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ENVIRONMENTAL POLLUTION · 2017 · IF 5.099

A novel nuclear xenobiotic receptors (AhR/PXR/CAR)-mediated mechanism of DEHP-induced cerebellar toxicity in quails (Coturnix japonica) via disrupting CYP enzyme system homeostasis

Zheng-Hai Du,Jun Xia,Xiao-Chen Sun,Xue-Nan Li,Cong Zhang,Hua-Shan Zhao,Shi-Yong Zhu,Jin-Long Li

Di-(2-ethylhexyl)-phthalate (DEHP) is causing serious health hazard in wildlife animal and human through environment and food chain, including the effect of brain development and impacted neurobehavioral outcomes. However, DEHP exposure caused cerebellar toxicity in bird remains unclear. To evaluate DEHP-exerted potential neurotoxicity in cerebellum, male quails were exposed with 0, 250, 500 and 750 mg/kg BW/day DEHP by gavage treatment for 45 days. Neurobehavioral abnormality and cerebellar histopathological alternation were observed in DEHP-induced quails. DEHP exposure increased the contents of total Cytochrome P450s (CYPs) and Cytochrome b5 (Cyt b5) and the activities of NADPH-cytochrome c reductase (NCR) and aniline-4-hydeoxylase (AH) in quail cerebellum. The expression of nuclear xenobiotic receptors (NXRs) and the transcriptions of CYP enzyme isoforms were also influenced in cerebellum by DEHP exposure. These results suggested that DEHP exposure caused the toxic effects of quail cerebellum. DEHP exposure disrupted the cerebellar CYP enzyme system homeostasis via affecting the transcription of CYP enzyme isoforms. The cerebellar P450arom and CYP3A4 might be biomarkers in evaluating the neurotoxicity of DEHP in bird. Finally, this study provided new evidence that DEHP-induced toxic effect of quail cerebellum was associated with activating the NXRs responses and disrupting the CYP enzyme system homeostasis.

CAS / MDL: 117-81-7
研究领域: 环境毒理学 · 神经毒理学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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SCIENCE OF THE TOTAL ENVIRONMENT · 2018 · IF 4.61

Discrimination of typical cyclic compounds and selection of toxicity evaluation bioassays for coal gasification wastewater (CGW) based on toxicity mechanism of actions (MOAs)

Mengqi Zheng,Yuxing Han,Chunyan Xu,Hongjun Han,Zhengwen Zhang

This paper originally investigated toxicity discrimination of typical cyclic compounds and bioassays selection on toxicity evaluation for coal gasification wastewater (CGW) effluent with mechanism-oriented investigation. Initially, representative cyclic toxicants were selected and classified with quantitative structure–toxicity relationship (QSTR). Nitrogen heterocyclic compounds (NHCs) and polycyclic aromatic hydrocarbons (PAHs) were basically discriminated as nonpolar narcotics with significant correlation to hydrophobicity ( p  < 0.05, R 2  = 0.8668–0.9635), while phenols were regarded as polar narcotics and reactive compounds due to slight correlation to hydrophobicity ( p  > 0.05, R 2  < 0.5). Furthermore, specific mechanism of actions (MOAs) to various organisms revealed that phenols were discriminated as critical source of acute toxicity in CGW, with short-term visible and irreversible damage. However, NHCs and PAHs, which exerted accumulation toxicity rather than acute toxicity, might result in potential mutagenicity and unpredictable risk along the food chain. Afterwards, based on species sensitivity to typical toxicants and application in real CGW effluent, non-applicability of Chlorella vulgaris ( C. vulgaris ) was validated in toxicity evaluation. While Daphnia magna ( D. magna ) was suggested as a toxicity bioassay in entire effluent due to the highest sensitivity and applicability. Tetrahymena thermophile ( T. pyriformis ) might be applicable in effluent with low biodegradability due to similar evaluation results (TU = 8.90) to D. magna (TU = 6.67) in aerobic effluent. Finally, the relationship between toxicity and bioavailability based on typical pollutants and model species illustrated necessity for dualism toxicity-biodegradability investigation on CGW.

研究领域: 环境科学 · 毒理学
✓ 已验证 DOI 高影响因子
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JOURNAL OF HAZARDOUS MATERIALS · 2024 · IF 12.2

Pigmentiphaga kullae CHJ604 improved the growth of tobacco by degrading allelochemicals and xenobiotics in continuous cropping obstacles

Jia-Xi Xiong,Ling-Shan Du,Na-Na Li,Xiu-Ting Wu,Yang Xiang,Sha Li,Lei Zou,Dongqi Liu,Duo Huang,Ze Feng Xie,Ying Wang,Jinhua Li,Jingcheng Dai,Dazhong Yan,Hong-Jun Chao

Plant autotoxicity is considered to be one of the important causes of continuous cropping obstacles in modern agriculture, which accumulates a lot of allelochemicals and xenobiotics and is difficult to solve effectively. To overcome tobacco continuous obstacles, a strain Pigmentiphaga kullae CHJ604 isolated from the environment can effectively degrade these compounds in this study. CHJ604 strain can degrade 11 types of autotoxicity allelochemicals and xenobiotics (1646.22 μg/kg) accumulated in the soil of ten-years continuous cropping of tobacco. The 11 allelochemicals and xenobiotics significantly reduced Germination Percentage (GP), Germination Index (GI), and Mean Germination Time (MGT) of tobacco seeds, and inhibited the development of leaves, stems, and roots. These negative disturbances can be eliminated by CHJ604 strain. The degradation pathways of 11 allelochemicals and xenobiotics were obtained by whole genome sequence and annotation of CHJ604 strain. The heterologous expression of a terephthalate 1,2-dioxygenase can catalyze 4-hydroxybenzoic acid, 4-hydroxy-3-methoxybenzoic acid, 4-hydroxybenzaldehyde, and 4-hydroxy-3-methoxy-benzaldehyde, respectively. The phthalate 4,5-dioxygenase can catalyze phthalic acid, diisobutyl phthalate, and dibutyl phthalate. These two enzymes are conducive to the simultaneous degradation of multiple allelochemicals and xenobiotics by strain CHJ604. This study provides new insights into the biodegradation of autotoxicity allelochemicals and xenobiotics as it is the first to describe a degrading bacterium of 11 types of allelochemicals and xenobiotics and their great potential in improving tobacco continuous obstacles.

CAS / MDL: 88-99-3
研究领域: 植物学 · 微生物学 · 农业科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2022 · IF 5.895

Time-Series-Dependent Global Data Filtering Strategy for Mining and Profiling of Xenobiotic Metabolites in a Dynamic Complex Matrix: Application to Biotransformation of Flavonoids in the Extract of Ginkgo biloba by Gut Microbiota

Hui-Ying Wang,Cheng Qu,Meng-Ning Li,Chao-Ran Li,Run-Zhou Liu,Zifan Guo,Ping Li,Wen Gao,Hua Yang

Efficient characterization of xenobiotic metabolites and their dynamics in a changing complex matrix remains difficult. Herein, we proposed a time-series-dependent global data filtering strategy for the rapid and comprehensive characterization of xenobiotic metabolites and their dynamic variation based on metabolome data. A set of data preprocessing methods was used to screen potential xenobiotic metabolites, considering the differences between the treated and control groups and the fluctuations over time. To further identify metabolites of the target, an in-house accurate mass database was constructed by potential metabolic pathways and applied. Taking the extract of Ginkgo biloba (EGB) co-incubated with gut microbiota as an example, 107 compounds were identified as flavonoid-derived metabolites (including 67 original from EGB and 40 new) from 7468 ions. Their temporal metabolic profiles and regularities were also investigated. This study provided a systematic and feasible method to elucidate and profile xenobiotic metabolism.

研究领域: 代谢组学 · 药理学 · 计算生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY · 2022 · IF 5.785

DEHP triggers a damage severity grade increase in the jejunum in quail (Coturnix japonica) by disturbing nuclear xenobiotic receptors and the Nrf2-mediated defense response

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.

CAS / MDL: 117-81-7
研究领域: 毒理学 · 鸟类生物学 · 环境科学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY · 2024 · IF 4.2

Polystyrene microplastics with absorbed nonylphenol induce intestinal dysfunction in human Caco-2 cells

Fangfang Ding,Huimei Wang,Yingzhi Li,Xueping Leng,Jiaming Gao,Danfei Huang

Due to the massive production and use of plastic, the chronic and evolving exposure to microplastics in our daily lives is omnipresent. Nonylphenol (NP), a persistent organic pollutant, may change toxicity when it co-exists with microplastics. In this study, polystyrene microplastics (PS-MPs), either alone or with pre-absorbed NP, generated oxidative stress and inflammatory lesions to Caco-2 cells, as well as affecting proliferation via the MAPK signaling pathway and causing apoptosis. Damage to cell membrane integrity and intestinal barrier (marked by lower transepithelial electric resistance, greater bypass transport, and tight junction structural changes) leads to enhanced internalization risk of PS-MPs. Some important intestinal functions including nutrient absorption and xenobiotic protection were also harmed. It is worth noting that the exposure of PS-MPs with a diameter of 0.1 μm improved intestinal functions quickly but acted as a chemosensitizer for a long time, inhibiting cell perception of other toxic substances and making the cells more vulnerable.

研究领域: 环境科学 · 毒理学 · 细胞生物学 · 胃肠病学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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