CHEMOSPHERE
·
2022
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IF 8.943
Yingjie Liu,Zhongxiang Chen,Shanwei Li,Lu Ding,Xiaofeng Wei,Shicheng Han,Peng Wang,Yanchun Sun
Di-(2-ethylhexyl) phthalate (DEHP) is one of the most extensively utilized plasticizers in the plastic manufacturing process. It is widely used in various fields due to its low cost and excellent effect. Although there is evidence that DEHP is harmful to animal and human health, DEHP-induced gill toxicity in aquatic organisms is inconclusive, and its mechanism has not been fully elucidated. Here, we investigated the effects of DEHP acute exposure on crucian carp gills at environmentally relevant concentrations of 20, 100, and 500 μg/L. Multi-omics profiling and biochemical assays were employed to characterize the potential toxicological mechanisms. The results showed that acute exposure to 100 and 500 μg/L of DEHP leads to oxidative stress in gills, as evidenced by overproduction of reactive oxygen species (ROS), increased antioxidant enzyme activity , and the transformation of glutathione from reduced to oxidized form, resulting in lipid peroxidation. Integrative analysis of transcriptomics and metabolomics indicated that increased purine metabolism was the potential source of increased ROS. Moreover, lipid metabolism disorder, including arachidonic acid metabolism, induces inflammation. Further, DEHP causes the imbalance of the CYP enzyme system in the gill, and DEHP-induced gill toxicity in crucian carp was associated with interference with CYP450 homeostasis . Taken together, this study broadens the molecular understanding of the DEHP-induced gill toxicity in aquatic organisms and provides novel perspectives for assessing the effects of DEHP on target and non-target aquatic organisms in the environment.
研究领域:
环境毒理学
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水生生物学
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分子生物学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Autophagy
·
2026
·
IF 18.6
Si-Yu Yu,Qiao Liu,Yao-Hua Gu,Wen-Zhuo Han,Ao-Jing Han,Jun Xiong,Tian-Zhou Li,Qiu-Shuang Hu,Fang-Ying Gang,Chen-Qian Zhao,Tian Feng,Jianbo Tian,Xiaoping Miao,Xue-Jie Yu,Neng-Bin Xie,Bi-Feng Yuan
Di(2-ethylhexyl) phthalate (DEHP) is a widely used industrial plasticizer, raising global concerns due to its potential endocrine-disrupting effects and environmental persistence. Human exposure to DEHP primarily occurs through the ingestion of contaminated food and water, inhalation of airborne particles, and dermal contact with products containing DEHP. Understanding the toxicological mechanisms of DEHP is essential for evaluating its health risks and developing effective strategies to mitigate its adverse effects. In this study, we conducted long-term exposure experiments to DEHP using both an animal model and in vitro system to investigate the complex interplay among DNA methylation, hyperactivation of macroautophagy/autophagy, mitochondrial dysfunction, and lipid accumulation induced by DEHP. The results revealed that DEHP exposure induced the degradation of DNMT1 (DNA methyltransferase 1) by enhancing its interaction with the autophagy-related protein SQSTM1 (sequestosome 1). DNMT1 degradation resulted in decreased methylation of the promoter regions of genes associated with autophagosome formation, subsequently increasing their expression. The resulting demethylation excessively activated autophagy, contributing to mitochondrial dysfunction and lipid accumulation in the liver. This study uncovered a previously unrecognized interplay among hyperactivation of autophagy, mitochondrial dysfunction, and lipid accumulation in the context of DEHP exposure. These findings enhanced our understanding of DEHP’s toxicity and underscored concerns about the long-term health effects of environmental pollutants, particularly regarding metabolic diseases.Abbreviation: ATG5:autophagy related 5; ATG16L1: autophagy related 16 like 1; BECN1:beclin 1; COX4/COXIV: cytochrome c oxidase subunit 4; BS-seq:bisulfite sequencing; DCFH-DA: 2′,7′-dichlorodihydrofluoresceindiacetate; DEHP: di(2-ethylhexyl) phthalate; DNMT1: DNAmethyltransferase 1; DNMT3A: DNA methyltransferase 3A; FABP4: fattyacid binding protein 4; FASN: fatty acid synthase; LPL: lipoproteinlipase; MAP1LC3/LC3: microtubule associated protein1 light chain 3; NAFLD: nonalcoholic fatty liver disease; NR1H3:nuclear receptor subfamily 1 group H member 3; PPARG: peroxisomeproliferator activated receptor gamma; RB1CC1: RB1 induciblecoiled-coil 1; SQSTM1: sequestosome 1; SREBF2: sterol regulatoryelement binding transcription factor 2; VDAC1: voltage dependentanion channel 1.
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2026
·
IF 6.2
Hong-Mei Zhu,Ming-Shan Chen,Muhammad Asmat Ullah Saleem,Jia-Xin Wang,Fu-Wei Jiang,Shuo Liu,Yu-Sheng Shi,Yi Zhao,Jin-Long Li
Di(2-ethylhexyl) phthalate (DEHP) is a commonly used plasticizer in polyvinyl chloride (PVC) products. The translocase of the outer mitochondrial membrane 70 (TOM70) mediates the import of various proteins into the mitochondria. This study aims to investigate the influence of DEHP on the nervous system and elucidate the potential protective role of TOM70 in microglia. Mice were administered DEHP at doses of 0, 50, 200, or 500 mg/kg for 28 days. DEHP reduced cortical cell counts, lowered cell density, and caused cell swelling, nuclear pyknosis, and mitochondrial damage in brain cells, with effects exacerbated in the D200 group and most severe in the D500 group. Further investigation revealed that DEHP inhibited TOM70 expression and suppressed the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. These findings suggest that TOM70 may be a potential target against DEHP-induced microglial neuroinflammation via mitochondrial damage. This study provides new insights into therapeutic strategies for tackling neurodegenerative diseases.
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2018
·
IF 3.974
Xue-Xue Chen,Yang Wu,Xian-Pei Huang,Huixiong Lü,Hai-Ming Zhao,Ce-Hui Mo,Hui Li,Quan-Ying Cai,Ming-Hung Wong
Di-(2-ethylhexyl) phthalate (DEHP) is a typical endocrine disrupting chemical with relatively high concentrations in agricultural soils of China. Here, a rhizobox experiment was conducted to investigate the variations in microbial community and DEHP dissipation among different soil rhizospheric compartments between low ( Fengyousimiao ) and high ( Peizataifeng ) DEHP-accumulating cultivars of rice ( Oryza sativa L.) grown in DEHP spiked soil (0, 20, 100 mg/kg). The dissipation rates of DEHP in rhizospheric soils of Peizataifeng were generally significantly higher than those of Fengyousimiao, with the highest removal rate in 0–2 mm rhizosphere. The results of Illumina-HiSeq high-throughput sequencing revealed that both bacterial and fungal diversity and community structure were significantly different in rhizospheric soils of the two cultivars. DEHP dissipation rates in 0–2 mm rhizosphere of Peizataifeng were positively correlated with bacterial and fungal diversity. The relative abundance of DEHP-degrading bacterial genera Acinetobacter, Pseudomonas and Bacillus of Peizataifeng was generally higher than those in the same rhizospheric compartment of Fengyousimiao in DEHP treatments, resulting in different rhizospheric DEHP dissipation. Cultivation of Peizataifeng in agricultural soil is promising to facilitate DEHP dissipation and ensure safety of agricultural products.
研究领域:
环境科学
·
微生物学
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2018
·
IF 3.974
Linbao Zhang,Ying Hu,Wei Sun,Si Chen,Xiaoping Jia,Wengui Cai
Di-(2-ethylhexyl) phthalate (DEHP) is currently the most frequently detected phthalic acid esters (PAEs) compounds and can induce diverse toxicities on aquatic organisms. To understand the molecular responses of fish to DEHP, we performed transcriptomic profiles in liver of tilapia ( Oreochromis niloticus ) which were exposed to environmental concentration of DEHP. A total of 30.10 Mb and 30.16 Mb clean reads were retrieved from the control and DEHP treated libraries, respectively. De-novo assembly of all the clean reads obtained 58,585 unigenes. After comparing the two libraries, 2814 and 1790 genes were identified as significantly increased and depressed, respectively. Gene ontology (GO) classification system and Kyoto Encyclopedia of Genes and Genomes (KEGG) database analysis demonstrated that DEHP significantly disturbed the expression level of genes associated with immunity, endocrine and reproductive system, lipid metabolism and so on. Quantitative real-time PCR was performed to validate the results of RNA-sequencing (RNA-seq) analysis. The resulting data provide new insights for exploring the molecular basis of tilapia response to DEHP exposure.
研究领域:
环境毒理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Environmental Sciences
·
2022
·
IF 6.796
Wenhui Zhang,Na Zheng,Sujing Wang,Siyu Sun,Qirui An,Xiaoqian Li,Zimeng Li,Yining Ji,Yunyang Li,Jiamin Pan
The production of face towels is growing at an annual rate of about 4% in China, reaching 1.13 million tons by 2021. Phthalates (PAEs) are widely used in textiles, and face towels, as an important household textile, may expose people to PAEs via the skin, further leading to health risks. We collected new face towels and analyzed the distribution characterization of PAEs in them. The changes of PAEs were explored in a face towel use experiment and a simulated laundry experiment. Based on the use of face towels by 24 volunteers, we calculated the estimated daily intake (EDI) and comprehensively assessed the hazard quotient (HQ), hazard index (HI), and dermal cancer risk (DCR) of PAEs exposure in the population. PAEs were present in new face towels at total concentrations of
研究领域:
环境科学
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公共卫生
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毒理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2022
·
IF 5.895
Ying-Xin Zhao,Yi-Xi Tang,Xiao-Han Sun,Shi-Yong Zhu,Xue-Yan Dai,Xue-Nan Li,Jin-Long Li
Di-(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer in plastic products, consumer products, and packaging materials. It is of great health concern in both animals and humans as it released into the environment and entered into the body from plastic products over time, thereby resulting in neurotoxicity. As a pivotal regulator of the central nervous system (CNS), astrocytes, are crucial for maintaining brain homeostasis. Nevertheless, the underlying reason for astrocyte neurotoxicity due to DEHP exposure remains incompletely understood. Here, using an in vivo model of neurotoxicity in quail, this study summarizes that Cx43 is internalized by phosphorylation and translocated to the nucleus as a consequence of DEHP exposure in astrocytes. This study further demonstrated that astrocytes transformed to pro-inflammatory status and induced the formation of autophagosomes. Of note, integrated immunofluorescent codetection approaches revealed an overexpression of the glial fibrillary acidic protein (GFAP) and down-expression of Cx43 in astrocytes. Therefore, in terms of neurotoxicity, this experiment in vivo models directly linked Cx43 internalization to autophagy and neuroinflammation and ultimately locked these changes to the astrocytes of the brain. These findings unveil a potential approach targeting Cx43 internalization for the treatment of neurodegeneration caused by DEHP exposure in astrocytes.
研究领域:
神经科学
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毒理学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2012
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IF 4.173
Rui Li,Chao Yu,Rufei Gao,Xueqing Liu,Jing Lu,Letian Zhao,Xuemei Chen,Yubin Ding,Yingxiong Wang,Junlin He
Di-(2-ethylhexyl)-phthalate (DEHP) is a ubiquitous environmental pollutant and endocrine disruptor (ED) that causes serious adverse effects on animal and human health. The harmful effects of DEHP on human reproduction are increasingly recognized, especially in women. However, it is not known how endometrial receptivity and embryo implantation, which play important roles in the establishment of pregnancy, are affected by DEHP. This study was aimed towards investigating the effects of DEHP on endometrial receptivity and embryo implantation in pregnant mice. The pregnant mice received DEHP at 0, 250, 500 and 1000 mg/kg/day from day 1 (D1) of gestation until sacrifice. Administration of DEHP led to compromised endometrial receptivity and decreased number of implantation sites. The mRNA and protein expression levels of ERα, PR and E-cadherin, but not those of HoxA10 and MMP-2, were up-regulated by DEHP in the mouse endometrium. The results further suggested that DEHP disrupts the MAPK and NF-κB signaling pathways. This was maybe one of paths which influenced the E-cadherin expression. In conclusion, DEHP reduced endometrial receptivity and impaired embryo implantation by influencing the expression of hormone receptors and E-cadherin. Therefore, determining the full extent of the hazards of DEHP to human reproduction will be vital to developing and implementing effective protective measures.
研究领域:
生殖生物学
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毒理学
·
分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Ning-Ning Huang,Ping-An Jian,Jia-Yu Du,Wen-Na Cai,Tian-Ning Yang,Zhi-Juan Wang,Shi-Yong Zhu,Kai Guo,Jin-Long Li,Chi-Chiu Wang,Xue-Nan Li
Global health issues have been heightened by di-(2-ethylhexyl) phthalate (DEHP), a commonly utilized plasticizer, due to its liver toxicity and potential to cause liver damage. Ferroptosis, a type of nonapoptotic cell death reliant on iron, is associated with multiple liver disorders. This research aimed to explore the role and mechanisms of ferroptosis in DEHP-induced liver toxicity in chickens. In vivo experiments showed that DEHP exposure caused liver damage. Transcriptomic analysis revealed that DEHP exposure activated ferroptosis and significantly upregulated myo-inositol oxygenase (MIOX) expression. Subsequent in vitro experiments using LMH cells revealed that reducing MIOX levels diminished ferroptosis caused by mono- (2-ethylhexyl) phthalate (MEHP), DEHP’s main metabolite, through the stimulation of the STAT3 signaling pathway. Our findings highlight the important role of MIOX in DEHP-induced liver injury via STAT3 signaling pathway. This study provides new evidence that MIOX is a potential therapeutic target for iron toxicosis associated liver diseases.
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DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2025
·
IF 11.3
Liping Tan,Rufei Gao,Yan Su,Yan Zhang,Yanqing Geng,Qiuju Liu,Yidan Ma,Xuemei Chen,Fangfang Li,Junlin He
Phthalate-induced female reproductive health issues, particularly those related to di (2-ethylhexyl) phthalate (DEHP), are growing global concerns. Although most studies have focused on single-generation exposure, studies on prolonged DEHP exposure across multiple generations are limited. This study assessed the effects of multigenerational DEHP exposure on endometrial decidualization , which is crucial for embryo implantation . The results showed that sustained DEHP exposure over three generations exacerbated decidualization injury and led to adverse pregnancy outcomes. RNA sequencing revealed upregulation of the imprinted gene Snurf in the decidua , with changes that may not depend on alterations in DNA methylation . Knockdown of Snurf significantly alleviated in vitro decidualization deficiency induced by mono(2-ethylhexyl) phthalate (MEHP), the biologically active metabolite of DEHP. Proteomic analysis and the AlphaFold 3 algorithm indicated that Stn1 is a downstream target of Snurf , with silencing Stn1 resensitizing Snurf -knockdown stromal cells to MEHP. Human decidual stromal cells (hDSCs) from healthy participants showed sensitivity to MEHP, with the inhibition of decidualization. Epidemiological data from the 2017–2018 National Health and Nutrition Examination Survey (NHANES) indicated a positive association between DEHP exposure and female infertility . This study highlighted the cumulative toxic effects of multigenerational DEHP exposure on female reproduction and revealed the contribution of imprinted genes.
研究领域:
毒理学
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生殖生物学
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表观遗传学
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环境健康
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2026
·
IF 6.7
Li Muzi,Zhao Ruyang,Wang Qiqian,Chen Jing,Ma Xiaoyang,Wang Haoran,Li Jinlong
Di(2-ethylhexyl) phthalate (DEHP)
is a widespread environmental
pollutant with neurotoxicity, while lycopene (LYC) is a neuroprotective
dietary carotenoid. This study investigated whether LYC alleviates
DEHP-induced brain injury by regulating microglial activation and
cGAS-STING signaling. ICR mice were treated with LYC (5 mg/kg) and/or
DEHP (500 mg/kg) for 28 days, with results validated in BV2 cells.
In vivo, DEHP exposure impaired spatial learning and memory, triggered
neuronal degeneration, microglial activation and mitochondrial dysfunction,
increased 2 ′ 3 ′ -cGAMP production, and activated cGAS-STING
signaling. LYC supplementation markedly reversed these changes. Network
toxicology, molecular docking, and molecular dynamics suggested cGAS
as a potential LYC target. In vitro, MEHP-induced M1 polarization
was attenuated by LYC, and cGAS silencing verified the pathway’s
critical role in LYC’s protection. These findings indicate
that LYC alleviates DEHP-induced neural damage by maintaining mitochondrial
homeostasis and inhibiting cGAS-STING-mediated microglial activation,
providing a potential nutritional strategy for preventing brain damage
caused by environmental pollutants.
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高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Mu-Zi Li,Yi Zhao,Hao-Ran Wang,Milton Talukder,Jin-Long Li
Di (2-ethylhexyl) phthalate (DEHP) is an environmentally persistent and bioaccumulative plasticizer. Accumulation of DEHP in the body can eventually cause kidney damage. As a type of natural carotenoid, lycopene (LYC) has a potential protective effect on renal cells, but the protective mechanism has not yet been elucidated. The major goal of this study was to see how effective LYC was at treating DEHP-induced nephrotoxicity in mice. ICR mice were treated with DEHP (500 mg/kg BW/day or 1000 mg/kg BW/day) or LYC (5 mg/kg BW/day) for 28 days. Through histopathology and ultrastructure, we found that LYC attenuated DEHP-induced renal tubular cell and glomerular damage. LYC relieved DEHP-induced kidney injury evidenced by lower levels of blood urea nitrogen (Bun), creatinine (Cre), and uric acid (Uric). Meanwhile, the reduced expression of kidney injury molecule-1 (Kim-1) also supported it. Notably, LYC can alleviate the activity or content of cytochrome P450 system (CYP450s) interfered with by DEHP. In addition, LYC treatment reduced nuclear accumulation of DEHP-induced aromatic hydrocarbon receptor (AhR) and AhR nuclear transporter (Arnt), and its downstream target genes such as cytochrome P450-dependent monooxygenase (CYP) 1A1, 1A2, and 1B1 expression significantly decreased to normal in the LYC treatment group. In summary, LYC can mediate the AhR/Arnt signaling system to prevent kidney toxicity in mice caused by DEHP exposure.
研究领域:
毒理学
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药理学
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分子生物学
·
环境健康
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）