ENVIRONMENTAL POLLUTION
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2025
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IF 7.3
Qiuhui Qian,Ji Wu,Cuizhen Wang,Zheng Yang,Ying Cheng,Yuansi Zheng,Xuedong Wang,Huili Wang
As a synthetic rubber antioxidant, the environmental monitoring concentrations of N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine (6-PPD) have exceeded the risk threshold, attracting widespread attention. Although investigations into the harmful effects on zebrafish have commenced, a comprehensive exploration of its toxicological impacts and underlying molecular mechanisms remains to be conducted. By using zebrafish as a model, this study systematically evaluated 6-PPD-induced lipid metabolism disorders and inflammation response following environmental exposure. Bioinformatics analysis revealed that 6-PPD target genes enriched in the hepatitis B pathway, indicating potential hepatic toxicity via inflammatory pathways. Therefore, we hypothesize that 6-PPD could trigger hepatotoxicity through the crosstalk between lipid metabolism and inflammation. Further experiments substantiated this hypothesis by showing lipid accumulation in the liver following 6-PPD exposure, along with elevated triglyceride (TG) and total cholesterol (TC) levels, and imbalanced expression of lipid metabolism-related marker genes. Additionally, 6-PPD exposure induced the accumulation of reactive oxygen species (ROS) and inhibited the differentiation and maturation of immune cells, resulting in immune evasion. Most of these abnormalities were exacerbated in a dose-dependent manner with increasing concentrations of 6-PPD. The addition of the PPARγ pathway agonist puerarin (PUE) or NF-κB pathway inhibitor quinazoline (QNZ) to 6-PPD exposure group mitigated these toxic effects, validating our conjecture that lipid metabolism disorder and inflammatory responses may result from the regulation of the PPARγ/NF-κB pathway.
研究领域:
环境毒理学
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分子生物学
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发育生物学
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免疫学
✓ 已验证
DOI
PubMed
高影响因子
Environmental Chemistry and Ecotoxicology
·
2025
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IF 8.2
Xin Wan,Geyu Liang,Dayong Wang
The 6-PPD quinone (6-PPDQ) is derived from 6-PPD, an antioxidant added in tires. Citric acid cycle plays a pivotal role in biochemical metabolisms. In Caenorhabditis elegans , we examined effect of 6-PPDQ exposure on citric acid cycle and the role of alteration in acetyl CoA and pyruvate contents during this process. In citric acid cycle, contents of intermediates were reduced by 0.1–10 μg/L 6-PPDQ. Meanwhile, expression of key enzyme genes ( cts-1 , idh-2 , dlst-1 , and dld-1 ) for citric acid cycle was decreased by 0.1–10 μg/L 6-PPDQ. After 6-PPDQ exposure, citric acid content was reduced by cts-1 RNAi, and NADH content was reduced by idh-2 , dlst-1 , and dld-1 RNAi. Exposure to 6-PPDQ (0.1–10 μg/L) further decreased acetyl CoA and pyruvate contents, and inhibited expression of enzyme genes ( dlat-1 and dld-1 ) governing acetyl CoA synthesis and enzyme genes ( pyk-1 and pyk-2 ) governing pyruvate synthesis. After 6-PPDQ exposure, dlat-1 and dld-1 RNAi reduced contents of acetyl CoA, citric acid, and NADH, and pyk-1 and pyk-2 RNAi reduced contents of pyruvate, citric acid, and NADH. In 6-PPDQ exposed nematodes, cts-1 , idh-2 , dlst-1 , dld-1 , dlat-1 , pyk-1 , and pyk-2 RNAi further caused susceptibility to 6-PPDQ toxicity. Our results suggested 6-PPDQ exposure risk in resulting in damage on citric acid cycle, which was linked to its toxicity induction.
研究领域:
环境毒理学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
BIOPHYSICAL CHEMISTRY
·
2025
·
IF 2.2
Jing Zhang,Qiang Ma,Honghui Wang,Bin Chen,Yan Li,Yingmin Liao
The rubber antioxidant, N -(1,3-dimethylbutyl)- N ′-phenyl- p -phenylenediamine (6-PPD), as an emerging pollutant, is receiving more and more attention recently. This study investigated the intermolecular interactions of 6-PPD with two key biological macromolecules, human serum albumin (HSA) and alpha-glucosidase (AG), to understand the transport and toxic effects of 6-PPD. Using multiple spectroscopic methods and molecular docking technology, the results demonstrated that 6-PPD could bind to both HSA and AG, thereby inducing fluorescence quenching and conformational changes in both proteins. The binding constants were determined to be (5.93 ± 0.20) × 10 5 and (3.17 ± 0.15) × 10 4 L mol −1 respectively for HSA-6-PPD and AG-6-PPD systems at 298 K, revealing strong binding affinities. Molecular docking identified specific binding sites and non-covalent interactions of the two systems. MD and Energy decomposition analysis revealed the dynamics conformational changes of the complexes and identified van der Waals and electrostatic interactions as primary binding drivers for both systems, while polar solvation energy impeded complex formation. TYR161, ILE142, and TYR138 dominated HSA-6-PPD stabilization, whereas AG-6-PPD was driven by hydrophobic interactions with TRP1369 and VAL1373, with ARG1377 incurring substantial desolvation penalties. Synchronous fluorescence and circular dichroism spectroscopy indicated that 6-PPD binding did not disrupt the microenvironment of Tyr and Trp residues in HSA and AG, while induced structural alterations in HSA and AG that could affect their physiological function. In-vitro tests showed that 6-PPD inhibited AG activity in a dose-dependent manner, with an IC 50 of 8.22 ± 0.44 μmol L −1 . ADMET and PASS online tools was used to predict physicochemical properties and multiorgan toxicity. This work provided insights into the transport and molecular toxicity of 6-PPD, highlighting the adverse biological effects associated with this common rubber additive.
研究领域:
环境毒理学
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分子生物学
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药物代谢
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生物化学
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结构生物学
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生态风险评估
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
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2023
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IF 6.1
Zeying Yang,Boyong Cao,Xiaowei An,Zhongliang Yu,Wuduo Zhao,Fangcheng Su,Guoqing Guan,Yanhao Zhang,Zhengkun Xie,Baoxian Ye
The rapid and sensitive determination of antioxidant N-(1,3-dimethylbutyl)-N′-phenyl- p -henylenediamine (6-PPD) in the environment is crucial for early intervention to prevent its adverse effects. Here, a reliable electrochemical sensor based on a N–C mediated γ-Mo 2 N nanocomposite (γ-Mo 2 N@N–C) modified carbon paste electrode (CPE) was developed and applied for selective and sensitive determination of 6-PPD. Benefiting from the superior stability and faster electron diffusion coefficient , the peak current responded to 6-PPD on the sensor linearly over a concentration range from 5 × 10 −8 mol L −1 to 1.0 × 10 −5 mol L −1 with a detection limit of 1.67 × 10 −8 mol L −1 (4.48 ng mL −1 ). Moreover, the sensor maintained good anti-interference ability in the determination of 6-PPD in soil samples from different regions in Zhengzhou City. Furthermore, the density functional theory (DFT) calculations combined with kinetics analysis proved that the enhanced basicity of the γ-Mo 2 N@N–C facilitated the deprotonation of 6-PPD, with the preferred orientation facet of (200) in γ-Mo 2 N playing a vital role in inducing the dissociation of 6-PPD, thereby improving the sensor's response. Such an electrochemical sensor, with its good stability and superior sensitivity, has the potential to be applied for real-time evaluation and monitoring of environmental pollutants .
研究领域:
分析化学
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环境科学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2024
·
IF 8.1
Huilin Chen,Maomao Xie,Wenjie Li,Lipin Tan,Xiaoming Cai,Mingjing Shen,Ruibin Li
The extensive use of synthetic antioxidants, notably N-(1,3-dimethylbutyl)-N′-phenyl- p -phenylenediamine (6-PPD), in rubber-related products, particularly in tire manufacturing, has induced concerns regarding their environmental impact and potential health hazards. Despite the identification of 6-PPD and its derivative, 6-PPD quinone (6-PPDQ), in various water samples and their lethal effects on certain aquatic species ( e.g. , coho salmon, rainbow trout and brook trout), the levels of airborne 6-PPD/6-PPDQ and their respiratory toxicity remain relatively unexplored. In this study, we aimed to evaluate the respiratory toxicity potential of 6-PPD and its derivatives, with a specific focus on detecting these compounds in airborne particulates and assessing their toxic effects on lung cells. Characterization of four airborne fine particulate (FP) samples revealed spherical morphologies with diameters ranging from 17.7 to 225.7 nm, displaying slight agglomeration and negative surface charge. methanol/acetonitrile extraction followed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis confirmed the presence of both 6-PPD and 6-PPDQ on the surfaces of FPs, with significant variations (0.26–1.05 μg g −1 ) in loading capacity observed among the samples. Subsequent exposure of lung cells (THP-1, BEAS-2B, and A549) to 6-PPD and 6-PPDQ revealed dose-dependent declines in mitochondrial metabolic activity induced by 6-PPD, along with severe membrane damage, ATP depletion, and pro-inflammatory cytokine release. Conversely, 6-PPDQ exhibited negligible toxicity in all tested parameters. These findings underscore the potential health risks associated with airborne 6-PPD exposure and emphasize the importance of further research into the respiratory toxicity of 6-PPD derivatives.
研究领域:
环境科学
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毒理学
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公共卫生
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2022
·
IF 10.753
Xin Hua,Xiao Feng,Geyu Liang,Jie Chao,Dayong Wang
2-((4-Methylpentan-2-yl)amino)-5-(phenylamino)cyclohexa-2,5-diene-1,4-dione (6-PPDQ) is the ozonation product of 6-PPD, a commonly used tire preservative. Although the 6-PPDQ has been frequently detected in different environmental ecosystems, its long-term effects on organisms remain still largely unknown. We here used Caenorhabditis elegans as an experimental animal to investigate the toxic effect of prolonged exposure to 6-PPDQ (0.1–100 μg/L). After the exposure, we found that 100 μg/L 6-PPDQ caused the lethality . We further selected concentrations of 0.1–10 μg/L to examine the possible intestinal toxicity induced by 6-PPDQ. Although 0.1–10 μg/L 6-PPDQ could not influence intestinal morphology, the intestinal permeability was significantly enhanced by 1–10 μg/L 6-PPDQ as indicated by erioglaucine disodium staining. In addition, the expression of intestinal fatty acid transporter ACS-22 governing functional state of intestinal barrier was decreased by exposure to 1–10 μg/L 6-PPDQ. Meanwhile, intestinal reactive oxygen species (ROS) production was induced by 0.1–10 μg/L 6-PPDQ and lipofuscin accumulation reflected by intestinal autofluorescence was activated by 1–10 μg/L 6-PPDQ. Accompanied with activation of intestinal oxidative stress , expressions of some anti-oxidation related genes ( ctl-2 , sod-2 , sod-3 , and sod-4 ) were significantly increased by 0.1–10 μg/L 6-PPDQ. Moreover, intestinal RNAi of acs-22 strengthened the susceptibility of nematodes to intestinal toxicity of 6-PPDQ. Therefore, considering that the environmentally relevant concentrations of 6-PPDQ were ≤10 μg/L, our data suggested that long-term exposure to 6-PPDQ at environmentally relevant concentrations potentially results in intestinal toxicity by disrupting functional state of intestinal barrier in organisms.
研究领域:
环境毒理学
·
分子生物学
·
生物化学
✓ 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）