Phthalate esters(PAEs)are widely used as main plasticizers in plastic products,agricultural regulators,toys,and other fields.This paper reviewed the research progress on the distribution,sources,and ecological effects...Phthalate esters(PAEs)are widely used as main plasticizers in plastic products,agricultural regulators,toys,and other fields.This paper reviewed the research progress on the distribution,sources,and ecological effects of PAEs.The effects of PAEs on soil microorganisms,animals,plants and soil properties were explored in sequence,providing effective theoretical basis for future research on PAEs.展开更多
Objective This study investigated the effects of bis(2-butoxyethyl) phthalate(BBOP) on the onset of male puberty by affecting Leydig cell development in rats.Methods Thirty 35-day-old male Sprague-Dawley rats were ran...Objective This study investigated the effects of bis(2-butoxyethyl) phthalate(BBOP) on the onset of male puberty by affecting Leydig cell development in rats.Methods Thirty 35-day-old male Sprague-Dawley rats were randomly allocated to five groups mg/kg bw per day that were gavaged for 21 days with BBOP at 0, 10, 100, 250, or 500 mg/kg bw per day. The hormone profiles;Leydig cell morphological metrics;mRNA and protein levels;oxidative stress;and AKT,mTOR, ERK1/2, and GSK3β pathways were assessed.Results BBOP at 250 and/or 500 mg/kg bw per day decreased serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels mg/kg bw per day(P < 0.05). BBOP at 500 mg/kg bw per day decreased Leydig cell number mg/kg bw per day and downregulated Cyp11a1, Insl3, Hsd11b1,and Dhh in the testes, and Lhb and Fshb mRNAs in the pituitary gland(P < 0.05). The malondialdehyde content in the testis significantly increased, while Sod1 and Sod2 mRNAs were markedly downregulated, by BBOP treatment at 250–500 mg/kg bw per day(P < 0.05). Furthermore, BBOP at 500mg/kg bw per day decreased AKT1/AKT2, mTOR, and ERK1/2 phosphorylation, and GSK3β and SIRT1levels mg/kg bw per day(P < 0.05). Finally, BBOP at 100 or 500 μmol/L induced ROS and apoptosis in Leydig cells after 24 h of treatment in vitro(P < 0.05).Conclusion BBOP delays puberty onset by increasing oxidative stress and apoptosis in Leydig cells in rats.The graphical abstract is available on the website www.besjournal.com.展开更多
BACKGROUND Di(2-ethylhexyl)phthalate(DEHP)is a common plasticizer known to cause liver injury.Green tea is reported to exert therapeutic effects on heavy metal exposureinduced organ damage.However,limited studies have...BACKGROUND Di(2-ethylhexyl)phthalate(DEHP)is a common plasticizer known to cause liver injury.Green tea is reported to exert therapeutic effects on heavy metal exposureinduced organ damage.However,limited studies have examined the therapeutic effects of green tea polyphenols(GTPs)on DEHP-induced liver damage.AIM To evaluate the molecular mechanism underlying the therapeutic effects of GTPs on DEHP-induced liver damage.METHODS C57BL/6J mice were divided into the following five groups:Control,model[DEHP(1500 mg/kg bodyweight)],treatment[DEHP(1500 mg/kg bodyweight)+GTP(70 mg/kg bodyweight),oil,and GTP(70 mg/kg bodyweight)]groups.After 8 wk,the liver function,blood lipid profile,and liver histopathology were examined.Differentially expressed micro RNAs(miRNAs)and mRNAs in the liver tissues were examined using high-throughput sequencing.Additionally,functional enrichment analysis and immune infiltration prediction were performed.The miRNA-mRNA regulatory axis was elucidated using the starBase database.Protein expression was evaluated using immunohistochemistry.RESULTS GTPs alleviated DHEP-induced liver dysfunction,blood lipid dysregulation,fatty liver disease,liver fibrosis,and mitochondrial and endoplasmic reticulum lesions in mice.The infiltration of macrophages,mast cells,and natural killer cells varied between the model and treatment groups.mmu-miR-141-3p(a differentially expressed miRNA),Zcchc24(a differentially expressed mRNA),and Zcchc24(a differentially expressed protein)constituted the miRNA-mRNA-protein regulatory axis involved in mediating the therapeutic effects of GTPs on DEHP-induced liver damage in mice.CONCLUSION This study demonstrated that GTPs mitigate DEHP-induced liver dysfunction,blood lipid dysregulation,fatty liver disease,and partial liver fibrosis,and regulate immune cell infiltration.Additionally,an important miRNAmRNA-protein molecular regulatory axis involved in mediating the therapeutic effects of GTPs on DEHP-induced liver damage was elucidated.展开更多
Pharmaceutical companies that produce gastrointestinal(GI)medications often utilize phthalates for their ability to localize medication release.Commonly prescribed GI medications that may utilize phthalates are 5-Amin...Pharmaceutical companies that produce gastrointestinal(GI)medications often utilize phthalates for their ability to localize medication release.Commonly prescribed GI medications that may utilize phthalates are 5-Aminosalicylates,proton pump inhibitors,and pancreatic enzymes.Our understanding of the cumulative health effects of phthalates from medications remains unclear,and there is increasing evidence that phthalates are not harmless.Experimental studies in animals have shown that phthalates,specifically dibutyl phthalate and Di-(2-ethyl-hexyl)phthalate,have the potential to alter and/or inhibit reproductive biology and in utero development.Despite the lack of definitive human data,many cohort and cross-sectional studies demonstrate concerning associations between phthalates and poor health status,specifically developmental problems.Longitudinal studies and studies with larger sample sizes are required to determine whether phthalates actually cause negative health consequences.It is also important that physicians regularly review and discuss with patients the medicinal ingredients in their medications and supplements,specifically in pregnant woman with inflammatory bowel disease.展开更多
Phthalates have been used in a wide variety of consumer goods. Their versatility as plasticizers has translated into worldwide use in a vast array of consumer products. These compounds can leach into matrices, such as...Phthalates have been used in a wide variety of consumer goods. Their versatility as plasticizers has translated into worldwide use in a vast array of consumer products. These compounds can leach into matrices, such as food and liquids that can be routed for human exposure. One of the most used phthalates is Diethylhexyl phthalate (DEHP). Diethylhexyl phthalate and its metabolite 2-ethyl-1-hexanol (2-EH) have demonstrated biological effects which merit further evaluation. In this work, we expand on our previous work with DEHP and screen the 2-EH metabolite for different cell death endpoints such as growth inhibition, apoptosis, autophagy, caspase activation, DNA fragmentation, and cell cycle arrest using fluorophores and the NC3000 instrument. Significant results (p 0.05) revealed higher toxicity for the 2-EH metabolite when compared to DEHP. Also, 2-EH presented apoptosis induction with characteristic hallmarks, such as loss of mitochondrial membrane potential, caspase activation, DNA fragmentation and cell cycle arrest at the S phase. In addition, the presence of autophagosome was detected through L3CB protein staining. We conclude that 2-EH presents differences in cell death endpoints that interestingly differ from the DEHP parent compound. Further studies are needed to establish the molecular pathways responsible for the observed effects.展开更多
Human beings are increasingly exposed to phthalates,which are a group of chemicals used to make plastics more flexible and harder to break,and simultaneously ingesting abundant food emulsifiers via daily diet.The purp...Human beings are increasingly exposed to phthalates,which are a group of chemicals used to make plastics more flexible and harder to break,and simultaneously ingesting abundant food emulsifiers via daily diet.The purpose of this study was to investigate the effect of the food emulsifier glycerin monostearate(GMS)on male reproductive toxicity caused by di(2-ethylhexyl)phthalate(DEHP,one of the phthalates)and explore the underlying mechanism.Thirty male Sprague-Dawley rats were randomly divided into control group,DEHP group and DEHP+GMS group.Rats in the DEHP group and DEHP+GMS group were orally administered with 200 mg/kg/d DEHP with or without 20 mg/kg/d GMS.After 30 days of continuous intervention,it was found that the serum testosterone level was significantly lowered in DEHP group and DEHP+GMS group than that in control group(P<0.01).The serum testosterone level and the relative testis weight were significantly decreased in the DEHP+GMS group as compared with those in the DEHP group and control group(P<0.05).More spermatids were observed to be shed off in DEHP+GMS group than in DEHP group.The expression levels of cell cycle checkpoint kinase 1(Chkl),cell division cycle gene 2(Cdc2),and cyclin-dependent kinase 2(CDK2)were down-regulated in DEHP group,and this tendency was more significant in DEHP+GMS group(P<0.05 or P<0.01).There was no significant difference in the P-glycoprotein(P-gp)expression between DEHP group and control group.However,P-gp was markedly down-regulated in DEHP+GMS group(P<O.Ol).The results indicated that the food emulsifier GMS aggravated the toxicity of DEHP on male reproduction by inhibiting the cell cycle of testicular cells and the expression of P-gp in testis tissues.展开更多
Hexafluoroisopropanol(HFIP)-induced sodium dodecyl sulfate/dodecyltrimethylammonium bromide(SDS/DTAB) catanionic surfactant coacervate extraction method coupled with high performance liquid chromatography(HPLC) was us...Hexafluoroisopropanol(HFIP)-induced sodium dodecyl sulfate/dodecyltrimethylammonium bromide(SDS/DTAB) catanionic surfactant coacervate extraction method coupled with high performance liquid chromatography(HPLC) was used to detect the migration of phthalates from disposable tablewares to drinking water. The concentration factors are larger than 82 and extraction recoveries over 53% for water samples spiked with 100 or 200 ng/m L phthalates. Limit of detection is in the range of 1.0–2.6 ng/m L.Good linearity with correlation coefficients larger than 0.9985 is obtained in the concentration of20–1500 or 40–3000 ng/m L. Relative recoveries are from 82.4% to 123.6% for water samples spiked with30/60, 250/500, and 1500/3000 ng/m L phthalates, respectively. Relative standard deviations(RSDs) are0.4%–7.4% for intraday precision(n = 5) and 0.6%–7.8% for interday precision(n = 3). Four of studied phthalates are found in the drinking water samples prepared from four kinds of tablewares.展开更多
This paper describes the electrodeposition of polyphosphate-doped polypyrrole/nanosilica nano-composite coating on steel wire for direct solid-phase microextraction of bisphenol A and five phthalates. We optimized inf...This paper describes the electrodeposition of polyphosphate-doped polypyrrole/nanosilica nano-composite coating on steel wire for direct solid-phase microextraction of bisphenol A and five phthalates. We optimized influencing parameters on the extraction efficiency and morphology of the nanocomposite such as deposition potential, concentration of pyrrole and polyphosphate, deposition time and the nanosilica amount. Under the optimized conditions, characterization of the nanocomposite was inves-tigated by scanning electron microscopy and Fourier transform infra-red spectroscopy. Also, the factors related to the solid-phase microextraction method including desorption temperature and time, extrac-tion temperature and time, ionic strength and pH were studied in detail. Subsequently, the proposed method was validated by gas chromatography-mass spectrometry by thermal desorption and acceptable figures of merit were obtained. The linearity of the calibration curves was between 0.01 and 50 ng/mL with acceptable correlation coefficients (0.9956-0.9987) and limits of detection were in the range 0.002-0.01 ng/mL. Relative standard deviations in terms of intra-day and inter-day by five replicate analyses from aqueous solutions containing 0.1 ng/mL of target analytes were in the range 3.3%-5.4% and 5%-7.1%, respectively. Fiber-to-fiber reproducibilities were measured for three different fibers prepared in the same conditions and the results were between 7.3% and 9.8%. Also, extraction recoveries at two different concentrations were ≥96%. Finally, the suitability of the proposed method was demonstrated through its application to the analysis of some eye drops and injection solutions.展开更多
Objective Prenatal phthalate exposure has been associated with placental inflammatory factors and infant allergic rhinitis(AR).However,the results are inconclusive.We designed a population-based cohort study to examin...Objective Prenatal phthalate exposure has been associated with placental inflammatory factors and infant allergic rhinitis(AR).However,the results are inconclusive.We designed a population-based cohort study to examine the effects of placental inflammatory biomarkers on the sex-dependent associations between maternal phthalate exposure and infant AR.Methods A total of 2,348 pregnant women from Ma’anshan,Anhui Province,China,who were screened before antenatal visits and met the inclusion criteria,were included in the present study.We assessed AR in their offspring aged 36 months with a questionnaire.Quantitative PCR was performed to measure placental inflammatory factor m RNAs.The independent samples t-test and multivariable logistic regression were used to determine the associations between infant AR and maternal phthalates.Results Childhood AR may be related to education and family monthly income(P = 0.01).The phthalate metabolites,mono(2-ethylhexyl) phthalate(MEHP),mono(2-ethyl-5-hydroxyl) phthalate(MEHHP),in pregnant women were associated with a significantly increased risk for infant AR in males[P < 0.05;odds ratio(OR):1.285;95% confidence interval(CI):1.037-1.591,and OR:1.232,95% CI:1.008-1.507,respectively],but not females.Additionally,irritably-increased expression levels of HO-1 and IL-4 were associated with AR in male infants(OR:1.175;95% CI:1.038-1.329 and OR:1.181;95% CI:1.056-1.322,respectively).The association between maternal urinary MEHHP and placental HO-1 was marginally significant according to mediation analysis.Conclusion The associations of maternal MEHHP and MEOHP levels with fetal AR in males were significant.Placental HO-1 was a fractional mediator in the associations between MEHHP and AR.Thus,the placenta should be further investigated as a potential mediator of maternal exposure-induced disease risk in children.展开更多
The objective of this study was to determine the concentrations of the metabolites of four selected phthalates, widely used industrial chemicals which possess endocrine-disrupting properties, in samples of amniotic fl...The objective of this study was to determine the concentrations of the metabolites of four selected phthalates, widely used industrial chemicals which possess endocrine-disrupting properties, in samples of amniotic fluid and maternal urine collected in the same day, in order to verify if the latter can be considered a measure of the fetal exposure. The quantitative determination of the metabolites was carried out by HPLC-MS/MS with isotopic dilution from 70 pregnant volunteers. Detectable concentrations of phthalates metabolites were found in amniotic fluids. As phthalate monoesters are excreted in the urine conjugated with glucuronic acid, an enzymatic hydrolysis is carried out before analysis. Amniotic fluids were tested with and without hydrolysis and only the free phthalate metabolites, not conjugated with glucuronic acid, were found. The concentration of metabolites after enzymatic hydrolysis in maternal urine is not correlated to those of amniotic fluids, but the free form concentrations are. These results suggest that only the free forms can cross the placenta. A significant number of mothers showed urine phthalate monoesters concentrations higher than non-pregnant women.展开更多
This study investigated the occurrence and distribution of 15 phthalate esters(PAEs) in sediments collected from Qixinghe wetlands, northeast China. Total concentration of PAEs in all sediments ranged from 128.41 to 5...This study investigated the occurrence and distribution of 15 phthalate esters(PAEs) in sediments collected from Qixinghe wetlands, northeast China. Total concentration of PAEs in all sediments ranged from 128.41 to 502.79 μg kg^(-1), with the mean value of 284.61 μg kg^(-1).PAEs significantly differed among wetland types; the average PAEs concentration of surface sediments were as follows: Phragmites australis wetland(PAW, 419.87 ±73.61 μg kg^(-1)) [ Carex lasiocarpa wetland(CLW,304.18 ± 56.47 μg kg^(-1)) [ Deyeuxia angustifolia wetland(DAW, 129.78 ± 18.24 μg kg^(-1)). Dimethyl phthalate(DMP), diisobutyl phthalate, di-n-butyl phthalate, and di-(2-ethylhexyl) phthalate(DEHP) were found in all sediments,DEHP was the most abundant PAEs congeners with concentrations varying from 37.62 to 294.9 μg kg^(-1). DMP and DEHP exhibited relatively higher concentrations in CLW and PAW wetlands than in DAW, indicating that the different deoxidization and biodegradation conditions could have important implications for the distribution patterns of PAEs in wetland sediments. The variation of PAEs concentrations in horizontal and vertical sediments with wetland types could be attributed to the migration of contaminants by surface water, groundwater and atmospheric deposition. The occurrence and distribution of PAEs in wetlands also sμggests that contamination in natural ecosystems should not be overlooked.展开更多
The biodegradation of dimethyl phthalate(DMP)was investigated under fermentative conditions in this study.The nature of the intermediate compounds and the extent of mineralization were probed using high-pressure liqui...The biodegradation of dimethyl phthalate(DMP)was investigated under fermentative conditions in this study.The nature of the intermediate compounds and the extent of mineralization were probed using high-pressure liquid chromatography(HPLC)and liquid chromatography-mass spectrometry(LC-MS)methods.The fermentative bacteria were able to biodegrade the DMP under anaerobic conditions,with the biodegradation rate of 0.36 mg DMP/(L·h).The results demonstrated that the DMP degradation under fermentative conditio...展开更多
Objective Di-(2-ethylhexyl) phthalate(DEHP) is a ubiquitous environmental contaminant.As an endocrine disruptor,it seriously threatens human health and ecological environmental safety.This study examines the impact of...Objective Di-(2-ethylhexyl) phthalate(DEHP) is a ubiquitous environmental contaminant.As an endocrine disruptor,it seriously threatens human health and ecological environmental safety.This study examines the impact of intervention with soybean isoflavones(SIF) on DEHP-induced toxicity using a metabonomics approach.Methods Rats were randomly divided into control(H),SIF-treated(A,86 mg/kg body weight),DEHP-treated(B,68 mg/kg),and SIF plus DEHP-treated(D) groups.Rats were given SIF and DEHP daily through diet and gavage,respectively.After 30 d of treatment,rat urine was tested using UPLC/MS with multivariate analysis.Metabolic changes were also evaluated using biochemical assays.Results Metabolomics analyses revealed that p-cresol glucuronide,methyl hippuric acid,N1-methyl-2-pyridone-5-carboxamide,lysophosphatidycholine [18:2(9 Z,12 Z)] {lyso PC [18:2(9 Z,12 Z)]},lyso PC(16:0),xanthosine,undecanedioic acid,and N6-acetyl-l-lysine were present at significantly different levels in control and treatment groups.Conclusion SIF supplementation partially protects rats from DEHP-induced metabolic abnormalities by regulating fatty acid metabolism,antioxidant defense system,amino acid metabolism,and is also involved in the protection of mitochondria.展开更多
Ovary plays an important role in the female reproductive system.The maintenance and regulation of ovarian function are affected by various physical and chemical factors.With the development of industrialization,enviro...Ovary plays an important role in the female reproductive system.The maintenance and regulation of ovarian function are affected by various physical and chemical factors.With the development of industrialization,environmental pollutants have caused great harm to public health.Phthalates,as a class of endocrine-disrupting chemicals(EDCs),are synthesized and used in large quantities as plasticizers due to their chemical properties.They are easily released into environment because of their noncovalent interactions with substances,causing human exposure and possibly impairing ovary.In recent years,more and more attention has been paid to the role of epigenetics in the occurrence and development of diseases.And it is urgent to study the role of methylation,gene imprinting,miRNA,and other epigenetic mechanisms in reproductive toxicology.展开更多
This study represents, detailly, the validated method for the extraction and quantification of widespread phthalic acid esters (PAEs) bis(2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DBP) and di-n-octyl phtha...This study represents, detailly, the validated method for the extraction and quantification of widespread phthalic acid esters (PAEs) bis(2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DBP) and di-n-octyl phthalate (DnOP) from solitary ascidians collected from a marine environment. The extraction was based on a pressurized liquid extraction method, using n-hexane as the solvent to extract the target PAEs from dry biological tissues, and was performed in an accelerated solvent extraction instrument. The average recovery of 89.2% was obtained from samples subjected to a pressure of ~1500 psi and 120°C in two 10-min cycles. GC-MS was used for quantification, conducted in single-ion monitoring mode. Following careful and rigorous cleanup procedures to prevent cross-contamination from laboratory glassware, PAE standards showed signals with good specificity. The obtained limits of detection were 130, 122 and 89 ng/g for DEHP, DBP and DnOP, respectively. Accordingly, the calculated limits of quantification were 394, 370 and 270 ng/g for DEHP, DBP and DnOP, respectively. The obtained linearity ranged from 5.4 to 269 ng/ml (equivalent to 135 - 6725 ng/g dry weight), with R2 ≥ 0.998. Concentrations in the range of 200 to 9000 and 400 to 5000 ng/g sample dry weight, for DEHP and DBP, respectively, were obtained from the ascidians. No DnOP was detected in any of the samples. These results indicate that the method presented in this study is applicable for detection of low and trace concentrations of the target PAEs in samples collected from a marine organism, which can serve as a bioindicator of plastic contamination.展开更多
Medical wastes have been implicated in river pollution in developing countries and most often people depend on water from such rivers for sources of livelihood. Phthalates (endocrine disruptors) are major components i...Medical wastes have been implicated in river pollution in developing countries and most often people depend on water from such rivers for sources of livelihood. Phthalates (endocrine disruptors) are major components in medical wastes and are commonly found contaminants in aquatic environment. Most sewage treatment facilities handling medical waste are inefficient due to overuse and poor maintenance and discharge directly into rivers. This study aimed to investigate the identity and estimates the concentration of phthalates in supposed treated medical wastes from a hospital sewer and water from a receiving river. Samples were randomly collected before and after treatment by the sewer plants, while samples were randomly collected along the course of the river starting from point of discharge. Control samples were taken from upstream about 500 m along the river course. The samples were extracted by liquid-liquid chroma- tographic process using dichloromethane, after which they were cleaned up in a column of silica gel using hexane as the mobile solvent. The cleaned extracts were analyzed by HPLC. The concentrations (μg/L) of dimethyl-, diethyl-, diphenyl-, dibutyl- and di-(2-ethyl)hexyl phthalates ranged from 62.81 ± 18.53;4.74 ± 3.57;2.05 ± 1.80;11.40 ± 5.58 to 141.92 ± 35.8 respectively in the sewer waste. The receiving river had a concentration (μg/L) of 9.17 ± 14.02;0.18 ± 0.31;0.48 ± 0.84;2.84 ± 1.21;61.72 ± 38.35 respectively for dimethyl-, diethyl-, diphenyl-, dibutyl- and di-(2-ethyl) hexyl phthalates. These concentrations were higher than control and far exceeded the USEPA limits of 3 μg/l recom- mended for phthalates in water. Contaminants of aquatic environment by untreated wastes from hospitals has serious implications on public health and environment as human risks for phthalate esters downstream are high and this calls for urgent need to develop strategy to build incentives for compliance in treatment and discharge of wastes into river waters.展开更多
Immunity is crucial to the health of animals and it can determine their survival and fitness. Di(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer and hence is the most abundant phthalate in the environme...Immunity is crucial to the health of animals and it can determine their survival and fitness. Di(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer and hence is the most abundant phthalate in the environment. Exposure to DEHP is of great concern for human health. In the present study, we tested the hypothesis that exposure to DEHP would suppress T cell-mediated immunity in mice. Twenty adult male Kunming mice were randomly assigned into the control (n = 10) and the DEHP treatment (n = 10) groups. Both groups have free access to food and water, while the mice in the latter group drank DEHP solution (2000 mg/L) for 42 days. T cell-mediated immunity assessed by phytohaemagglutinin (PHA) response was depressed in the DEHP treated mice compared with the controls, however, wet thymus and spleen mass, white blood cells were not influenced by DEHP treatment. Taken together, different immunological parameters responded differently to DEHP treatment in Kunming mice.展开更多
Our previous studies revealed the polycyclic aromatic hydrocarbon and phthalic acid esters were the major organic pollutants in the Jialing River and Yangtze River in the Three Gorges area, and they might cause the to...Our previous studies revealed the polycyclic aromatic hydrocarbon and phthalic acid esters were the major organic pollutants in the Jialing River and Yangtze River in the Three Gorges area, and they might cause the toxicity in male fertility when combined. Thus we used di-n-butyl phthalate (DBP) and Benzo(a)pyrene (Bap) as their representatives respectively to explore their effects on the spermatogenesis in male rats. Male Sprague Dawley rats were randomly divided into 4 groups and respectively exposed to corn oil, Bap (5 mg/kg/d), DBP (250 mg/kg/d), and combined doses of Bap (5 mg/kg/d) and DBP (250 mg/kg/d) for 90 days. We observed a significant increase in the stillbirth rate after Bap and combined treatments, while the mean area of seminiferous tubules was reduced after Bap, DBP and combined treatments. Bap and combined treatment had a sup- pressing effect on meiosis in germ cells, which reduced the haploid contents and the ratio between haploid and diploid but increased the tetraploid and diploid contents and the ratio between hap- loid and tetraploid. These effects were more obvious in the combined group. Furthermore, the ex- pression of a number of proteins was changed, of which was associated with the oxidative stress and cAMP/PKA signaling pathway. Our results suggest that Bap has significant toxic effects on male fertility, while the combined treatment of Bap and DBP has more toxic effects.展开更多
基金Supported by Undergraduate Innovation and Entrepreneurship Training Program (202310580018).
文摘Phthalate esters(PAEs)are widely used as main plasticizers in plastic products,agricultural regulators,toys,and other fields.This paper reviewed the research progress on the distribution,sources,and ecological effects of PAEs.The effects of PAEs on soil microorganisms,animals,plants and soil properties were explored in sequence,providing effective theoretical basis for future research on PAEs.
基金supported by the National Natural Science Fund of China[no.81730042]。
文摘Objective This study investigated the effects of bis(2-butoxyethyl) phthalate(BBOP) on the onset of male puberty by affecting Leydig cell development in rats.Methods Thirty 35-day-old male Sprague-Dawley rats were randomly allocated to five groups mg/kg bw per day that were gavaged for 21 days with BBOP at 0, 10, 100, 250, or 500 mg/kg bw per day. The hormone profiles;Leydig cell morphological metrics;mRNA and protein levels;oxidative stress;and AKT,mTOR, ERK1/2, and GSK3β pathways were assessed.Results BBOP at 250 and/or 500 mg/kg bw per day decreased serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels mg/kg bw per day(P < 0.05). BBOP at 500 mg/kg bw per day decreased Leydig cell number mg/kg bw per day and downregulated Cyp11a1, Insl3, Hsd11b1,and Dhh in the testes, and Lhb and Fshb mRNAs in the pituitary gland(P < 0.05). The malondialdehyde content in the testis significantly increased, while Sod1 and Sod2 mRNAs were markedly downregulated, by BBOP treatment at 250–500 mg/kg bw per day(P < 0.05). Furthermore, BBOP at 500mg/kg bw per day decreased AKT1/AKT2, mTOR, and ERK1/2 phosphorylation, and GSK3β and SIRT1levels mg/kg bw per day(P < 0.05). Finally, BBOP at 100 or 500 μmol/L induced ROS and apoptosis in Leydig cells after 24 h of treatment in vitro(P < 0.05).Conclusion BBOP delays puberty onset by increasing oxidative stress and apoptosis in Leydig cells in rats.The graphical abstract is available on the website www.besjournal.com.
基金Guangdong Provincial Department of Science and Technology,Science and Technology Plan Project,Journal of Jinan University High-Level Science and Technology Journal Construction Project,No.2021B121020012Guangdong Provincial Administration of Traditional Chinese Medicine,Traditional Chinese Medicine Research Project,No.20213005.
文摘BACKGROUND Di(2-ethylhexyl)phthalate(DEHP)is a common plasticizer known to cause liver injury.Green tea is reported to exert therapeutic effects on heavy metal exposureinduced organ damage.However,limited studies have examined the therapeutic effects of green tea polyphenols(GTPs)on DEHP-induced liver damage.AIM To evaluate the molecular mechanism underlying the therapeutic effects of GTPs on DEHP-induced liver damage.METHODS C57BL/6J mice were divided into the following five groups:Control,model[DEHP(1500 mg/kg bodyweight)],treatment[DEHP(1500 mg/kg bodyweight)+GTP(70 mg/kg bodyweight),oil,and GTP(70 mg/kg bodyweight)]groups.After 8 wk,the liver function,blood lipid profile,and liver histopathology were examined.Differentially expressed micro RNAs(miRNAs)and mRNAs in the liver tissues were examined using high-throughput sequencing.Additionally,functional enrichment analysis and immune infiltration prediction were performed.The miRNA-mRNA regulatory axis was elucidated using the starBase database.Protein expression was evaluated using immunohistochemistry.RESULTS GTPs alleviated DHEP-induced liver dysfunction,blood lipid dysregulation,fatty liver disease,liver fibrosis,and mitochondrial and endoplasmic reticulum lesions in mice.The infiltration of macrophages,mast cells,and natural killer cells varied between the model and treatment groups.mmu-miR-141-3p(a differentially expressed miRNA),Zcchc24(a differentially expressed mRNA),and Zcchc24(a differentially expressed protein)constituted the miRNA-mRNA-protein regulatory axis involved in mediating the therapeutic effects of GTPs on DEHP-induced liver damage in mice.CONCLUSION This study demonstrated that GTPs mitigate DEHP-induced liver dysfunction,blood lipid dysregulation,fatty liver disease,and partial liver fibrosis,and regulate immune cell infiltration.Additionally,an important miRNAmRNA-protein molecular regulatory axis involved in mediating the therapeutic effects of GTPs on DEHP-induced liver damage was elucidated.
文摘Pharmaceutical companies that produce gastrointestinal(GI)medications often utilize phthalates for their ability to localize medication release.Commonly prescribed GI medications that may utilize phthalates are 5-Aminosalicylates,proton pump inhibitors,and pancreatic enzymes.Our understanding of the cumulative health effects of phthalates from medications remains unclear,and there is increasing evidence that phthalates are not harmless.Experimental studies in animals have shown that phthalates,specifically dibutyl phthalate and Di-(2-ethyl-hexyl)phthalate,have the potential to alter and/or inhibit reproductive biology and in utero development.Despite the lack of definitive human data,many cohort and cross-sectional studies demonstrate concerning associations between phthalates and poor health status,specifically developmental problems.Longitudinal studies and studies with larger sample sizes are required to determine whether phthalates actually cause negative health consequences.It is also important that physicians regularly review and discuss with patients the medicinal ingredients in their medications and supplements,specifically in pregnant woman with inflammatory bowel disease.
文摘Phthalates have been used in a wide variety of consumer goods. Their versatility as plasticizers has translated into worldwide use in a vast array of consumer products. These compounds can leach into matrices, such as food and liquids that can be routed for human exposure. One of the most used phthalates is Diethylhexyl phthalate (DEHP). Diethylhexyl phthalate and its metabolite 2-ethyl-1-hexanol (2-EH) have demonstrated biological effects which merit further evaluation. In this work, we expand on our previous work with DEHP and screen the 2-EH metabolite for different cell death endpoints such as growth inhibition, apoptosis, autophagy, caspase activation, DNA fragmentation, and cell cycle arrest using fluorophores and the NC3000 instrument. Significant results (p 0.05) revealed higher toxicity for the 2-EH metabolite when compared to DEHP. Also, 2-EH presented apoptosis induction with characteristic hallmarks, such as loss of mitochondrial membrane potential, caspase activation, DNA fragmentation and cell cycle arrest at the S phase. In addition, the presence of autophagosome was detected through L3CB protein staining. We conclude that 2-EH presents differences in cell death endpoints that interestingly differ from the DEHP parent compound. Further studies are needed to establish the molecular pathways responsible for the observed effects.
文摘Human beings are increasingly exposed to phthalates,which are a group of chemicals used to make plastics more flexible and harder to break,and simultaneously ingesting abundant food emulsifiers via daily diet.The purpose of this study was to investigate the effect of the food emulsifier glycerin monostearate(GMS)on male reproductive toxicity caused by di(2-ethylhexyl)phthalate(DEHP,one of the phthalates)and explore the underlying mechanism.Thirty male Sprague-Dawley rats were randomly divided into control group,DEHP group and DEHP+GMS group.Rats in the DEHP group and DEHP+GMS group were orally administered with 200 mg/kg/d DEHP with or without 20 mg/kg/d GMS.After 30 days of continuous intervention,it was found that the serum testosterone level was significantly lowered in DEHP group and DEHP+GMS group than that in control group(P<0.01).The serum testosterone level and the relative testis weight were significantly decreased in the DEHP+GMS group as compared with those in the DEHP group and control group(P<0.05).More spermatids were observed to be shed off in DEHP+GMS group than in DEHP group.The expression levels of cell cycle checkpoint kinase 1(Chkl),cell division cycle gene 2(Cdc2),and cyclin-dependent kinase 2(CDK2)were down-regulated in DEHP group,and this tendency was more significant in DEHP+GMS group(P<0.05 or P<0.01).There was no significant difference in the P-glycoprotein(P-gp)expression between DEHP group and control group.However,P-gp was markedly down-regulated in DEHP+GMS group(P<O.Ol).The results indicated that the food emulsifier GMS aggravated the toxicity of DEHP on male reproduction by inhibiting the cell cycle of testicular cells and the expression of P-gp in testis tissues.
基金the National Natural Science Foundation of China(Grant no.81373045)the Provincial Natural Science Foundation of Hubei of China(Grant no.2015CFA139)
文摘Hexafluoroisopropanol(HFIP)-induced sodium dodecyl sulfate/dodecyltrimethylammonium bromide(SDS/DTAB) catanionic surfactant coacervate extraction method coupled with high performance liquid chromatography(HPLC) was used to detect the migration of phthalates from disposable tablewares to drinking water. The concentration factors are larger than 82 and extraction recoveries over 53% for water samples spiked with 100 or 200 ng/m L phthalates. Limit of detection is in the range of 1.0–2.6 ng/m L.Good linearity with correlation coefficients larger than 0.9985 is obtained in the concentration of20–1500 or 40–3000 ng/m L. Relative recoveries are from 82.4% to 123.6% for water samples spiked with30/60, 250/500, and 1500/3000 ng/m L phthalates, respectively. Relative standard deviations(RSDs) are0.4%–7.4% for intraday precision(n = 5) and 0.6%–7.8% for interday precision(n = 3). Four of studied phthalates are found in the drinking water samples prepared from four kinds of tablewares.
基金financial support of Department of Pharmaceutics, Faculty of Pharmacy, Kerman Medical Science University
文摘This paper describes the electrodeposition of polyphosphate-doped polypyrrole/nanosilica nano-composite coating on steel wire for direct solid-phase microextraction of bisphenol A and five phthalates. We optimized influencing parameters on the extraction efficiency and morphology of the nanocomposite such as deposition potential, concentration of pyrrole and polyphosphate, deposition time and the nanosilica amount. Under the optimized conditions, characterization of the nanocomposite was inves-tigated by scanning electron microscopy and Fourier transform infra-red spectroscopy. Also, the factors related to the solid-phase microextraction method including desorption temperature and time, extrac-tion temperature and time, ionic strength and pH were studied in detail. Subsequently, the proposed method was validated by gas chromatography-mass spectrometry by thermal desorption and acceptable figures of merit were obtained. The linearity of the calibration curves was between 0.01 and 50 ng/mL with acceptable correlation coefficients (0.9956-0.9987) and limits of detection were in the range 0.002-0.01 ng/mL. Relative standard deviations in terms of intra-day and inter-day by five replicate analyses from aqueous solutions containing 0.1 ng/mL of target analytes were in the range 3.3%-5.4% and 5%-7.1%, respectively. Fiber-to-fiber reproducibilities were measured for three different fibers prepared in the same conditions and the results were between 7.3% and 9.8%. Also, extraction recoveries at two different concentrations were ≥96%. Finally, the suitability of the proposed method was demonstrated through its application to the analysis of some eye drops and injection solutions.
基金supported by the National Natural Science Foundation of China [82073566 and 82073578]the Program for Excellent Young Talents in College and University of Anhui Province [gxyq2019014]+1 种基金the Clinical Scientific Research Project of Anhui Medical University [2020xkj161]the Anhui Medical University Clinical Pharmacology and Pharmacology Co-construction Project (2020)
文摘Objective Prenatal phthalate exposure has been associated with placental inflammatory factors and infant allergic rhinitis(AR).However,the results are inconclusive.We designed a population-based cohort study to examine the effects of placental inflammatory biomarkers on the sex-dependent associations between maternal phthalate exposure and infant AR.Methods A total of 2,348 pregnant women from Ma’anshan,Anhui Province,China,who were screened before antenatal visits and met the inclusion criteria,were included in the present study.We assessed AR in their offspring aged 36 months with a questionnaire.Quantitative PCR was performed to measure placental inflammatory factor m RNAs.The independent samples t-test and multivariable logistic regression were used to determine the associations between infant AR and maternal phthalates.Results Childhood AR may be related to education and family monthly income(P = 0.01).The phthalate metabolites,mono(2-ethylhexyl) phthalate(MEHP),mono(2-ethyl-5-hydroxyl) phthalate(MEHHP),in pregnant women were associated with a significantly increased risk for infant AR in males[P < 0.05;odds ratio(OR):1.285;95% confidence interval(CI):1.037-1.591,and OR:1.232,95% CI:1.008-1.507,respectively],but not females.Additionally,irritably-increased expression levels of HO-1 and IL-4 were associated with AR in male infants(OR:1.175;95% CI:1.038-1.329 and OR:1.181;95% CI:1.056-1.322,respectively).The association between maternal urinary MEHHP and placental HO-1 was marginally significant according to mediation analysis.Conclusion The associations of maternal MEHHP and MEOHP levels with fetal AR in males were significant.Placental HO-1 was a fractional mediator in the associations between MEHHP and AR.Thus,the placenta should be further investigated as a potential mediator of maternal exposure-induced disease risk in children.
文摘The objective of this study was to determine the concentrations of the metabolites of four selected phthalates, widely used industrial chemicals which possess endocrine-disrupting properties, in samples of amniotic fluid and maternal urine collected in the same day, in order to verify if the latter can be considered a measure of the fetal exposure. The quantitative determination of the metabolites was carried out by HPLC-MS/MS with isotopic dilution from 70 pregnant volunteers. Detectable concentrations of phthalates metabolites were found in amniotic fluids. As phthalate monoesters are excreted in the urine conjugated with glucuronic acid, an enzymatic hydrolysis is carried out before analysis. Amniotic fluids were tested with and without hydrolysis and only the free phthalate metabolites, not conjugated with glucuronic acid, were found. The concentration of metabolites after enzymatic hydrolysis in maternal urine is not correlated to those of amniotic fluids, but the free form concentrations are. These results suggest that only the free forms can cross the placenta. A significant number of mothers showed urine phthalate monoesters concentrations higher than non-pregnant women.
基金supported by the National Natural Science Foundation of China(No.31470543)
文摘This study investigated the occurrence and distribution of 15 phthalate esters(PAEs) in sediments collected from Qixinghe wetlands, northeast China. Total concentration of PAEs in all sediments ranged from 128.41 to 502.79 μg kg^(-1), with the mean value of 284.61 μg kg^(-1).PAEs significantly differed among wetland types; the average PAEs concentration of surface sediments were as follows: Phragmites australis wetland(PAW, 419.87 ±73.61 μg kg^(-1)) [ Carex lasiocarpa wetland(CLW,304.18 ± 56.47 μg kg^(-1)) [ Deyeuxia angustifolia wetland(DAW, 129.78 ± 18.24 μg kg^(-1)). Dimethyl phthalate(DMP), diisobutyl phthalate, di-n-butyl phthalate, and di-(2-ethylhexyl) phthalate(DEHP) were found in all sediments,DEHP was the most abundant PAEs congeners with concentrations varying from 37.62 to 294.9 μg kg^(-1). DMP and DEHP exhibited relatively higher concentrations in CLW and PAW wetlands than in DAW, indicating that the different deoxidization and biodegradation conditions could have important implications for the distribution patterns of PAEs in wetland sediments. The variation of PAEs concentrations in horizontal and vertical sediments with wetland types could be attributed to the migration of contaminants by surface water, groundwater and atmospheric deposition. The occurrence and distribution of PAEs in wetlands also sμggests that contamination in natural ecosystems should not be overlooked.
文摘The biodegradation of dimethyl phthalate(DMP)was investigated under fermentative conditions in this study.The nature of the intermediate compounds and the extent of mineralization were probed using high-pressure liquid chromatography(HPLC)and liquid chromatography-mass spectrometry(LC-MS)methods.The fermentative bacteria were able to biodegrade the DMP under anaerobic conditions,with the biodegradation rate of 0.36 mg DMP/(L·h).The results demonstrated that the DMP degradation under fermentative conditio...
基金supported by the National Natural Science Foundation of China [Grant No.81273079].
文摘Objective Di-(2-ethylhexyl) phthalate(DEHP) is a ubiquitous environmental contaminant.As an endocrine disruptor,it seriously threatens human health and ecological environmental safety.This study examines the impact of intervention with soybean isoflavones(SIF) on DEHP-induced toxicity using a metabonomics approach.Methods Rats were randomly divided into control(H),SIF-treated(A,86 mg/kg body weight),DEHP-treated(B,68 mg/kg),and SIF plus DEHP-treated(D) groups.Rats were given SIF and DEHP daily through diet and gavage,respectively.After 30 d of treatment,rat urine was tested using UPLC/MS with multivariate analysis.Metabolic changes were also evaluated using biochemical assays.Results Metabolomics analyses revealed that p-cresol glucuronide,methyl hippuric acid,N1-methyl-2-pyridone-5-carboxamide,lysophosphatidycholine [18:2(9 Z,12 Z)] {lyso PC [18:2(9 Z,12 Z)]},lyso PC(16:0),xanthosine,undecanedioic acid,and N6-acetyl-l-lysine were present at significantly different levels in control and treatment groups.Conclusion SIF supplementation partially protects rats from DEHP-induced metabolic abnormalities by regulating fatty acid metabolism,antioxidant defense system,amino acid metabolism,and is also involved in the protection of mitochondria.
基金supported by the National Natural Science Foundation of China(No.81571508 and No.81771654)the National Natural Science Youth Foundation of China(No.81701520)the Self-dependent Innovation Research Funding of Huazhong University of Science and Technology(No.2017KFYXJJ121)。
文摘Ovary plays an important role in the female reproductive system.The maintenance and regulation of ovarian function are affected by various physical and chemical factors.With the development of industrialization,environmental pollutants have caused great harm to public health.Phthalates,as a class of endocrine-disrupting chemicals(EDCs),are synthesized and used in large quantities as plasticizers due to their chemical properties.They are easily released into environment because of their noncovalent interactions with substances,causing human exposure and possibly impairing ovary.In recent years,more and more attention has been paid to the role of epigenetics in the occurrence and development of diseases.And it is urgent to study the role of methylation,gene imprinting,miRNA,and other epigenetic mechanisms in reproductive toxicology.
文摘This study represents, detailly, the validated method for the extraction and quantification of widespread phthalic acid esters (PAEs) bis(2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DBP) and di-n-octyl phthalate (DnOP) from solitary ascidians collected from a marine environment. The extraction was based on a pressurized liquid extraction method, using n-hexane as the solvent to extract the target PAEs from dry biological tissues, and was performed in an accelerated solvent extraction instrument. The average recovery of 89.2% was obtained from samples subjected to a pressure of ~1500 psi and 120°C in two 10-min cycles. GC-MS was used for quantification, conducted in single-ion monitoring mode. Following careful and rigorous cleanup procedures to prevent cross-contamination from laboratory glassware, PAE standards showed signals with good specificity. The obtained limits of detection were 130, 122 and 89 ng/g for DEHP, DBP and DnOP, respectively. Accordingly, the calculated limits of quantification were 394, 370 and 270 ng/g for DEHP, DBP and DnOP, respectively. The obtained linearity ranged from 5.4 to 269 ng/ml (equivalent to 135 - 6725 ng/g dry weight), with R2 ≥ 0.998. Concentrations in the range of 200 to 9000 and 400 to 5000 ng/g sample dry weight, for DEHP and DBP, respectively, were obtained from the ascidians. No DnOP was detected in any of the samples. These results indicate that the method presented in this study is applicable for detection of low and trace concentrations of the target PAEs in samples collected from a marine organism, which can serve as a bioindicator of plastic contamination.
文摘Medical wastes have been implicated in river pollution in developing countries and most often people depend on water from such rivers for sources of livelihood. Phthalates (endocrine disruptors) are major components in medical wastes and are commonly found contaminants in aquatic environment. Most sewage treatment facilities handling medical waste are inefficient due to overuse and poor maintenance and discharge directly into rivers. This study aimed to investigate the identity and estimates the concentration of phthalates in supposed treated medical wastes from a hospital sewer and water from a receiving river. Samples were randomly collected before and after treatment by the sewer plants, while samples were randomly collected along the course of the river starting from point of discharge. Control samples were taken from upstream about 500 m along the river course. The samples were extracted by liquid-liquid chroma- tographic process using dichloromethane, after which they were cleaned up in a column of silica gel using hexane as the mobile solvent. The cleaned extracts were analyzed by HPLC. The concentrations (μg/L) of dimethyl-, diethyl-, diphenyl-, dibutyl- and di-(2-ethyl)hexyl phthalates ranged from 62.81 ± 18.53;4.74 ± 3.57;2.05 ± 1.80;11.40 ± 5.58 to 141.92 ± 35.8 respectively in the sewer waste. The receiving river had a concentration (μg/L) of 9.17 ± 14.02;0.18 ± 0.31;0.48 ± 0.84;2.84 ± 1.21;61.72 ± 38.35 respectively for dimethyl-, diethyl-, diphenyl-, dibutyl- and di-(2-ethyl) hexyl phthalates. These concentrations were higher than control and far exceeded the USEPA limits of 3 μg/l recom- mended for phthalates in water. Contaminants of aquatic environment by untreated wastes from hospitals has serious implications on public health and environment as human risks for phthalate esters downstream are high and this calls for urgent need to develop strategy to build incentives for compliance in treatment and discharge of wastes into river waters.
文摘Immunity is crucial to the health of animals and it can determine their survival and fitness. Di(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer and hence is the most abundant phthalate in the environment. Exposure to DEHP is of great concern for human health. In the present study, we tested the hypothesis that exposure to DEHP would suppress T cell-mediated immunity in mice. Twenty adult male Kunming mice were randomly assigned into the control (n = 10) and the DEHP treatment (n = 10) groups. Both groups have free access to food and water, while the mice in the latter group drank DEHP solution (2000 mg/L) for 42 days. T cell-mediated immunity assessed by phytohaemagglutinin (PHA) response was depressed in the DEHP treated mice compared with the controls, however, wet thymus and spleen mass, white blood cells were not influenced by DEHP treatment. Taken together, different immunological parameters responded differently to DEHP treatment in Kunming mice.
文摘Our previous studies revealed the polycyclic aromatic hydrocarbon and phthalic acid esters were the major organic pollutants in the Jialing River and Yangtze River in the Three Gorges area, and they might cause the toxicity in male fertility when combined. Thus we used di-n-butyl phthalate (DBP) and Benzo(a)pyrene (Bap) as their representatives respectively to explore their effects on the spermatogenesis in male rats. Male Sprague Dawley rats were randomly divided into 4 groups and respectively exposed to corn oil, Bap (5 mg/kg/d), DBP (250 mg/kg/d), and combined doses of Bap (5 mg/kg/d) and DBP (250 mg/kg/d) for 90 days. We observed a significant increase in the stillbirth rate after Bap and combined treatments, while the mean area of seminiferous tubules was reduced after Bap, DBP and combined treatments. Bap and combined treatment had a sup- pressing effect on meiosis in germ cells, which reduced the haploid contents and the ratio between haploid and diploid but increased the tetraploid and diploid contents and the ratio between hap- loid and tetraploid. These effects were more obvious in the combined group. Furthermore, the ex- pression of a number of proteins was changed, of which was associated with the oxidative stress and cAMP/PKA signaling pathway. Our results suggest that Bap has significant toxic effects on male fertility, while the combined treatment of Bap and DBP has more toxic effects.
