to control. However, long-term DiNP exposure at 1500 ppm significantly reduced gestational index and birth rate compared to control. These data indicate that chronic dietary exposure to phthalates alters estrous cyclicity, and long-term exposure to DiNP reduces gestational index and birth rate in mice.

Di-(2-ethylhexyl) phthalate (DEHP) promoted hepatic lipid accumulation by activating Notch signaling pathway.

Di-(2-ethylhexyl) phthalate (DEHP) and mono-2-ethylhexyl phthalate (MEHP) can induce hepatic lipid metabolism disorders, while the molecular mechanism still remain unknown. We aim to explore the underlying mechanism of Notch signaling pathway on hepatic lipid accumulation induced by DEHP/MEHP. A total of 40 male wistar rats were exposed to DEHP (0, 5, 50, and 500 mg/kg/d) for 8 weeks, BRL-3A hepatocytes were exposed to MEHP (0, 10, 50, 100, and 200 µM) for 24 h. About 50 µM DAPT and 100 µg/mL Aspirin were used to inhibit Notch pathway and prevent inflammation, respectively. Real-Time PCR was performed to detect the mRNA expression, western blot and immunofluorescence were used to detect the protein expression. Lipids and inflammatory factors levels were determined by commercial kits. The results showed that DEHP/MEHP promoted the expression of Notch pathway molecules and lipids accumulation in rat livers/BRL-3A cells. The up-regulated Notch receptors were correlated with the TG levels in the rat liver. MEHP increased the levels of IL-8 and IL-1ß. The lipids levels were reduced after anti-inflammation. The inhibition of Notch pathway reversed the elevation of inflammation and lipid accumulation caused by MEHP. In conclusion, this study demonstrated that DEHP/MEHP led to lipid accumulation in hepatocytes by up-regulating Notch pathway and the inflammation might play a key role in the process.

Evaluation of soil ecological health after exposure to environmentally relevant doses of Di (2-ethylhexyl) phthalate: Insights from toxicological studies of earthworms at different ecological niches.

As one of the most critical soil faunas in agroecosystems, earthworms are significant in preserving soil ecological health. Di (2-ethylhexyl) phthalate (DEHP) is a major plasticizer and widely used in plastic products like agricultural films. However, it has become ubiquitous contaminant in agricultural soil and poses a potential threat to soil health. Although the awareness of the impacts of DEHP on soil ecology is increasing, its adverse effects on soil invertebrates, especially earthworms, are still not well developed. In this study, the ecotoxicological effects and underlying mechanisms of environmentally relevant doses DEHP on earthworms of different ecological niches were investigated at the individual, cytological, and biochemical levels, respectively. Results showed that the acute toxicity of DEHP to M. guillelmi was higher than E. foetida. DEHP induced reactive oxygen species (ROS) levels and further caused oxidative damage (including cellular DNA and lipid peroxidation damage) in both species, speculating that they may exhibit similar oxidative stress mechanisms. Furthermore, two earthworms presented the alleviated toxicity when re-cultured in uncontaminated circumstances, yet, the accumulated ROS in bodies could not be completely scavenged. Risk assessment indicated that the detrimental impacts of DEHP were more significant in the M. guillelmi than in E. foetida in whole experiments prides, and the biomarkers additionally showed a species-specific trend. Besides, molecular docking revealed that DEHP could bind to the active center of superoxide dismutase/catalase (SOD/CAT) by hydrogen bonding or hydrophobic interactions. Overall, this study will provide a novel insight for accurate contaminant risk assessment, and also highlight that the comprehensive biological effects of different species should be emphasized in soil ecological health diagnostics and environmental toxicology assays, as otherwise it may lead to underestimation or misestimation of the soil health risk of contaminants.

Impact of Plasticizer on the Intestinal Epithelial Integrity and Tissue-Repairing Ability within Cells in the Proximity of the Human Gut Microbiome.

Toxicological research into the impact of plasticizer on different organs has been reported in the past few decades, while their effects on shifting the gut microbiota and immune cells homeostasis in zebrafish were only studied recently. However, studies on the impact of plasticizer on human gut microbiota are scarce. In this study, we co-incubated healthy human fecal microbiota with different concentrations of Di(2-ethylhexyl) phthalate (DEHP) and di-iso-nonyl phthalate (DINP), analyzed microbial composition by 16S rDNA sequencing, and compared the influence of their derived microbiomes on the human enterocyte (HT-29) and murine macrophage (RAW264.7) cell lines. Microbial diversity is reduced by DEHP treatment in a dose-dependent manner. DEHP treatment reduced the phyla Firmicutes/Bacteroidetes ratio, while DINP treatment promoted Proteobacteria. Expressions of tight/adherens junction genes in HT-29 and anti-inflammatory genes in RAW264.7 were down-regulated by plasticizer-co-incubated microbiota derived metabolites. Overall, it is observed that selected plasticizers at high dosages can induce compositional changes in human microbiota. Metabolites from such altered microbiota could affect the tight junction integrity of the intestinal epithelium and upset macrophage differentiation homeostasis in proximity. Chronic exposure to these plasticizers may promote risks of dysbiosis, leaky gut or the exacerbation of intestinal inflammation.

Hydrolysis of dibutyl phthalate and di(2-ethylhexyl) phthalate in human liver, small intestine, kidney, and lung: An in vitro analysis using organ subcellular fractions and recombinant carboxylesterases.

Phthalates are widely used plasticizers that are primarily and rapidly metabolized to monoester phthalates in mammals. In the present study, the hydrolysis of dibutyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP) in the human liver, small intestine, kidney, and lung was examined by the catalytic, kinetic, and inhibition analyses using organ microsomal and cytosolic fractions and recombinant carboxylesterases (CESs). The Vmax (y-intercept) values based on the Eadie-Hofstee plots of DBP hydrolysis were liver > small intestine > kidney > lung in microsomes, and liver > small intestine > lung > kidney in cytosol, respectively. The CLint values (x-intercept) were small intestine > liver > kidney > lung in both microsomes and cytosol. The Vmax and CLint or CLmax values of DEHP hydrolysis were small intestine > liver > kidney > lung in both microsomes and cytosol. Bis(4-nitrophenyl) phosphate (BNPP) effectively inhibited the activities of DBP and DEHP hydrolysis in the microsomes and cytosol of liver, small intestine, kidney, and lung. Although physostigmine also potently inhibited DBP and DEHP hydrolysis activities in both the microsomes and cytosol of the small intestine and kidney, the inhibitory effects in the liver and lung were weak. In recombinant CESs, the Vmax values of DBP hydrolysis were CES1 (CES1b, CES1c) > CES2, whereas the CLmax values were CES2 > CES1 (CES1b, CES1c). On the other hand, the Vmax and CLmax values of DEHP hydrolysis were CES2 > CES1 (CES1b, CES1c). These results suggest an extensive organ-dependence of DBP and DEHP hydrolysis due to CES expression, and that CESs are responsible for the metabolic activation of phthalates.

Phthalates cause a low-renin phenotype commonly found in premature infants with idiopathic neonatal hypertension.

Since the 1970s, when the initial reports of neonatal hypertension related to renal artery thromboembolism were published, other secondary causes of neonatal hypertension have been reported. Those infants with no identifiable cause of hypertension were labeled with a variety of terms. Herein, we describe such infants as having idiopathic neonatal hypertension (INH). Most, but not all, of these hypertensive infants were noted to have bronchopulmonary dysplasia (BPD). More recently, reports described common clinical characteristics seen in INH patients, whether or not they had BPD. This phenotype includes low plasma renin activity, presentation near 40 weeks postmenstrual age, and a favorable response to treatment with spironolactone. A small prospective study in INH patents showed evidence of mineralocorticoid receptor activation due to inhibition of 11ß-HSD2, the enzyme that converts cortisol to the less potent mineralocorticoid-cortisone. Meanwhile, phthalate metabolites have been shown to inhibit 11ß-HSD2 in human microsomes. Premature infants can come in contact with exceptionally large phthalate exposures, especially those infants with BPD. This work describes a common low-renin phenotype, commonly seen in patients categorized as having INH. Further, we review the evidence that hypertension in INH patients with the low-renin phenotype may be mediated by phthalate-associated inhibition of 11ß-HSD2. Lastly, we review the implications of these findings regarding identification, treatment, and prevention of the low-renin hypertension phenotype seen in premature infants categorized as having INH.