INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
·
IF 7.7
Lijuan Zhang,Shan Sun,Wentao Su,Mingqian Tan
The present study was to investigate the effect of the astaxanthin high internal phase Pickering emulsion (H-AXT) on DEHP-induced liver lipid metabolism disorder and to demonstrate its possible protective mechanism. We have developed an antioxidant activity emulsion system to deliver astaxanthin into the liver to maximize its ability to protect the liver. In vitro , H-AXT intervention inhibited oxidative stress restored the level of mitochondrial membrane potential to 90 % of that of normal LO2 cells, and alleviated the imbalance of energy metabolism by protecting mitochondrial structure and function. Based on metabonomics, it was proved that H-AXT inhibited triglyceride accumulation by antagonizing lipid metabolism disorder. In DEHP-induced mice, H-AXT intervention mitigated liver damage by inhibiting oxidative stress and inflammatory reaction, and alleviated metabolic dysfunction by regulating lipid levels and inhibiting fat accumulation. Meanwhile, H-AXT alleviated DEHP-induced testicular tissue damage and maintained the integrity of testicular tissue. The encapsulation of the emulsion system effectively promoted the liver uptake of astaxanthin to prevent liver diseases associated with metabolic disorders.
研究领域:
食品科学
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生物医学
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营养学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
·
2022
·
IF 5.785
Tian-Ning Yang,Xue-Nan Li,Xiao-Wei Li,Jin-Yang Li,Yue-Qiang Huang,Jin-Long Li
As a plasticizer , di-2-ethylhexyl phthalate (DEHP) has been listed as a potential endocrine disruptor by The World Health Organization. The toxicity of DEHP has been widely studied, but its toxicity on the digestive tract of birds has not been clarified. Female quail were treated by gavage with DEHP (250, 500, 750 mg/kg), with the blank and vehicle control groups reserved. The result showed that DEHP raised the damage severity grade, and decreased the ratio of villus length to crypt depth. The content and activity of cytochrome P450 system (CYP450s) were increased by DEHP. DEHP interfered with the transcription of nuclear xenobiotic receptors (NXRs), CYP isoforms, and the nuclear factor-E2-related factor 2 (Nrf2) signaling pathway. This study revealed DEHP could cause the imbalance in CYP450s mediated by NXRs, and then promote Nrf2 mediated antioxidant defense. This study provided new evidence about the mechanisms of DEHP-induced toxic effects on digestive tract.
研究领域:
毒理学
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鸟类生物学
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环境科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2023
·
IF 9.8
Xuyang Chai,Luyao Wen,Yuanyuan Song,Xiaochong He,Jingxian Yue,Jianlin Wu,Xin Chen,Zongwei Cai,Zenghua Qi
Phthalate esters (PAEs) are one of the significant classes of emerging contaminants that are increasingly detected in environmental and human samples. Nevertheless, the current toxicity studies rarely report how PAEs affect the cardiovascular system, especially in obese individuals. In this study, diet-induced obese mice and corresponding normal mice were exposed to di(2-ethylhexyl) phthalate (DEHP) by oral gavage at environmentally relevant concentrations and key characteristics of cardiovascular risk were examined. The 16S rRNA and high-resolution mass spectrometry were used to investigate the alterations in the gut microbial profile and metabolic homeostasis. The results indicated that the cardiovascular system of fat individuals was more susceptible to DEHP exposure than mice in the lean group. 16S rRNA-based profiling and correlation analysis collectively suggested DEHP-induced gut microbial remodeling in fed a high-fat diet mice, represented by the abundance of the genus Faecalibaculum . Using metagenomic approaches, Faecalibaculum rodentium was identified as the top-ranked candidate bacterium. Additionally, metabolomics data revealed that DEHP exposure altered the gut metabolic homeostasis of arachidonic acid (AA), which is associated with adverse cardiovascular events. Finally, cultures of Faecalibaculum rodentium were treated with AA in vitro to verify the role of Faecalibaculum rodentium in altering AA metabolism. Our findings provide novel insights into DEHP exposure induced cardiovascular damage in obese individuals and suggest that AA could be used as a potential modulator of gut microbiota to prevent related diseases.
研究领域:
毒理学
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微生物学
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心血管科学
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环境健康
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代谢组学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Chaoyu Huang,Chen Qian,Zongxian Li,Yuanyuan Qin,Wuning Mo,Faquan Lin
Ethnopharmacological relevance Rosa roxburghii is an ethnic medicinal herb. Folk medicine collections have documented its nourishing and strengthen effects. It has been used to improve reproductive health, but scientific evidence supporting its efficacy and mechanisms remains limited. Aim of this study Endocrine-disrupting chemicals, such as di-(2-ethylhexyl) phthalate (DEHP), are known to impair male reproductive health. This study aims to investigate the protective effects of raw Rosa roxburghii juice (RRJ) on DEHP-induced reproductive toxicity in mice and elucidates its underlying mechanisms. Materials and methods Using a DEHP-induced murine model of reproductive damage, we evaluated the effects of RRJ on sperm quality, testicular histopathology, reproductive endocrine function, oxidative stress, inflammation, apoptosis, and DNA damage. Network pharmacology analysis was performed to identify the active components, targets, and mechanisms underlying the therapeutic effects of Rosa Roxburghii . Results Our data demonstrated that RRJ significantly improved sperm quality, alleviated testicular atrophy, restored endocrine disorders, and mitigated oxidative stress, inflammation, and apoptosis in testicular tissues. Additionally, RRJ reduced testicular and sperm DNA damage, as evidenced by decreased γ-H2AX expression and DNA fragmentation index. Network pharmacology analysis identified quercetin, apigenin, luteolin, kaempferol, eriodictyol, and ellagic acid as the key bioactive compounds in RRJ, with the PI3K/AKT signaling pathway playing a crucial role in its therapeutic effects. Western blotting confirmed that RRJ reversed DEHP-induced suppression of the PI3K/AKT pathway. Conclusions This study demonstrates that RRJ protects against DEHP-induced reproductive toxicity through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms, mediated in part by the PI3K/AKT signaling pathway. This work provides the first comprehensive evidence of the protective effects of Rosa roxburghii against male reproductive system damage and its underlying mechanisms.
研究领域:
民族药理学
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生殖健康
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
EMBO Molecular Medicine
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2024
·
IF 9
WangHuiting,ZhaoZiting,SongMingming,ZhangWenxiang,LiuChang,ChenSiyu
Di-(2-ethylhexyl) phthalate (DEHP), an environmental pollutant, has been widely detected in both environmental and clinical samples, representing a serious threat to the homeostasis of the endocrine system. The accumulation of DEHP is notably pronounced in the liver and can lead to liver damage. The lack of effective high-throughput screening system retards the discovery of such drugs that can specifically target and eliminate the detrimental impact of DEHP. Here, by developing a Cy5-modified single-strand DNA-aptamer-based approach targeting DEHP, we have identified luteolin as a potential drug, which showcasing robust efficacy in detoxifying the DEHP by facilitating the expulsion of DEHP in both mouse primary hepatocytes and livers. Mechanistically, luteolin enhances the protein degradation of hepatic urocanate hydratase 1 (Uroc1) by targeting its Ala270 and Val272 sites. More importantly, trans-urocanic acid (trans-UCA), as the substrate of Uroc1, possesses properties similar to luteolin by regulating the lysosomal exocytosis through the inhibition of the ERK1/2 signal cascade. In summary, luteolin serves as a potent therapeutic agent in efficiently detoxifying DEHP in the liver by regulating the UCA/Uroc1 axis.
研究领域:
药理学
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毒理学
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分子生物学
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环境科学
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产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2018
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IF 4.427
Hui Wang,Xue-Nan Li,Peng-Cheng Li,Wei Liu,Zheng-Hai Du,Jin-Long Li
Di(2-ethylhexyl) phthalate (DEHP) is an omnipresent environmental pollutant with endocrine disrupting properties. As a plasticizer , DEHP can be leach from the plastic to transfer the external environment and thus enters the animal food chain, causing serious damage to the animal organs. The heat-shock response (HSR) comprising heat-shock protein (HSPs) and heat-shock transcription factor (HSFs) plays a pivotal role in various toxic stress conditions. For the sake of investigating the effects of DEHP exposure on cardiac toxicity and the regulation of HSR, male quail were fed the diet with 0, 250, 500 and 750 mg/kg DEHP by gavage administration for 45 days. Histopathological changes including cardiomyocyte swelling and muscle fiber dilatation were observed in the hearts exposed to DEHP. During the DEHP treatment, the mRNA expression of HSP60 and HSP70 were universally reduced, while the expression of other HSPs ( HSP10, HSP25, HSP27, HSP40, HSP47, HSP90, HSP110 ) had different degrees of growth. In addition, the levels of HSF1, HSF2, and HSF3 were significantly increased. Given the facts above, DEHP exposure induced the toxic effects of quail heart. DEHP exposure did great harm to HSR via affecting the synthesis of HSFs to mediate the transcription of the HSPs. Ultimately, this study provided new evidence that DEHP-induced cardiotoxicity in quail was related to activation of HSR and playing a protective role.
研究领域:
环境毒理学
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分子生物学
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心脏病学
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产品关联
DOI
PubMed
高影响因子
Obesity
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2015
·Vol. 24
·期 2
·368-378
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IF 3.734
Ziquan Lv,Jinquan Cheng,Suli Huang,Yanwei Zhang,Shuang Wu,Yangshen Qiu,Yijie Geng,Qian Zhang,Guanqin Huang,Quan Ma,Xing Xie,Shiquan Zhou,Tangchun Wu,Yuebin Ke
Objective Di(2-ethylhexyl) phthalate (DEHP) is reported to cause obesity and hypothyroidism in both humans and rodents, but the underlying mechanisms were largely unknown. This study was designed to clarify the effects and the mechanisms of DEHP on the pathogenesis of obesity and hypothyroidism and to discover the relationship between them. Methods Male C3H/He mice were treated with DEHP for 5 weeks, and the body weight, food intake, and body temperature were recorded during the exposure. After exposure, key organs and serum were analyzed by Q-PCR, Western blot, and ELISA. Results DEHP induced significant body weight gain and adipogenesis in all exposure groups except for 0.05 mg/kg. Marked hyperphagia and daytime hypothermia were also observed, which were accompanied by disturbed hypothalamic neuropeptide expression and reduced BAT UCP1 expression. In addition, WAT lipid metabolism was significantly deceased at low dose (0.5 mg/kg) and increased at high dose (50 and 200 mg/kg). DEHP also induced hypothyroidism, which was probably attributed to the combined effects of hepatic CAR activation and hypothalamic TRH inhibition induced by hypothalamic leptin resistance. Conclusions Chronic DEHP exposure could induce obesity by interrupting energy homeostasis, which is probably due to the synergistic effects of hypothyroidism and hypothalamic leptin resistance.
研究领域:
毒理学
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内分泌学
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代谢
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2015
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IF 4.529
Xinyi Mu,Xinggui Liao,Xuemei Chen,Yanli Li,Meirong Wang,Cha Shen,Xue Zhang,Yingxiong Wang,Xueqing Liu,Junlin He
Estrogen plays an essential role in the development of mammalian oocytes, and recent studies suggest that it also regulates primordial follicle assembly in the neonatal ovaries. During the last decade, potential exposure of humans and animals to estrogen-like endocrine disrupting chemicals has become a growing concern. In the present study, we focused on the effect of diethylhexyl phthalate (DEHP), a widespread plasticizer with estrogen-like activity, on germ-cell cyst breakdown and primordial follicle assembly in the early ovarian development of mouse. Neonatal mice injected with DEHP displayed impaired cyst breakdown. Using ovary organ cultures, we revealed that impairment was mediated through estrogen receptors (ERs), as ICI 182,780, an efficient antagonist of ER, reversed this DEHP-mediated effect. DEHP exposure reduced the expression of ERβ, progesterone receptor (PR), and Notch2 signaling components. Finally, DEHP reduced proliferation of pregranulosa precursor cells during the process of primordial folliculogenesis. Together, our results indicate that DEHP influences oocyte cyst breakdown and primordial follicle formation through several mechanisms. Therefore, exposure to estrogen-like chemicals during fetal or neonatal development may adversely influence early ovarian development.
研究领域:
生殖生物学
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内分泌学
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毒理学
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2024
·
IF 8.2
Jia-Gen Cui,Hao Zhang,Ming-Shan Chen,Jia-Xin Wang,Yi Zhao,Jin-Long Li
Phthalates (PAEs), especially di (2-ethylhexyl) phthalate (DEHP), are generally considered to have adverse impact on nervous system. The residue of DEHP in the environment has gradually become a widely concerned environmental problem due to its widespread use in plastic items. Lycopene (LYC) as the readily available natural antioxidant is considered to have the potential to alleviate exogenous poisons-induced nerve damage. However, there is currently a lack of strategies to alleviate the neurotoxicity caused by DEHP, and it is also unknown whether LYC can alleviate the neurotoxicity caused by DEHP. The experiment demonstrated that LYC had the potential to mitigate DEHP-induced mitochondrial damage in cerebellum. DEHP induced the disorder of Ca 2+ transport in cerebellum, thereby resulting in the imbalance of protein homeostasis. Such disruption in protein homeostasis further results in the overactivation of mitochondrial unfolded protein response (UPR mt ) and mitochondrial injury. Mechanistically, LYC could alleviate the imbalance of calcium homeostasis and protein homeostasis induced by DEHP via regulating inositol 1, 4, 5-trisphosphate receptor type1 (IP3R1) and sarco/endoplasmic reticulum Ca (2+)-ATPase 2 (SERCA2), further alleviating mitochondrial damage in cerebellum. Subsequently, the present study suggested the mechanism of cerebellar injury induced by DEHP, and provided a novel approach to treating DEHP-induced neurotoxicity.
研究领域:
神经科学
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毒理学
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药理学
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2024
·
IF 6.2
Jawad Ali Shah,Saif Ullah,Deyun Chen,Jianping Wu
Plastic mulching and organic amendments are prevalent agricultural practices worldwide. Plastic mulching has long been suspected as a significant source of DEHP contamination in terrestrial ecosystems. However, effects of DEHP contamination on greenhouse gas emissions and microbial biomass carbon (MBC) remain unclear. Here, a microcosm experiment was set up to assess the impact of DEHP exposure on MBC and carbon dioxide (CO 2 ) emission in two different soils (acidic and alkaline) with the inclusion of alfalfa straw. The treatment includes: (i) control with no amendment (T 1 ); (ii) alfalfa straw addition (20 g kg −1 ) (T 2 ); (iii) DEHP (10 mg kg −1 ) + alfalfa straw (T 3 ); and (iv) DEHP (100 mg kg −1 ) + alfalfa straw (T 4 ). Against the background of alfalfa inclusion, DEHP exposure led to a potential reduction in cumulative CO 2 emissions by 16.35 % and 6.91 % in alkaline soil and 12.27 % and 13.65 % in acidic soil for T 3 and T 4 , respectively. The addition of DEHP triggered CO 2 emissions and manifested a detrimental negative priming effect in both soil types. In both soils, average CO 2 emission fluxes were highest for the T 2 treatment. The MBC fluctuated at around 80 mg kg −1 for the control group, alfalfa straw alone (T 2 ) treatment considerably enhanced MBC contents, whereas DEHP contamination in T 3 and T 4 treatments suppressed the stimulatory effect of alfalfa on MBC in both alkaline and acidic soils. Furthermore, a positive relationship was observed between soil CO 2 emissions and MBC in both soils. Overall, these findings highlight the toxic impact of DEHP on MBC and its role in mitigating CO 2 emissions in diverse soils. DEHP exposure counters the CO 2 emissions induced by alfalfa straw. In addition, the inhibitory effect of DEHP on CO 2 fluxes in alkaline soil is less pronounced than in acidic soil. Therefore, further cutting-edge research is crucial since DEHP contamination poses serious ecological threats to agroecosystems.
研究领域:
环境科学
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微生物学
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DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
·
2017
·
IF 2.313
Nan Xiang,Chunfeng Zhao,Xiaoping Diao,Qian Han,Hailong Zhou
Di(2-ethylhexyl) phthalate (DEHP) is recognized as one of the most ubiquitous contaminants in marine environments and causes adverse effects on the health of marine organisms. The purpose of this study was to investigate the toxic effects of DEHP on the pearl oyster Pinctada martensii . The Pinctada martensii was exposed to 0.0, 0.5, 2, 8, or 32 mg L −1 DEHP for 7 and 10 days using parameters of antioxidant. Antioxidant indicators included levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), peroxidase (POD), and total antioxidant capacity (T-AOC) in the gills and hepatopancreas of Pinctada martensii for 7 and 10 days. Besides, we used the lowest observed effect concentration (LOEC) of five enzyme activities in different tissues of Pinctada martensii for 7 and 10 days to compare sensitivity. The results showed that the gills were more sensitive than the hepatopancreas of Pinctada martensii and that GSH activity in the gills and CAT activity in the hepatopancreas might be suitable biomarkers after 7 days of DEHP exposure. After 10 days of DEHP exposure, the GSH activity and CAT activity in the gills and SOD activity in the hepatopancreas could be regarded as biomarkers. Compared to the LOEC, GSH activity in the gills and CAT activity in the hepatopancreas after 7 days of DEHP exposure were more sensitive than any other biomarkers. In addition, after 10 days of DEHP exposure, GSH activity in the gills and hepatopancreas were much more sensitive than other activities. In conclusion, GSH activity demonstrated its potential to be used as a biomarker for the monitoring of DEHP pollution in the marine environment.
研究领域:
海洋生物学
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环境毒理学
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生态毒理学
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DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR ENDOCRINOLOGY
·
2025
·
IF 3.6
Lei Wei,Zonggang Feng,Qian Dou,Genhong Mao,Hu Zhao,Xinghua Zhao,Bin Hao
Male reproductive disorders are responsible for approximately 50% of infertility cases. Bis (2-ethylhexyl) phthalate (DEHP) is a common environmental pollutant known for its reproductive toxicity. Oxidative stress is a key mechanism in response to DEHP exposure. Glutathione S-transferase A2 (GSTA2), a member of the glutathione S-transferase family, has the capacity to detoxify environmental toxins. However, its role in regulating DEHP-induced male reproductive disorders remains unexplored. Next, male mice aged 3 weeks were orally administered with DEHP (500 mg/kg/day) for 14 days to induce male reproductive disorders. We observed a decrease in the GSTA2 expression in the testicular tissues of DEHP-treated mice. To investigate the role of GSTA2 in DEHP exposure, lentiviral vectors carrying GSTA2 sequences (1 × 10 7 TU/mL, 20 μL) were given to mice on the first day of DEHP treatment. GSTA2 overexpression was found to alleviate testicular damage induced by DEHP, as well as to inhibit oxidative stress and subsequent cell apoptosis. In addition, the PI3K/AKT signaling pathway, which is associated with oxidative stress and DEHP exposure, was activated in DEHP-exposed mice following GSTA2 overexpression. Subsequently, mouse spermatocyte GC-2spd cells with DEHP treatment were used to mimic male reproductive disorders in vitro . Consistently, the GSTA2 expression was decreased in GC-2spd cells with DEHP treatment. GSTA2 overexpression inhibited oxidative stress and cell apoptosis in DEHP-treated GC-2spd cells by activating the PI3K/AKT signaling pathway. Moreover, we discovered that GSTA2 overexpression significantly altered the metabolic profiles of DEHP-treated GC-2spd cells. Collectively, our results suggest that GSTA2 overexpression alleviates DEHP-induced male reproductive disorders by suppressing oxidative stress-mediated cell apoptosis via the PI3K/AKT signaling pathway, providing a novel insight into mitigating reproductive toxicity caused by DEHP exposure.
研究领域:
生殖毒理学
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分子生物学
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细胞生物学
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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）