SCIENCE OF THE TOTAL ENVIRONMENT
·
2024
·
IF 8.2
Xiaoping Liang,Jiehua Liang,Shengqi Zhang,Haowei Yan,Tiangang Luan
Di-2-ethylhexyl phthalate (DEHP), a widely utilized plasticizer , has been described as a potential obesogen based on in vivo disruption of hepatic lipid homeostasis and in vitro promotion of lipid accumulation. However, limited literature exists regarding the specific ramifications of DEHP exposure on obese individuals, and the precise mechanisms underlying the adverse effects of DEHP exposure remain unclear. This study aimed to assess the impact of DEHP on hepatic lipid metabolism in obese mice by comparing them to normal mice. Following a 10-week DEHP exposure period, the obese mice exhibited higher blood lipid levels, more severe hepatic steatosis, and more infiltrations of inflammatory cells in liver tissue than normal mice. Interestingly, the body weight of the mice exhibited no significant alteration. In addition, transcriptomic analyses revealed that both lipogenesis and fatty acid oxidation contributed to hepatic lipid metabolism dysregulation following DEHP exposure. More specifically, alterations in the transcription of genes associated with hepatic lipid metabolism were linked to the different responses to DEHP exposure observed in normal and obese mice. Additionally, the outcomes of in vitro experiments validated the in vivo findings and demonstrated that DEHP exposure could modify hepatic lipid metabolism in normal mice by activating the LXR/SREBP-1c signaling pathway to promote lipogenesis. At the same time, DEHP exposure led to inhibition of the Camkkβ/AMPK pathway to suppress β -fatty acid oxidation. Conversely, in obese mice, DEHP exposure was found to be associated with the stimulation of both lipogenesis and fatty acid oxidation via activation of the LXR/SREBP-1c and PPAR-α signaling pathways, respectively. The findings presented in this study first elucidate the contrasting mechanisms underlying DEHP-induced liver damage in obese and normal mice, thereby offering valuable insights into the pathogenesis of DEHP-induced liver damage in individuals with obesity.
研究领域:
毒理学
·
肝病学
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分子生物学
·
肥胖研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2020
·
IF 6.793
Yanluo Xie,Huakang Liu,Hao Li,Hao Tang,He Peng,Heng Xu
Di-(2-ethylhexyl) phthalate (DEHP) has been classified as a priority pollutant which increased the healthy risk to human and animals dramatically. Hence, a novel biochemical system combined by DEHP-resistant bacterial flora (B) and a green oxidant of persulfate (PS) activated by Nano-Fe 3 O 4 was applied to degrade DEHP in contaminated soil. In this study, the resistant bacterial flora was screened from activated sludge and immobilized by sodium alginate (SAB). Nano-Fe 3 O 4 was coated on biochar (BC@Fe 3 O 4 ) to prevent agglomerating in soil. X-ray diffraction (XRD) and scanning electron microscope (SEM) were utilized to characterize BC@Fe 3 O 4 . Results demonstrated that the treatment of biochemical system (SAB + BC@Fe 3 O 4 + PS) presented the maximum degradation rate about 92.56% within 24 days of incubation and improved soil microecology. The 16S rDNA sequences analysis of soil microorganisms showed a significantly different abundance and a similar diversity among different treatments. Kyoto Encyclopedia of Genes and Genomes (KEGG) functional genes difference analysis showed that some metabolic pathways, such as metabolism of cofactors and vitamins, energy metabolism, cell growth and death, replication and repair, were associated with the biodegradation of DEHP. Besides, DEHP was converted to MEHP and PA by biodegradation, while DEHP was converted to DBP and PA by persulfate and BC@Fe 3 O 4 , and then ultimately degraded to CO 2 and H 2 O.
研究领域:
环境科学
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微生物学
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土壤学
·
基因组学
✓ 已验证
DOI
PubMed
高影响因子
GeroScience
·
2024
·
IF 5.3
Cao Haiming,Xie Qigen,Luo Peng,Chen Jiaqi,Xia Kai,Ma Lin,Chen Demeng,Deng Chunhua,Wan Zi
Di-(2-ethylhexyl) phthalate (DEHP), a prevalent plasticizer, is known to have endocrine-disrupting effects on males and cause reproductive toxicity. There were causal effects of DEHP on testosterone levels in the real world by Mendelian randomization analysis. Exposure to DEHP during the preadult stage might lead to premature testicular senescence, but the mechanisms responsible for this have yet to be determined. In this study, we administered DEHP (300 mg/kg/day) to male C57BL/6 mice from postnatal days 21 to 49. The mice were kept for 6 months without DEHP. RNA sequencing was conducted on testicular tissue at PNM6. The results indicated that DEHP hindered testicular development, lowered serum testosterone levels in male mice, and induced premature testicular senescence. TM3 Leydig cells were exposed to 300 μM of mono(2-ethylhexyl) phthalate (MEHP), the bioactive metabolite of DEHP, for 72 h. The results also found that DEHP/MEHP induced senescence in vivo and in vitro. The mitochondrial respiratory chain was disrupted in Leydig cells. The expression and stability of STAT5B were elevated by MEHP treatment in TM3 cells. Furthermore, p-ERK1/2 was significantly decreased by STAT5B, and mitochondria-STAT3 (p-STAT3 ser727) was significantly decreased due to the decrease of p-ERK1/2. Additionally, the senescence level of TM3 cells was decreased and treated with 5 mM NAC for 1 h after MEHP treatment. In conclusion, these findings provided a novel mechanistic understanding of Leydig cells by disrupting the mitochondrial respiratory chain through STAT5B-mitoSTAT3.
研究领域:
毒理学
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内分泌学
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生殖生物学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Cachexia Sarcopenia and Muscle
·
2022
·Vol. 13
·期 6
·2740-2751
·
IF 12.063
Fengju Li,Ting Luo,Honghui Rong,Lu Lu,Ling Zhang,Chuanfeng Zheng,Dali Yi,Yi Peng,Enyu Lei,Xiaotao Xiong,Fengchao Wang,Jose M. Garcia,Ji-an Chen
Background Di-(2-ethylhexyl) phthalate (DEHP) and its metabolites can cross the placenta and may cause birth defects and developmental disorders. However, whether maternal DEHP exposure affects skeletal muscle development in the offspring and the pathways involved are unknown. This study investigated the effects of maternal DEHP exposure and the contribution of myostatin (MSTN) to skeletal muscle development in the offspring. Methods Pregnant wild-type and muscle-specific myostatin knockout (MSTN KO) C57BL/6 mice were randomized to receive vehicle (corn oil) or 250 mg/kg DEHP by gavage every other day until their pups were weaned (postnatal day 21 [PND21]). Body weights of the offspring mice were measured longitudinally, and their hindleg muscles were harvested at PD21. Also, C2C12 cells were treated with mono-2-ethylhexyl phthalate (MEHP), the primary metabolite of DEHP, and proteolysis, protein synthesis, and myogenesis markers were measured. The contribution of myostatin to maternal DEHP exposure-induced muscle wasting in the offspring was determined. Results Maternal DEHP exposure reduced body weight growth, myofibre size, and muscle mass in the offspring compared to controls (Quad: 2.70 ± 0.1 vs. 3.38 ± 0.23, Gastroc: 2.29 ± 0.09 vs. 2.81 ± 0.14, Tibialis: 1.01 ± 0.07 vs. 1.25 ± 0.11, mg/tibial length in mm, all P < 0.01, n = 35). Maternal DEHP exposure significantly increased Myostatin expression (2.45 ± 0.41 vs. 0.03 ± 0.00 DEHP vs. controls, P < 0.01, n = 5), Atrogin-1(2.68 ± 0.65 vs. 0.63 ± 0.01, P < 0.05, n = 5), MuRF1 (1.56 ± 0.51 vs. 0.31 ± 0.01, P < 0.05, n = 5), and Smad2/3 phosphorylation (4.12 ± 0.35 vs. 0.49 ± 0.18, P < 0.05), and decreased MyoD (0.27 ± 0.01 vs. 1.52 ± 0.01, P < 0.05, n = 5), Myogenin (0.25 ± 0.03 vs. 1.95 ± 0.56, P < 0.05, n = 5), and AKT phosphorylation (4.12 ± 0.35 vs. 1.00 ± 0.06, P < 0.05, n = 5), in skeletal muscle of the offspring in MSTN flox/flox , but not in MSTN KO mice. Maternal DEHP exposure resulted in up-regulation of CCAAT/enhancer-binding protein δ (C/EBPδ, 4.12 ± 0.35 vs. 1.00 ± 0.19, P < 0.05, n = 5) in skeletal muscle of the offspring in MSTN flox/flox and MSTN KO mice (4.12 ± 0.35 vs. 4.35 ± 0.28, P > 0.05, n = 5). In vitro, C/EBPδ silencing abrogated the MEHP-induced increases in Myostatin, MuRF-1, and Atrogin-1 and decreases in MyoD and Myogenin expression. Conclusions Maternal DEHP exposure impairs skeletal muscle development in the offspring by enhancing the C/EBPδ-myostatin pathway in mice.
研究领域:
发育生物学
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毒理学
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肌肉生理学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ACS Pharmacology & Translational Science
·
2021
·
IF 0
Xue-Yan Dai,Shi-Yong Zhu,Mu-Zi Li,Milton Talukder,Yi Zhao,Jin-Long Li
Di(2-ethylhexyl) phthalate (DEHP) is a synthetic chemical and widely used as a plasticizer. Humans can be exposed to DEHP through direct contact or environmental contamination. Lycopene (Lyc) has been discussed as a potential effector in the prevention and therapy of various diseases. 140 male mice were assigned into control, vehicle control, Lyc (5 mg/kg BW/d), DEHP (500 and 1000 mg/kg BW/d, respectively), and DEHP + Lyc groups and treated with an oral gavage that lasted 28 d. The ultrastructural results showed that DEHP induced pathological changes and mitochondrial injuries. We further revealed that DEHP exposure destroyed the Fe2+ imbalance homeostasis and, consequently, increases of lipid peroxidation and inhibition of cysteine/glutamate antiporter, all of which were involved in the process of ferroptsis. Moreover, the supplementation of Lyc significantly inhibited the ferroptsis changes mentioned above. Altogether, these results indicated that DEHP exposure triggered splenic cell death via ferroptosis; meanwhile, they also shed new evidence on a potential clue for the intervention and prevention of DEHP-related diseases.
研究领域:
毒理学
·
药理学
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细胞生物学
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环境健康
✓ 已验证
产品关联
DOI
PubMed
SCIENCE OF THE TOTAL ENVIRONMENT
·
2020
·
IF 6.551
Chenhui Duan,Yanjun Fang,Jingran Sun,Zhenxin Li,Qiangqiang Wang,Jialei Bai,Hui Peng,Jun Liang,Zhixian Gao
The health risks of exposure to plasticizers have received widespread attention, however, little is known about the effects of fast food packaging plasticizers on steroid hormone synthesis. In the present study, the types and migration of plasticizers in some commonly used fast-food packaging materials were detected by GC–MS, and the interference effects of these plasticizers and their metabolites on steroid hormone synthesis in the human body were evaluated by the H295R steroidogenesis assay. The GC–MS results showed that the main plasticizer compounds that migrated from fast food packaging into food were di(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and bis(2-ethylhexyl) adipate (DEHA). Exposure to these chemicals (100–1000 μM) can significantly reduce the viability of H295R cells in a dose-response manner, and these plasticizers and their metabolites that migrated into oily foods at high temperatures (0.25–25 μM) could significantly increase the E2 level and reduce the T level in H295R cells. According to the qRT-PCR data, 0.25 to 25 μM mono(2-ethylhexyl) phthalate (MEHP) significantly upregulated the expression levels of 17β-HSD1 and CYP19A1, and downregulated those of CYP17A1, CYP11A1 and StAR. The Western blot results were consistent with those of qRT-PCR. In summary, these results indicated that even exposure to low concentrations (≤1 mg/l or 2.5 μM) of these chemicals and their metabolites can cause significant endocrine-disrupting effects.
研究领域:
环境健康
·
毒理学
·
内分泌学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2018
·
IF 4.358
Yi Zhao,Zheng-Hai Du,Milton Talukder,Jia Lin,Xue-Nan Li,Cong Zhang,Jin-Long Li
The widely used Di-(2-ethylhexyl) phthalate (DEHP) has been reported to exhibit ubiquitous environmental and global health hazards. The bioaccumulation and environmental persistence of DEHP can cause serious health hazards in wildlife animals and human. However, DEHP-induced nephrotoxicity in bird is remained unknown. Thus, this study explored the related mechanism of DEHP nephrotoxicity in quail. For this purpose, quail were exposed with DEHP at doses of 0, 250, 500, and 1000 mg/kg body weight daily by gavage administration for 45 days. The results showed that DEHP exposure induced renal injury, oxidative stress , and endoplasmic reticulum (ER) degeneration. Low level DEHP (250 mg/kg) exposure inhibited Nrf2 signaling pathway and induced renal injury via oxidative stress and suppressed the unfolded protein response (UPR) signaling pathway and induced ER stress in the kidney. But surprisingly, high level DEHP (500 mg/kg and 1000 mg/kg) exposure activated Nrf2 and UPR signaling pathways and protected kidney, but they still couldn't resist the toxicity of DEHP. Our study demonstrated that DEHP-induced nephrotoxicity in quail was associated with activating Nrf2-mediated antioxidant defense response and UPR signaling pathway.
研究领域:
毒理学
·
环境科学
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分子生物学
·
动物生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL BIODETERIORATION & BIODEGRADATION
·
2022
·
IF 4.907
Xiaoyong Song,Zihan Zhang,Yanran Dai,Deshou Cun,Baihui Cui,Yuewei Wang,Yaocheng Fan,Haibin Tang,Liang Qiu,Feihua Wang,Dongru Qiu,Wei Liang
Di-(2-ethylhexyl) phthalate (DEHP), the most extensively used phthalate acid esters (PAEs), poses a potential risk to human and environment. A novel bacterial strain , Rhodococcus sp. LW-XY12, with efficient PAE-degrading capability, was isolated from activated sludge. Strain LW-XY12 could degrade 96.91 ± 0.68% of DEHP (500 mg L −1 ) within 32 h. The degradation curves of DEHP (50–1500 mg L −1 ) and PAE mixture (500 mg L −1 each) fitted well with the modified Gomperz kinetics model. DEHP metabolic pathway was reconstructed by using genome annotation and metabolic intermediate analyses. The DEHP metabolic pathway might comprise de-esterification and β-oxidation. Homologous modeling and molecular docking analysis revealed that DEHP and MEHP (mono-(2-ethylhexyl) phthalate) could be bound to putative carboxylesterase (KXC42_04905) via hydrogen bonding and hydrophobic interaction. A conserved catalytic triad (Ser195-Glu319-His412) might act as an active protein pocket and catalyze the hydrolysis of DEHP. Carboxylesterase (KXC42_04905) could hydrolyze ester bond and a possible mechanism underlying ester bond hydrolysis catalyzed by the carboxylesterase was proposed. Protocatechuate 3,4-dioxygenase, 3-oxoadipate CoA-transferase, benzoate 1,2-dioxygenase, catechol 1,2-dioxygenase, and catechol 2,3-dioxygenase transcripts were detected and significantly up-regulated under DEHP induction. This study sheds light on the functional genes associated with DEHP degradation and metabolic mechanism in this versatile bacterium for degradation of PAEs.
研究领域:
环境微生物学
·
基因组学
·
生物降解
·
生物化学
✓ 已验证
产品关联
DOI
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2024
·
IF 6.2
Pan Song,Dong Lv,Luchen Yang,Jing Zhou,Xin Yan,Zhenghuan Liu,Kai Ma,Yunfei Yu,Xiaoyang Liu,Qiang Dong
Di-(2-ethylhexyl) phthalate (DEHP) might led to chronic and long-term effects on human organs due to its widespread use and bioaccumulation. Despite some cohorts reporting an association between DEHP exposure and BPH, its underlying mechanisms have not been investigated. Our findings indicate that exposure to DEHP or MEHP (main metabolites of DEHP in the human body) leads to increased prostate weights, elevated prostate index, and notable epithelial thickening in rats. It has been observed to promote BPH-1 cell proliferation with effects ranging from low to high concentrations. Transcriptome sequencing analysis of rat prostate tissues identified KIF11 as the key hub gene. KIF11 is highly expressed after DEHP/MEHP exposure, and knocking down of KIF11 inhibits the MEHP-induced promotion of cell proliferation. Exposure to MEHP has been observed to increase the expression of p-GSK-3β and elevate the levels of β-catenin, thereby activating the Wnt/β-catenin signaling pathway. Knocking down of KIF11 significantly inhibits these effects. Histone H3 at Lysine 27 acetylation (H3K27ac) is implicated in the upregulation of KIF11 expression, as evidenced by the addition of the acetylation inhibitor C646. In summary, our findings established that DEHP exposure could promote BPH through H3K27ac regulated KIF11/Wnt/β-catenin signaling pathway.
研究领域:
毒理学
·
分子生物学
·
内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2024
·
IF 6.2
Jinzhu Meng,Lilin Xiao,Qiuye Li,Ling Gong,Ping Luo,Yuanyuan Zhao,Shuilian Wang
Di-(2-ethylhexyl) phthalate (DEHP), an endocrine-disrupting chemical present in plasticized products, exerts strong modulation on the anatomy and function of the female reproductive system. However, the potential mechanisms underlying DEHP-induced regulation of prepubertal female reproductive toxicity have not yet been elucidated. Therefore, this study was designed to elucidate the molecular mechanism of ovarian injury induced by DEHP exposure in mice. Elevated serum mono-2-ethylhexyl phthalate (MEHP) concentrations, decreased levels of ovarian hormones (E2 and P4), and observed ovarian injury were found after DEHP exposure. Ovarian transcriptome analysis revealed significant alterations in ferroptosis-associated gene expression, with potential regulation by Nrf2. Subsequent analysis of ferrous iron, malondialdehyde (MDA), Western blotting, and immunofluorescence of the ovaries confirmed the RNA-seq findings. Transcriptome analysis of granulosa cells revealed a direct or indirect regulatory relationship between Nrf2 and downstream ferroptosis-related proteins following MEHP exposure. Further experiments demonstrated that ferrostatin-1 attenuated MEHP-induced ferroptosis in granulosa cells. Additionally, Nrf2 stabilization and accumulation in the nucleus of granulosa cells were observed following MEHP treatment. RNAi-mediated knockdown of Nrf2 exacerbated MEHP-induced ferroptosis in granulosa cells. This evidence indicates that DEHP exposure induces ferroptosis through regulation of the Nrf2-mediated signaling pathway in mouse ovaries, laying the groundwork for future studies aiming to develop therapeutic strategies against DEHP toxicity.
研究领域:
生殖毒理学
·
分子生物学
·
内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2020
·
IF 9.038
Xia Li,Jianpeng Li,Sijia Hao,Ailing Han,Yayu Yang,Guozhen Fang,Jifeng Liu,Shuo Wang
Di(2-ethylhexyl) phthalate (DEHP), the most abundantly used plasticizer, was considered to be a hazardous chemical that was difficult to be degraded naturally. In this study, inspired by the “catalytic triad’’ in serine proteases, an enzyme mimic material was developed by combining the proteases’s active sites of serine, histidine and aspartate (S-H-D) with the self-assembling sequence of LKLKLKL and the aromatic group of fluorenylmethyloxycarbonyl (Fmoc). By mixing the monomer of peptides containing separate S, H and D residues with a ratio of 2:1:1, the enzyme mimics were found to co- assemble into nanofibers (Co-HSD) and showed the highest activity towards DEHP degradation because of the synergistic effects of active sites, orderly secondary structure and stable molecular conformation. To further improve ability and applicability, the high active mimetic enzyme was immobilized onto regenerated cellulose (RC) membranes for DEHP degradation in a continuous recycling mode. The RC membranes were first functionalized by the NaIO 4 oxidation method to form aldehyde groups and then conjugated with the enzyme mimics via Schiff-base reaction. As a biocatalytic membrane, this membrane could not only effectively degrade DEHP, but also showed good stability, thus establishing a promising biomaterial for large scale biodegradation of DEHP in water decontamination and liquid food depollution.
研究领域:
环境科学
·
生物技术
·
材料科学
·
水处理
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2021
·Vol. 12
·期 10
·4582-4590
·
IF 5.396
Xue-Yan Dai,Yi Zhao,Jing Ge,Shi-Yong Zhu,Mu-Zi Li,Milton Talukder,Jin-Long Li
Lycopene (Lyc) has been discussed as a potential effector in the prevention and therapy of various diseases. Di(2-ethylhexyl) phthalate (DEHP) is regarded as a universal environmental pollutant. To clarify the potential protective effect of Lyc on DEHP-induced splenic injury, 140 male mice were randomized into seven groups: control (distilled water), vehicle control (corn oil per day), Lyc (5 mg per kg BW per day), DEHP (500 or 1000 mg per kg BW per day), and DEHP combined Lyc group, respectively. All experimental animals were treated by oral gavage for 28 days. The results that showed DEHP exposure significantly up-regulated the mRNA and protein expression of the sirtuin family (except SIRT4-5), PGC-1α, OPA1, Drp1, MFN1/2, NRF1, TFAM, Parkin and PINK in DEHP-treated alone groups and the SOD2 and LC3-II protein expression were also in accordance with the above changes. These were accompanied with an increase of the number of inflammatory cells and rate of mitochondrial damage, and autophagosome formation in the spleen. Notably, Lyc supplementation facilitated all these changes to effectively return to the normal level, indicating that Lyc exerts protective effects against DEHP-induced splenic toxicity. Altogether, the protective effects of Lyc may be a strategy to ameliorate DEHP-induced spleen damage.
研究领域:
毒理学
·
药理学
·
分子生物学
·
免疫学
✓ 已验证
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）