SCIENCE OF THE TOTAL ENVIRONMENT
·
2022
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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
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分子生物学
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生物化学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Mengyuan Qi,Shengjin Zhang,Hua Fang,Yunlong Yu,Junsheng Liu,Luqing Zhang
This study investigates the combined effects of polystyrene nanoplastics (PS-NPs) and deltamethrin (DEL) on mice, focusing on their different impacts among organs. Mice were exposed to PS-NPs and/or DEL for 30 days. Results showed that PS-NPs alleviated DEL-induced oxidative damage in the liver and kidney by reducing its accumulation due to decreased bioaccessibility. Conversely, PS-NPs increased DEL accumulation in the intestine, leading to enhanced susceptibility to enteric infections caused by bacteria, viruses, and parasites, as indicated by transcriptomic analysis. PS-NPs delayed DEL excretion by reducing gastrointestinal motility, as evidenced by altered neurotransmitter levels, thereby contributing to greater intestinal accumulation of DEL. Moreover, 16S rDNA sequencing revealed that PS-NPs tended to decrease beneficial bacteria and increase pathogenic bacteria in the gut microbiota, further heightening susceptibility to enteric infections upon coexposure. The findings of this study shed new light on the complex health risks associated with coexposure to nanoplastics and pesticides.
研究领域:
毒理学
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环境科学
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分子生物学
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PubMed
高影响因子
AQUATIC TOXICOLOGY
·
2025
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IF 4.3
Yuxiang Wang,Luhan Wang,Yaowen Du,Feng Yao,Miaomiao Zhao,Chenggang Cai,Ruiyu Zhu,Suqin Shao
Deoxynivalenol (DON), a prevalent mycotoxin contaminating cereal crops globally, poses significant threats to animal and human health through its gastrointestinal toxicity. While DON-induced intestinal damage has been documented in mammals, its metabolic mechanisms in aquatic species remain poorly understood, particularly in adult zebrafish models that offer unique advantages for toxicological studies. Multi-omics analysis revealed 16 key differential metabolites (9 upregulated, 7 downregulated) associated with amino acid metabolism and carbohydrate homeostasis. Pathway enrichment analysis identified significant perturbations in 2-oxocarboxylic acid metabolism and sphingolipid signaling, suggesting mitochondrial dysfunction and epithelial barrier disruption as primary toxicity mechanisms. This study establishes the first adult zebrafish model for DON intestinal toxicity evaluation, demonstrating its utility in revealing conserved metabolic targets across species. The identified pathway-specific biomarkers provide novel insights for developing dietary interventions against mycotoxin exposure.
研究领域:
毒理学
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代谢组学
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水生生物学
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PubMed
高影响因子
TOXICOLOGY
·
2025
·
IF 4.6
Liya Fang,Jinhua Xu,Chanlin Fang,Yuanxiang Jin
N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) is a commonly used rubber protectant that continuously enters the environment via groundwater. Its oxidation product, N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine quinone (6PPDQ), has garnered significant concern due to its reported toxicity in animals. This study aims to evaluate the intestinal toxicity and potential metabolic impact of 6PPD and 6PPDQ in mice following oral exposure to various doses. Our results demonstrate that both compounds compromise the intestinal barrier, as evidenced by significant increases in the expression of tight junction proteins (claudin-1 and occludin) and mucin protein (MUC2). These changes suggest an impairment of both the physical and chemical barriers of the intestine. Following exposure, there was a marked increase in pro-inflammatory cytokines (IL-6, IL-22, and NOD-1), indicating an inflammatory response associated with the disruption of lipid metabolism and macrophage polarization. Specifically, the shift from M2 to M1 macrophage polarization correlates with increased expression of M1 markers despite no change in the M1/M2 ratio over prolonged exposure. Furthermore, 6PPD exposure significantly reduced gut microbiota richness and evenness, with more pronounced changes observed in the 6PPDQ-treated group. Correlation analysis suggested that these microbial shifts may influence host carnitine and lipid metabolism pathways. Ultimately, both 6PPD and 6PPDQ exposure led to elevated levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL) in the bloodstream, attributed to decreased TC esterification. These findings highlight the potential long-term health risks associated with environmental exposure to 6PPD and 6PPDQ, particularly concerning gut integrity and metabolic dysregulation. Synopsis This study investigates the toxicity of 6PPD and its transformation product 6PPDQ, revealing their detrimental effects on intestinal health, disruption of gut microbiota, and alterations in lipid metabolism, highlighting significant implications for both environmental and human health.
研究领域:
毒理学
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环境健康
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分子生物学
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代谢学
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微生物组学
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免疫学
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药理学
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PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
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IF 5.4
Jianchao Li,Yuanjing Ma,Nuo Deng,Fei Wang,Yi Tao,Huilin Zhu,Weichen Xu,Jinjun Shan,Yongming Li,Xiao Wu
Ethnopharmacological relevance Realgar is a traditional Chinese medicine rich in arsenic, and long-term use may lead to arsenic poisoning. The toxicity of realgar has primarily focused on the liver and kidney, with limited studies on its intestinal toxicity. Niuhuang Jiedu Tablet (NHJDT) is a renowned realgar-containing formula for clearing heat and detoxifying. NHJDT compatibility significantly reduces the toxicity of realgar, but the detoxification effects and underlying mechanisms in reducing realgar-induced intestinal toxicity remain unclear. Aim of the study The study aims to investigate the detoxification mechanism of NHJDT's compatibility in reducing the intestinal toxicity of realgar. Materials and methods To evaluate the intestinal detoxification efficacy of NHJDT, mice were orally administered 0.5 % CMC-Na, realgar (0.5 and 1.0 g/kg) or NHJDT (3.9 and 7.8 g/kg) for 14 days. The intestinal detoxification effects of NHJDT were evaluated by toxic symptoms and intestinal barrier function. Changes of body weight, colon length, histopathological damage, tight junction and MUC2 proteins, and goblet cells were determined. The inflammatory factors and DAO were detected by ELISA. Further investigations including 16S rRNA sequencing, untargeted metabolomics, targeted short-chain fatty acid metabolomics and molecular docking assays were performed to explore the underlying detoxification mechanisms of NHJDT. Additionally, targeted microbiota and its derived metabolite gavage were conducted in mice to verify the detoxification effects. Results NHJDT's compatibility significantly mitigated realgar-induced intestinal toxicity and gut barrier damage. It restored gut microbiota homeostasis by modulating the abundance of Akkermansia and concurrently enhanced the transformation from tryptophan to indole-3- lactate (ILA). The supplementation with Akkermansia muciniphila ( A. muciniphila ) and its derived ILA activated the aryl hydrocarbon receptor (AhR) in mice, thereby ameliorating realgar-induced intestinal damage. Conclusion NHJDT's compatibility alleviated realgar-induced intestinal toxicity by activating the AhR pathway via A. muciniphila and ILA. This study elucidates the detoxification mechanism of NHJDT's compatibility and offers novel insights for the clinical treatment of arsenic poisoning.
研究领域:
药理学
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微生物学
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毒理学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
AQUATIC TOXICOLOGY
·
2025
·
IF 4.3
Xunyue Liu,Junyao Ge,Haojie Zhu,Peng Liu,Huidi Zhang,Qiong Rao,Wenze He,Jianqiang Sun
Spirotetramat is a novel, tetrahydrofuran-based broad-spectrum insecticide. It is widely used in global agriculture due to its high insecticidal activity. However, its long-term and extensive use causes environmental accumulation, making its toxicity to non-target organisms a key issue in environmental risk assessments. Previous studies have confirmed that it causes oxidative damage in zebrafish embryos and gonads. The toxic effects and mechanisms of spirotetramat in the zebrafish intestine remain unclear, despite its importance in digestion and absorption, immune defense, and microbiota-host interactions. This study systematically investigated the toxic effects of spirotetramat on zebrafish intestine using multidimensional approaches, including histopathological observation, detection of oxidative stress-related gene expression, and analysis of intestinal microbiota. This study found that gene expression levels of sod, cat , and gpx increased in the 0.08 mg/L group but decreased in the 2 mg/L group, indicating that low concentrations activate the intestinal antioxidant system, while high concentrations cause significant overload. Histopathological analysis revealed intestinal damage, including villus fragmentation and epithelial detachment, in the 2 mg/L treatment group. The increased alkaline phosphatase activity in the 2 mg/L group may be associated with compensatory repair. Microbiota analysis revealed an elevated quantity and diversity of intestinal flora in the treatment groups, with altered abundance of specific bacteria in the 2 mg/L treatment group. Functional prediction of the microbiota suggested that spirotetramat exposure induced changes in metabolic functions. In conclusion, spirotetramat induced intestinal oxidative stress in zebrafish, leading to intestinal barrier damage and microbiota dysbiosis. This study provides a theoretical basis for the comprehensive assessment of spirotetramat's ecological risks.
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高影响因子
ENVIRONMENTAL POLLUTION
·
2023
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IF 8.9
Mengxing Cui,Qianmei He,Ziwei Wang,Yongjiang Yu,Huan Gao,Ziqi Liu,Honghao Peng,Han Wang,Xue Zhang,Daochuan Li,Liping Chen,Xiumei Xing,Yongmei Xiao,Wen Chen,Qing Wang
Micro/nano-plastics (MPs/NPs) are a newly discovered environmental pollutant that can be ingested by humans through food and drinking water. In this study we evaluated the impact of MPs/NPs on the intestinal barrier and its mechanism. Doses of MPs/NPs were used to treat Caco-2/HT29-MTX in-vitro model and in-vivo model. In in-vitro model, 20 nm polystyrene nanoplastics (PS-NPs) had higher cytotoxicity than larger particles (200 nm and 2000 nm), and led to the increase of the permeability along with the decreased expression of tight junction proteins. Intriguingly, 20 nm PS-NPs elevated the expression of MUC2 simultaneously. Further studies revealed that PS-NPs increased the expression of HO1 through ROS generation, and then activated p38 to elevate IL-10 secretion in Caco-2 cell. The IL-10 secreted by Caco-2 cell promoted the expression of MUC2 in HT29-MTX cell through STAT1/3. Elevated MUC2 expression alleviates the cytotoxicity of PS-NPs. Besides, increased intestinal permeability and up-regulation of MUC2 through Ho1/p38/IL-10 pathway was also observed in 20 nm PS-NPs treated mouse model. In conclusion, PS-NPs can induce the intestinal toxicity and result in the increased adaptive expression of MUC2 to resist this adverse effect. People with inadequate mucin expression need to pay more attention to the toxicity of PS-NPs. This study provided a valuable insight for clarifying the mechanism and potential risk of intestinal toxicity induced by nanoplastics.
研究领域:
环境科学
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毒理学
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细胞生物学
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分子生物学
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PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2024
·
IF 6.2
Shunli Che,Mengting Huang,Huiying Ma,Zhicheng Wan,Jianbin Feng,Shuquan Ding,Xilei Li
Nanopolystyrene (NP) and cadmium (Cd) are ubiquitous contaminants in aquatic systems. The present study aimed to investigate the toxic effects of exposure to ambient concentrations of NP and/or Cd on the intestinal tract of the Chinese mitten crab ( Eriocheir sinensis ). Exposure to NP and/or Cd induced oxidative stress, as evidenced by a significant increase in lipid peroxide content (LPO), total antioxidant capacity (T-AOC), and peroxidase activity (POD), and significant decreases in superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities in E. sinensis . In addition, exposure to NP and/or Cd imbalanced the homeostasis of the intestinal microbiota, as demonstrated by the significantly increased abundance of Spiroplasma . Transcriptomic and metabolomic analyses were performed to investigate the mechanisms underlying intestinal toxicity. Our results showed that ferroptosis, ABC transporters, phosphotransferase system, apoptosis, and leukocyte transendothelial migration were disturbed after exposure to NP and/or Cd. In particular, Cd exposure affected mucin type O-glycan biosynthesis, purine metabolism, and neuroactive ligand-receptor interaction. Intriguingly, co-exposure to NP and Cd might mitigate intestinal toxicity by decreasing oxidative stress and affecting these pathways. Taken together, our study clearly demonstrates that exposure to NP and/or Cd at environmentally relevant concentrations causes intestinal toxicity in E. sinensis .
研究领域:
环境科学
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毒理学
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分子生物学
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PubMed
高影响因子
CURRENT MEDICINAL CHEMISTRY
·
2024
·
IF 3.5
Liu Wei,Zheng Yi-nan,Jiang Shuang,Ren Shen,Tang Shan,Zhang Jing,Wang Zi,Li Wei
Background: Based on the Maillard reaction principle of red ginseng, this
study innovatively synthesized a new amino acid derivative by combining arginine with
lactose through simulated synthesis and was separated and purified through repeated silica
gel and polyacrylamide gel (Bio-gel P-II) column chromatography.
Purpose: The work was aimed at elucidating the synthesis of a novel amino acid derivative
and investigating the intestinal protective activity of the novel amino acid derivative
and possible molecular mechanism by establishing the intestinal injury model induced
by cisplatin in mice.
Methods: The purity and molecular weight of the amino acid derivatives were determined
to be by electrospray ionization mass spectrometry (ESI-MS). Subsequently, by
establishing cisplatin (20 mg/kg)-induced intestinal injury in vivo for 10 days and IEC-6
cell model. The biochemical indexes and histopathological analysis were used to evaluate
the oxidative stress and inflammatory and pathological changes of intestinal tissue in
mice. The protein expression levels of p-Nuclear transcription factor-κB (p-NF-κB),
cleaved caspase 3/caspase 3, cleaved caspase 9/caspase-9, Bcl-2, Bax, cytochrome C,
phosphatidylinositol 3-kinase (PI3K), Protein Kinase B (Akt), p-PI3K, p-Akt were quantified
through immunofluorescence staining and western blot analysis.
Results: The new amino acid derivatives of chemical structure were identified to be 1-
(arginine-Nαgroup)-1-deoxy-4-O-(β-D-galactopyranosyl)-D-fructose, named Argininylfructosyl-
galactose (AFGA, C18H34N4O12). The results showed that pretreatment with a
single AFGA dose remarkably alleviated cisplatin-evoked intestinal oxidative stress injury,
and the levels of reactive oxygen species (ROS) were lessening in IEC-6 cells
(p<0.05, p<0.01) and could effectively reduce the secretion of TNF-α and IL-1β in
serum and the expression level of NF-κB protein in intestinal tissues (p<0.01). Meantime,
AFGA also significantly suppressed the caspase 3, caspase 9, cytochrome C and
Bax protein expression in intestinal tissue in mice (p<0.01), and regulated the PI3K/Akt
pathway (p<0.05, p<0.01). Importantly, the molecular docking results of AFGA also
suggested a better binding ability with the above-mentioned related target proteins.
Conclusion: The results clearly revealed AFGA as a potential multifunctional therapeutic
agent with a clear protective effect against cisplatin-induced intestinal injury may be
related to the PI3K/Akt signaling pathway.
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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生物化学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Ziyue Wang,Lu Li,Wenliang Li,Haiyang Yan,Yuan Yuan
As a food contaminant that can be quickly absorbed through the gastrointestinal system, furan has been shown to disrupt the intestinal flora and barrier. Investigation of the intestinal toxicity mechanism of furan is of great significance to health. We previously identified the regulatory impact of salidroside (SAL) against furan-provoked intestinal damage, and the present work further explored whether the alleviating effect of SAL against furan-caused intestinal injury was based on the intestinal flora; three models, normal, pseudo-germ-free, and fecal microbiota transplantation (FMT), were established, and the changes in intestinal morphology, barrier, and inflammation were observed. Moreover, 16S rDNA sequencing observed the variation of the fecal flora associated with inflammation and short-chain fatty acids (SCFAs). Results obtained from the LC–MS/MS suggested that SAL increased furan-inhibited SCFA levels, activated the mRNA expressions of SCFA receptors (GPR41, GPR43, and GPR109A), and inhibited the furan-activated TLR4/MyD88/NF-κB signaling. Analysis of protein–protein interaction further confirmed the aforementioned effects of SAL, which inhibited furan-induced barrier damage and intestinal inflammation.
研究领域:
药理学
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微生物学
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免疫学
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毒理学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ENVIRONMENTAL MANAGEMENT
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2025
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IF 8.4
Ke Li,Kun Wang,Tong Xu,Chencong Lyu,Xuejiao Yang,Hongjin Lin,Shiwen Xu
With the widespread application of the brominated flame retardant tetrabromobisphenol A (TBBPA), it poses a threat to human health, especially intestinal health. Quercetin (Que) is a flavonol compound with anti-inflammatory and antioxidant properties. However, whether Que can prevent TBBPA-induced intestinal toxicity remains unknown. Therefore, in this study, a TBBPA (75 μM) exposure model and a Que (0.1 μM) treatment model were established using mouse colon epithelial cells (MCEC). The p38 pathway, pyroptosis, and intestinal barrier function-related indicators were analyzed using an oxidative stress reagent kit, immunofluorescence staining, western blotting, and qRT-PCR. The results showed that TBBPA exposure dose-dependently reduced cell viability, impaired the antioxidant function of cells, promoted ROS accumulation, activated the p38 signalling pathway, induced pyroptosis, and decreased the expression levels of ZO-1, Occludin, and Claudin-1. Notably, Que treatment significantly restored the antioxidant enzyme activity in MCEC cells, reduced the ROS level, inhibited the p38 axis, alleviated MCEC cell pyroptosis, and recovered the intestinal barrier function. Further studies found that using LX-3 (a p38 activator) treatment disrupted the therapeutic effect of Que. In summary, Que can exert a protective effect by inhibiting the ROS-mediated p38 pathway, thereby alleviating the damage of TBBPA to MCEC cells.
研究领域:
毒理学
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细胞生物学
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药理学
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肠道健康
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产品关联
DOI
PubMed
高影响因子
Foods
·
2025
·Vol. 14
·期 2
·214
·
IF 5.1
Mengge Duan,Yuting Wang,Shiyu Chen,Jiawen Lu,Ruihong Dong,Qiang Yu,Jianhua Xie,Yi Chen
Bisphenol A (BPA) and diisobutyl (DIBP) phthalate are widely used as typical plasticizers in food packaging. Plasticizers can be released from polymers, migrate into food, and be ingested by humans, leading to various health problems. However, little research has investigated the combined toxicity of BPA and DIBP, particularly their intestinal toxicity. Our goal is to analyse the combined toxicity of BPA (50 mg/kg) and DIBP (500 mg/kg) on the intestines of KM mice. Additionally, we tried to find natural products that can inhibit or prevent the combined toxicity of BPA and DIBP. The results indicated that the combination of BPA and DIBP exposure resulted in a reduction of beneficial flora, an increase in D-Lac levels (136 ± 14 μmol/L), an increase in intestinal permeability, activation of the notch pathway, and a decline in intestinal stem cells (ISCs) to goblet cells, compared to single-exposure sources. Nevertheless,Rubus chingiiHu phenolic extract (RHPE) (200, 400 and 600 mg/kg) ameliorated the BPA and DIBP-induced intestinal microbiota disruption and intestinal mucosal barrier impairment by inhibiting the overactivation of the notch pathway. The results of this study highlight the potential risks to human health posed by the combination of BPA and DIBP and may help explain the potential pathways of enterotoxicity caused by combined ingestion.
研究领域:
毒理学
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胃肠病学
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微生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）