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
Nutrients
·
2023
·Vol. 15
·期 19
·4176
·
IF 5.9
Yuxu Chen,Zhiye Zhao,Shancheng Guo,Yaxian Li,Haiaolong Yin,Lei Tian,Guiguang Cheng,Ye Li
Alcoholic liver disease (ALD), leading to the most common chronic liver diseases, is increasingly emerging as a global health problem, which is intensifying the need to develop novel treatments. Herein, our work aimed to estimate the therapeutic efficacy of red rice (Oryza sativaL.) seed coat on ALD and further uncover the underlying mechanisms. Red rice seed coat extract (RRA) was obtained with citric acid–ethanol and analyzed via a widely targeted components approach. The potential targets of RRA to ALD were predicted by bioinformatics analysis. Drunken behavior, histopathological examination, liver function, gut microbiota composition and intestinal barrier integrity were used to assess the effects of RRA (RRAH, 600 mg/kg·body weight; RRAL, 200 mg/kg·body weight) on ALD. Oxidative stress, inflammation, apoptosis associated factors and signaling pathways were measured by corresponding kits, Western blot and immunofluorescence staining. In ALD model mice, RRA treatment increased sphingosine kinase 2 (SPHK2) and sphingosine-1-phosphate (S1P) levels, improved gut microbiota composition, restored intestinal barrier, decreased lipopolysaccharide (LPS) levels in plasma and the liver, cut down Toll-like receptor 4 (TLR4)/Nuclear factor kappa B (NF-κB) pathways, alleviated liver pathological injury and oxidative stress, attenuated inflammation and apoptosis and enhanced liver function. To sum up, RRA targeting SPHK2 can ameliorate ALD by repairing intestinal barrier damage and reducing liver LPS level via the TLR4/NF-κB pathway and intestinal microbiota, revealing that red rice seed coat holds potential as a functional food for the prevention and treatment of ALD.Keywords:red rice seed coat;alcoholic liver disease;SPHK2;gut microbiota;intestinal barrier
研究领域:
药理学
·
胃肠病学
·
微生物学
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2023
·
IF 4.7
Hairui Han,Nana He,Enzhuang Pan,Xuelian Tan,Zuwang Yang,Xueqing Li,Dahua Shi,Jingquan Dong
Avermectin (AVM) is a widely used insecticide. Due to its sensitive toxicity to aquatic organisms , the toxicology of AVM on fish intestines remains unclear. Here, we established a 96 h AVM acute toxicity model to explore the effects of AVM on the intestinal tract of carp . The 96 h LC 50 of carps exposed to AVM was 24.04 μg/L, 12.02 μg/L was selected as the high-dose group and 3.005 μg/L was selected as the low-dose group. After 96 h of exposure, intestinal tissues were collected and subsequently analyzed for histopathology, the activities of antioxidant oxidases (CAT, SOD , GSH-Px), and the expression of mRNA associated with oxidative stress , inflammation, and apoptosis. Our study showed that AVM exposure caused intestinal damage in carp, decreased the expression of the tight junction protein gene, activated oxidative stress, induced apoptosis, and induced intestinal inflammation in carp. Therefore, we demonstrated that AVM exposure compromised the integrity of the intestinal barrier in carp, activated oxidative stress, induced endogenous apoptosis, and induced intestinal inflammatory responses. These results indicate that AVM, as a drug-sensitive to aquatic organisms, has a much more complex toxic effect on the fish intestinal tract, which provides a new perspective for studying the toxicology of AVM on the fish intestinal tract.
研究领域:
水生毒理学
·
鱼类生理学
·
环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Zhiyuan Meng,Shiran Huang,Wei Sun,Sen Yan,Xiaojun Chen,Jinling Diao,Zhiqiang Zhou,Wentao Zhu
The environmental risks of prothioconazole (PTC), a popular agricultural fungicide, and its main metabolite, prothioconazole-desthio (PTCd), have attracted more and more attention recently. In this study, the adverse effects of PTC and PTCd on liver function in mice and their underlying mechanisms have been systematically studied from the perspective of gut microbiota. Combining the results of physiological, biochemical, and histopathological analysis showed that PTC and PTCd exposure could cause lipid accumulation and inflammation in the liver of mice. In addition, exposure to PTC and PTCd could also significantly affect the transcriptome of liver tissue, leading to disorders of lipid metabolism of the liver. Particularly, the abundances of bacteria in liver tissues were significantly increased with PTC and PTCd exposure. Further results show that PTC and PTCd could affect the expression of genes related to inflammation and the barrier function in colon tissue, leading to intestinal dysfunction in mice. Last but not least, the results based on 16S rRNA gene sequencing and 1H NMR metabolomics analysis showed that exposure to PTC and PTCd could cause gut microbiota imbalances and cecal content metabolic profile disorders. In short, this study found that PTC and PTCd exposure could cause liver damage in mice by changing the gut microbiota, disrupting the intestinal barrier function and promoting bacterial translocation. These results clarified the key role of gut microbiota in liver damage induced by PTC and PTCd in mice and proposed a new insight into the mechanisms of liver toxicity induced by pesticides through the dialogue of the gut–liver axis.
研究领域:
毒理学
·
环境科学
·
微生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Inflammation Research
·
2025
·
IF 4.1
Yi-Xuan Zeng,Ni-Ren Li,Bing-Ying Deng,Yu-Feng Gu,Si-Fan Lu,Yi Liu
Background Ulcerative colitis is a chronic intestinal disease linked to intestinal barrier damage, ferroptosis and dysbiosis. Coix lacryma-jobi is a natural food with food-medicine homology, whose seed-derived oil (Coix seed oil, CSO) has been shown anti-inflammatory activity in vitro. Here, the effects and mechanisms of CSO on ulcerative colitis (UC) in vivo are systematically investigated.Methods Firstly, the UC mice was replicated by 3% DSS, and assessed the efficacy of CSO by observing the fecal occult blood, colon length, DAI score and pathological histomorphological changes of colon tissues. The anti-inflammatory and barrier-protective effects of CSO were observed by AB staining and qRT-PCR. Secondly, the biological targets of CSO were obtained from TCMSP database and Swiss Target Prediction database, ferroptosis targets were downloaded from FerrDb platform, and UC-related disease targets were obtained from GEO database, and the intersection of the above three was taken to obtain “CSO-UC-Ferroptosis” intersection targets, which were analysed by GO and KEGG enrichment, GSEA analysis, and immune cell infiltration and validation. Finally, the core genes of “CSO-UC-Ferroptosis” were molecular docking with the potential active components of CSO. In order to further verify the effect of CSO on ferroptosis, the GPX4 agonist RSL-3 was used to stimulate mice in vivo, and the levels of Iron, MDA and SOD were measured, and immunohistochemistry was used to detect the effects of tight junction proteins and the “CSO-UC-Ferroptosis” core protein in mice. Besides, the effect of CSO was further evaluated by observing the intercellular junctions of the colon tissues of each group under electron microscope. In addition, 16sRNA sequencing was performed on the intestinal contents of the mice to observe the effects of CSO on the intestinal flora of UC mice.Results CSO improved physiological parameters, reduced inflammation response and intestinal barrier damage, regulated ferroptosis, and restored gut microbiota balance in UC mice. Bioinformatics results showed that G6PD, ABCC1 were core targets at the intersection of CSO, UC and ferroptosis, which also demonstrated the similar expression of the core genes in DSS-induced UC mice models in vivo.Conclusion Our findings demonstrate for the first time that CSO ameliorated UC by regulating intestinal barrier damage, ferroptosis and the gut microbiota in DSS-induced mice, suggesting that CSO as a promising candidate for UC treatment and warranting further investigation.
研究领域:
药理学
·
免疫学
·
分子生物学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2025
·
IF 2.8
Ruobing Bai,Liting Ma,Fangtong Li,Lijia Pan,Yuwen Bao,Xinze Li,Shen Wang,Hao Yue,Fei Zheng
For thousands of years, traditional Chinese medicine (TCM) has made extensive use of wild ginseng. It is thought to provide vital energy effects and to boost immunity. This study aimed to clarify the processes by which short-chain fatty acids (SCFAs) metabolites and the intestinal barrier are used by total ginsenosides wild ginseng (TWG) to modulate immunity. In this study, we analyzed and identified ginsenosides in the colon using UPLC-Q-TOF-MS E methods. In the meantime, a rat model of spleen qi deficiency (SQD) was created using reserpine, and the effects of TWG on intestinal barrier function and short-chain fatty acids in the feces of SQD-affected rats were examined. 28 ginsenosides were found in the colon during this experiment, and the main components were measured. TWG considerably increased fecal concentrations of acetic, propionic and 6 others, according to SCFAs analysis. According to serum immunological markers, TWG reduced IL-17 and IL-1β levels, increased IL-10, IL-22, and TGF-β concentrations, balanced Th17/Treg ratios, and reduced toxicants such DAO and LPS in rats with SQD. TWG improved barrier function, reduced permeability, increased tight junction protein expression, and lessened intestinal injury. A favorable correlation between intestinal barrier proteins and fatty acids was shown by correlation studies. The gut barrier and SCFAs perspectives helped to clarify the mechanism by which TWG controls immune activity. This study offers a fresh theoretical framework for TWG's future advancement and application.
研究领域:
中医药学
·
免疫学
·
胃肠病学
·
微生物组研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2024
·
IF 8.1
Chaoyue Ge,Xinyu Luo,Yujie Lv,Lianchi Wu,Zhaoying Hu,Weichen Huang,Shenao Zhan,Xinyu Shen,Cai Hui,Dongyou Yu,Bing Liu
Nonylphenol (NP) is a ubiquitous endocrine disruptor that persists in the environment and can significantly contribute to serious health hazards, particularly intestinal barrier injury. Plant essential oils (EOs) have recently gained widespread interest due to their potential for improving intestinal health. However, the precise mechanism and protective effects of EOs ameliorating the intestinal damages induced by NP exposure remain unclear. To clarify the potential mechanism and protective impact of EOs against intestinal injury induced by NP, a total of 144 one-day-old male ducks were randomly allocated to four groups: CON (basal diet), EO (basal diet + 200 mg/kg EOs), NP (basal diet + 40 mg/kg NP), and NPEO (basal diet + 200 mg/kg EOs + 40 mg/kg NP). The data revealed that NP exposure significantly damaged intestinal barrier, as evidenced by a reduction in the levels of tight junction gene expression and an increase in intestinal permeability. Additionally, it disturbed gut microbiota, as well as interfered with tryptophan (Trp) metabolism. The NP-induced disorder of Trp metabolism restrained the activation of aryl hydrocarbon receptor (AhR) and resulted in decreased the expression levels of CYP1A1 , IL-22 , and STAT3 genes, which were alleviated after treatment with EOs. Taken together, NP exposure resulted in impairment of the intestinal barrier function, disruption of gut microbiota, and disturbances in Trp metabolism. Dietary EOs supplementation alleviated the intestinal barrier injury induced by NP through the Trp/AhR/IL-22 signaling pathway.
研究领域:
环境科学
·
营养学
·
微生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Cellular and Infection Microbiology
·
2025
·
IF 4.8
Feng-Hua Xu,Xiao Sun,Jun Zhu,Ling-Yang Kong,Yuan Chang,Ning Li,Wen-Xiang Hui,Cong-Peng Zhang,Yi-Ming Cheng,Wen-Xin Han,Zhi-Min Tian,Yan-Ning Qiao,Dong-feng Chen,Lei Liu,Da-Yun Feng,Jing Han
Background Recent research has made significant progress in elucidating gastrointestinal complications following acute cerebral infarction (ACI), which includes disorders in intestinal motility and dysbiosis of the gut microbiota. Nevertheless, the role of the gut (which is acknowledged as being the largest immune organ) in the immunoreactive effects of polydopamine nanoparticles (PDA) on acute ischemic stroke remains inadequately understood. In addition to its function in nutrient absorption, the gut acts as a protective barrier against microbes. Systemic immune responses, which are triggered by the disruption of gut barrier integrity, are considered as one of the mechanisms underlying acute ischemic stroke, with the gut-brain axis (GBA) playing a pivotal role in this process. Methods In this study, we used a PDA intervention in an ACI model to investigate ACI-like behavior, intestinal barrier function, central and peripheral inflammation, and hippocampal neuron excitability, thus aiming to elucidate the mechanisms through which PDA improves ACI via the GBA. Results Our findings indicated that as ACI mice experienced dysbiosis of the gut microbiota and intestinal barrier damage, the levels of proinflammatory factors in the serum and brain significantly increased. Additionally, the activation of astrocytes in the hippocampal region and neuronal apoptosis were observed in ACI mice. Importantly, our study is the first to provide evidence demonstrating that PDA effectively suppresses the neuroimmune interactions of the gut-brain axis and significantly improves intestinal epithelial barrier integrity. Conclusion We hope that our discoveries will serve as a foundation for further explorations of the therapeutic mechanisms of PDA in ACI, particularly in elucidating the protective roles of gut microbiota and intestinal barrier function, as well as in the development of more targeted clinical interventions for ACI.
研究领域:
医学
·
神经科学
·
免疫学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2019
·
IF 3.775
Yanwen Xue,Fang Huang,Rongxue Tang,Qingsheng Fan,Bing Zhang,Zhenjiang Xu,Xiaoming Sun,Zheng Ruan
Chronic exposure to cadmium (Cd) causes remarkable damage to the liver and gastrointestinal tract. Previous studies have revealed that chlorogenic acid (CGA) could improve the intestinal barrier integrity for weaned rats. Hence, this study sought to investigate the protective effects of CGA from pure reagent and sunflower seed extract (SSE) on growth performance, antioxidant indicators, inflammatory biomarkers and intestinal barrier function in Cd treated rats. A total of 32 Sprague–Dawley female rats with similar weights were randomly allotted to four treatments: control, CdCl 2 (6 mg/kg BW), co-treatment of Cd (6 mg/kg BW) and pure CGA (50 mg/kg BW), and co-treatment of Cd (6 mg/kg BW) and SSE (50 mg/kg BW) for 14 days. The data indicated that, CGA or SSE with Cd sequestration and good antioxidative ability decreased Cd absorption and accumulation in the jejunum and increased fecal Cd levels in Cd-exposed rats. Compared with the Cd group, co-treatment with CGA or SSE also alleviated inflammation, ameliorated the villus damage, reversed the disruption of tight junctions, and recovered weight gain of rats. These results suggest that CGA or SSE can protect the intestinal barrier, which is related to the alleviation of Cd-induced oxidative stress and growth decrease.
研究领域:
毒理学
·
药理学
·
胃肠病学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
You Wu,Jiaojiao Li,Wenjiao Ding,Zheng Ruan,Li Zhang
The intestinal barrier is essential for maintaining human intestinal health. The growing number of studies has shown that both puerarin and tryptophan and its metabolites have a beneficial effect on the intestinal barrier. This study aims at the combination of puerarin and tryptophan or its metabolites for improving the intestinal barrier. In our study, 40 female Sprague–Dawley rats were randomly divided into five groups (n = 8) for a 4-week experiment and dextran sodium sulfate was used to induce an intestinal barrier injury in rats. Our results showed that puerarin combined with tryptophan or its metabolites (indole-3-propionic acid, IPA) improved the intestinal barrier by enhancing the mucus layer barrier, which was mainly achieved by increasing the number of goblet cells and promoting the secretion of MUC2. Both TRPM5 and VAMP8 promoted MUC2 secretion in goblet cells through exocytosis, but their mechanisms of action are different. In our study, we found that puerarin and tryptophan showed different effects on TRPM5 and VAMP8, respectively. Puerarin enhances the expression of TRPM5, and tryptophan inhibits the expression of TRPM5; however, puerarin and tryptophan have no significant effect on the expression of VAMP8.
研究领域:
药理学
·
胃肠病学
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2022
·
IF 7.129
Ruifen Kang,Sheng Li,Aneela Perveen,Jiakun Shen,Chunmei Li
T-2 toxin belongs to the trichothecenes group A compound, mainly produced by Fusarium fungi. It has been shown that T-2 toxin could cross the placental barrier and breast milk, thus endangering the health of offspring. The present study aimed to explore the effects of maternal T-2 toxin exposure on the integrity of the intestinal barrier and the intestinal microflora of young mice. From late pregnancy (GD 14) to lactation (LD 21), pregnant mice were given T-2 toxin daily at 0, 0.005, or 0.05 mg T-2 toxin/kg BW. Postnatal day 21 (PND21), PND28, and PND56 young mice were chosen as objects to detect the influences of maternal T-2 toxin exposure to mice on the offspring. The results showed that maternal exposure to T-2 toxin disturbed the balance of the intestinal microbial flora of the young mice. Villous adhesions and fusion of ileum were observed in T-2-treated groups. In addition, supplementation of T-2 toxin significantly decreased the gene expressions of Claudin 1 , Occludin , Tjp1 , Il10 , Il6, and Tnf in PND 21. However, in PND 28, the expressions of Tnf were significantly increased . T he expressions of Claudin 1 , Occludin , Tjp1 , Il10 , Il6 and Tnf were significantly increased after T-2 toxin treatment in PND 56. These results suggested that maternal exposure to T-2 toxin has negative influences on the intestine of young mice, which may be due to the alterations of microbial composition.
研究领域:
毒理学
·
微生物学
·
发育生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2021
·
IF 6.291
Limin Wu,Yufeng Xu,Xixi Lv,Xulu Chang,Xiao Ma,Xue Tian,Xi Shi,Xuejun Li,Xianghui Kong
Food dyes, or color additives, are often added into foods, cosmetics and beverages during processing to improve the sensory attributes of the final products. However, the toxicity of tartrazine (TZ), one of the most common azo-dyes, is still unclear, and needs to be ascertained by further study. Hence, in the present study, we aimed to evaluate the effects of TZ consumption on health by using a teleost, crucian carp ( Carassius auratus ) as the experimental fish. TZ consumption (1.4, 5.5 and 10 mg/kg bwt/day) could cause severe histopathological and cellular alterations in intestine and liver. The height of intestinal villus, thickness of intestinal muscle, and microvilli density were also affected. With the increasing of TZ concentrations, the activities of antioxidant enzymes (CAT, SOD and GSH-Px), exhibited a decreasing trend, while the contents of MDA elevated. Upregulations of pro-inflammatory cytokines ( il6 and tnfα ), anti-inflammatory cytokines ( il8, and il10 ) and other immune related genes (complement component 3 ( c3 ), lysozymes ( lyz ), β-defensin 3 ( defb3 )), were observed after TZ uptake. In addition, TZ consumption also affected the community structure of the microbiota in the intestine of crucian carp. The amount of some probiotic bacteria ( Roseomonas, Rhodococcus and Bacillus ) and the bacteria ( Bacteroides and Clostridium ), producing short chain fatty acids, were significantly reduced, and some pathogenetic microorganisms (e.g. Bdellovibrio and Shewanella ) were significantly increased after TZ uptake. In summary, the data in the present study indicate that TZ consumption, even at a low concentration, may lead to adverse effects on fish health. Therefore, in aquaculture, it is necessary to be informed about the hazardous effects of TZ, and more attentions should be focused on using natural substitutes.
研究领域:
水产养殖
·
毒理学
·
微生物学
·
鱼类健康
✓ 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）