ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
·
2014
·
IF 1.862
Demei Xu,Lihua Hu,Xiaomin Xia,Jianbo Song,Lingrui Li,Erqun Song,Yang Song
Tetrachlorobenzoquinone (TCBQ) is an active metabolite of pentachlorophenol (PCP). Although PCP has been investigated extensively, there are only a few reports describing the toxicity effect of TCBQ, and no report regarding TCBQ-induced liver injury in vivo . In the current study, we aimed to examine the acute hepatic toxicity of TCBQ in the mice model. Chlorogenic acid (CGA) exhibits promising antioxidant activity in the past studies, thus, the second aim of this study was to evaluate the protective effect of CGA on TCBQ-induced liver injury. Our results indicated TCBQ-intoxication caused marked liver cell necrosis and inflammation but not apoptosis, and this damage was alleviated by CGA treatment. Meantime, TCBQ-intoxication enhanced serum ALT, AST activities, TBIL content, hepatic oxidative stress and lipid peroxidation, decreased GSH content and inhibited the activities of antioxidant enzymes. Western blot and immunohistochemical analysis showed that TCBQ marked up-regulated HO-1 and NQO1 expression. On the other hand, pretreatment of CGA reduced TCBQ-induced liver damage remarkably. Taking together, these results revealed that TCBQ has strong hepatic toxic effect, and at least a part of this effect is initiated by free radical and relieved with CGA administration.
研究领域:
毒理学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Microorganisms
·
2020
·Vol. 8
·期 2
·211
·
IF 4.152
Yehao Liu,Yuhui Li,Yuhong Xia,Kaiyong Liu,Lingling Ren,Yanli Ji
Cadmium (Cd), widely present in food and drinking water at low doses, can cause health risks. However, the mechanistic effects of long-term Cd exposure at low dose through dietary intake is poorly studied. The aim of this study is to elucidate whether the dysbiosis of gut microbiota caused by Cd at an environmental low dose can aggravate the injury of mice liver, and the possible mechanism is investigated. In order to explore the potential underlying mechanism, the analyses of the variation of gut microbiota composition, intestinal permeability, and hepatic transcriptome were conducted. Our results showed that gut microbiota was disturbed. The rise of intestinal permeability induced by the dysbiosis of gut microbiota resulted in more Cd ions accumulating in mice liver, but it could be restored partly through depleting gut microbiota by antibiotics cocktail. Transcriptomic analyses indicated that 162 genes were significantly differentially expressed including 59 up-regulated and 103 down-regulated in Cd treatment. These genes were involved in several important pathways. Our findings provide a better understanding about the health risks of cadmium in the environment.Keywords:transcriptome analyses;gut microbiota;cadmium;intestinal permeability
研究领域:
环境健康
·
微生物学
·
分子生物学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2024
·
IF 6.2
Xingyu Chen,Wenqian Sun,Yanting Song,Shangong Wu,Shouqi Xie,Wen Xiong,Chengdong Peng,Yu Peng,Zhengxiang Wang,Sovan Lek,Christer Hogstrand,Mette Sørensen,Lei Pan,Dong Liu
The impact of cadmium (Cd) toxicity on fish liver injury has received much attention in recent years. Currently, autophagy, apoptosis and endoplasmic reticulum stress were reported in Cd exposed fish liver, and if there are other mechanisms (such as ferroptosis) and relevant signaling pathways involved in fish remains unknown. An experiment was conducted to investigate Cd toxicity in Channa argus (Cantor, 1842) exposed to 0, 1.0, and 2.0 mg Cd/L of water for 96 h. Cd disrupted the structure of mitochondria in the liver. Besides, Cd induced ferroptosis by significantly increasing the level of Fe 2+ , ROS, MDA and significantly decreasing the level of Ferritin, GSH, GSH-Px, GPX4, GST and SOD ( p < 0.05 in all cases). In addition, the mRNA expression of ferroptosis related genes, gpx4 and slc7a11 , were significantly downregulated by Cd. Moreover, Cd exposure significantly inhibited the Nrf2/Keap1 signaling pathway, one of the pathways involved in ferroptosis, by upregulating the mRNA levels of keap1a and keap1b , and downregulating the mRNA levels of nrf2 and its target genes ( ho-1 , nqo1 and cat ). Cd exposure also caused extensive accumulation of vacuoles and lipid droplets in liver, as well as an increase in triglyceride content. Cd significantly affected lipid metabolism related enzyme activity and gene expression, which were also regulated by Nrf2/Keap1 signaling pathway. In summary, these results indicate that ferroptosis is a mechanism in waterborne Cd exposed fish liver injury via the Nrf2/Keap1 signaling pathway and the Cd induced hepatic steatosis is also modulated by Nrf2/Keap1 pathway at the whole-body level in fish. These findings provide new insights into the fish liver injury and molecular basis of Cd toxicity.
研究领域:
环境毒理学
·
鱼类生理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
·
2025
·
IF 4.9
Zhenni Liu,Ruoyun Tang,Qiurong Qi,Siting Lin,Ping Liu,Gaofeng Cai,Zhanhong Zheng,Xiaoquan Guo,Xiaona Gao
Naringenin, a flavonoid extract, possesses anti-inflammatory, antioxidant, hepatoprotective, antitumor, and antineurotoxic properties. This study investigated the anti-heat stress effects in broilers by adding 200mg/kg naringenin to the diet of Ningdu yellow chicken under heat stress conditions. Heat stress conditions was controlled at 37 ± 2°C (7:00 a.m. to 7:00 p.m.) and 24 ± 2°C (7:00 p.m. to 7:00 a.m.) at humidity maintained at 60-65%. The results suggest that naringenin elevated the body weight and the ratio of liver mass to weight of Ningdu yellow chicken significantly. Additionally, naringenin significantly reduces heat stress level, improves liver function and antioxidant capacity. Meanwhile, the levels of necroptosis indexes (CYLD, RIPK1, RIPK3 and MLKL) and oxidative stress indexes (PDC, PYGL, GLUL and GLUD1) are downregulated by naringenin. Naringenin mitigated liver damage by decreasing inflammatory indexes caused by heat stress, including NF-κB, IL-1β, IL-18 and HMGB1. This anti-inflammatory effect arose through the downlink binding of the necroptosis index (RIPK3) and the oxidative stress index (PDC) as shown in results of fluorescence co-localization and co-immunoprecipitation. The use of naringenin in poultry may be a possible feed additive to address clinical heat stress.
研究领域:
动物科学
·
分子生物学
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2021
·
IF 7.963
Xinying Wang,Ming Gao,Zihan Wang,Weiqi Cui,Jingxian Zhang,Weijie Zhang,Yu Xia,Bo Wei,Youcai Tang,Xia Xu
Bisphenol A (BPA) is widely used to manufacture packaging materials for various daily necessities and causes harmful effects in organs, especially liver injury, by generating oxidative stress. Oridonin, an active diterpenoid isolated from Rabdosia rubescens (Hemsl.) Hara , has been reported to possess a wide range of pharmacological activities including anti-inflammatory, antioxidative and antiapoptotic effects. However, the role of oridonin in BPA--induced liver injury and its potential protective mechanism have not been well characterized. In this research, we explored the metabolic alterations in the liver tissue of rats after exposure to BPA with or without pretreatment with oridonin for 14 days by metabolomics analysis based on UPLC-MS/MS. Rats were randomly divided into groups as follows: Control, Vehicle, Oridonin (10 mg/kg), Bisphenol A (500 mg/kg), bisphenol A + Oridonin (500 + 10 mg/kg), Bisphenol A + Diammonium glycyrrhizinate (500 + 40 mg/kg). The biochemical results showed that oridonin significantly reduced the levels of AST and ALT ( P < 0.05), ameliorated the abnormal histopathological changes and reduced hepatic apoptosis compared with the BPA group. Furthermore, metabolomics results revealed that purine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis and phenylalanine metabolism were reprogrammed, based on 28 identified significant differential metabolites among the Vehicle, BPA and BPA + oridonin groups. In-depth studies demonstrated that pretreatment with oridonin may play a protective role by restoring BPA-induced changes in oxidative stress and the activity of oxidase (XOD) ( P < 0.05). Additionally, oridonin could inhibit the activity of XOD by binding to it, therefore decreasing the reactive oxygen species (ROS) level, upregulating the content of hypoxanthine and xanthine, and reducing the level of uric acid in the liver ( P < 0.05). This research presents the potential protective mechanisms of oridonin on BPA-induced liver injury at the metabolic level, which might be used to identify new protective agents that prevent BPA-induced liver injury.
研究领域:
药理学
·
毒理学
·
代谢生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2024
·
IF 5.6
Xinye Shi,Yuandi Xue,Yuxin Tu,Canrong Chen,Yajing Zhang,Zian Lin,Zongwei Cai
Bile acids, a representative diagnostic indicator of liver function, are used to visualize the extent of liver injury. Numerous studies have shown that triclosan (TCS) exposure leads to abnormal bile acid metabolism. As a result, there is a requirement to develop a fast and smart means to quantitatively monitor abnormal bile acids from exposure to triclosan in bio-sample. In this work, solid-phase microextraction (SPME) probes of sea urchin-like covalent organic frameworks (COF) were in situ synthesized on steel needles by using 1,3,5-tris(4-aminophenyl)benzene (TAPB) and 2,5-dimethoxybenzene-1,4-dicarboxaldehyde (DMTP) as two organic units and employed for extraction of bile acids. This TAPB-DMTP-COF-SPME possessed an excellent specified surface area (3351 m 2 g −1 ) and a high regular porosity (∼3.6 nm), which was an ideal adsorbent to concentrate bile acids efficiently. The created probe, together with electrospray ionization mass spectrometry (ESI/MS), proved to be a fast and specific assay for the detection of bile acids in bio-samples. The proposed method had a low limitation of detection (0.03 μg L −1 ), good linearity (R 2 ≥ 0.9931), wide linear range (0.10–1000.00 μg L −1 ) and excellent enrichment factor (63.60–252.00). Based on these excellent properties, it was successful application for the analyzing of bile acids in mice liver and feces, demonstrating the great potential of TAPB-DMTP-COF-SPME-ESI/MS in bile acids detection and liver injury diagnosis.
研究领域:
分析化学
·
毒理学
·
生物医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Yao Wang,Lijing Ye,Ruikun Yan,Haibo Zhou,Guojun Zhao
Ilex asprella , a valued plant traditionally used as food and medicine, is recognized for its effect on liver protection. Polysaccharides, as the key active components in Ilex asprella (IAP), its biological activities are still unexplored. Therefore, this study investigated the preventive effects of IAP on liver injury in vivo . H&E and TUNEL staining revealed IAP could ameliorate the histomorphology changes and liver apoptosis. For antioxidant ability, IAP preconditioning released D-GalN/LPS-induced oxidative stress via Nrf2/HO-1 signaling pathway in liver, as evidenced by increasing superoxide dismutase, total antioxidant capacity, glutathione peroxidase, and inhibiting the activation of Nrf2 and HO-1. Furthermore, IAP reduced the expression of IL-6, IL-1β and TNF-α, showing good anti-inflammatory effects. According to the results from western blot, the phosphorylation of TLR4, p65, IκB, p38, ERK, and JNK were effectively inhibited with IAP pre-treatment, indicating IAP can ameliorate the liver inflammation through TLR4/NF-κB and MAPK signaling pathway. 16S RNA sequencing revealed IAP re-regulated composition of gut microbiota, including inhibiting the harmful bacteria ( Parasutterella and Erysipelatoclostridium ) enrichment and restoring the probiotics ( Lactobacillus, Dubosiella and Bacteroide ). In conclusion, this study revealed IAP can improve liver injury by inhibiting liver oxidative stress, releasing inflammation and modulating the gut microbiota.
研究领域:
药理学
·
分子生物学
·
微生物学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Kai Wang,Rui Guo,Xu-Yang Chen,Xiu-Lin Li,Zhi-Gang Hu,Xiao Wang,Chao-Yue Wang,Ya-Juan Qin,Kun Yao,Yu-Shun Yang
Hydrogen sulfide (H 2 S) performs essential functions in several physiological and pathological procedures, such as liver cirrhosis, diabetes mellitus, and cancer. To optimize the H 2 S detection in practical applications, herein, a new probe YG-H 2 S for the fluorescent imaging of H 2 S was developed. Compared with the current H 2 S probes, the main advantages of YG-H 2 S were a wide pH range (5.0–9.0), a relatively fast response (within 10 min), and high selectivity from the competitive species (including biological mercaptan). Owing to the low cytotoxicity of YG-H 2 S , it was good for the biological depth imaging in biological events. YG-H 2 S could detect endogenous H 2 S in HeLa cells. In addition, YG-H 2 S could monitor the level of H 2 S in 4 T1-xenograft and acute liver injury model mice as well as in separate tissues. Consequently, YG-H 2 S might be a potential method for detecting H 2 S in preliminary diagnosis.
研究领域:
生物化学
·
医学影像
·
病理学
✓ 已验证
DOI
高影响因子
Nutrients
·
2024
·Vol. 16
·期 10
·1468
·
IF 4.8
Yan Zhang,Hong Huang,Chuanlin Luo,Xinfeng Zhang,Yanjing Chen,Fenfang Yue,Bingqing Xie,Tingtao Chen,Changwei Zou
Cadmium (Cd) is recognized as being linked to several liver diseases. Currently, due to the limited spectrum of drugs available for the treatment of Cd intoxication, developing and designing antidotes with superior detoxification capacity and revealing their underlying mechanisms remains a major challenge. Therefore, we developed the first next-generation probioticE. coli 1917-pSK18a-MT that delivers metallothionein (MT) to overcome Cd-induced liver injury in C57BL/6 mice by utilizing bacterial surface display technology. The results demonstrate thatE. coli 1917-pSK18a-MT could efficiently express MT without altering the growth and probiotic properties of the strain. Moreover, we found thatE. coli 1917-pSK18a-MT ameliorated Cd contamination-induced hepatic steatosis, inflammatory cell infiltration, and liver fibrosis by decreasing the expression of aminotransferases along with inflammatory factors. Activation of the Nrf2-Keap1 signaling pathway also further illustrated the hepatoprotective effects of the engineered bacteria. Finally, we showed thatE. coli 1917-pSK18a-MT improved the colonic barrier function impaired by Cd induction and ameliorated intestinal flora dysbiosis in Cd-poisoned mice by increasing the relative abundance of the Verrucomicrobiota. These data revealed that the combination ofE. coli 1917and MT both alleviated Cd-induced liver injury to a greater extent and restored the integrity of colonic epithelial tissues and bacterial dysbiosis.
研究领域:
生物工程
·
毒理学
·
微生物学
✓ 已验证
DOI
高影响因子
Journal of Traditional Chinese Medicine
·
2024
·Vol. 44
·期 6
·1146
·
IF 2
Xichao XIA,Shipeng XUE,Guoying SONG,Bin LI,Huiping WANG,Ju QIU,Jihong Wang,Qingchun LIU,Yuhong MA,Jingfeng OUYANG
OBJECTIVE: To investigate the effects of Cyclocarya paliurus (C. paliurus) polysaccharide on the liver injury of diabetic rats. METHODS: Rats were divided into 6 groups, including normal group, model group, control group, low-dose group of C. paliurus polysaccharide treatment, middle-dose group of C. paliurus polysaccharide treatment and high-dose group of C. paliurus polysaccharide treatment. Histological analysis of liver was analyzed using hematoxilin and eosin. Levels of plasma biological parameters and anti-oxidative enzymes were determined by spectrophotometry. Nuclear factor kappa-B-p65 (NF-κB p65), tumor necrosis factor-α (TNF-α), interleukins 6 (IL-6), IL-1β were measured by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: Compared with that of model group, the glucose level of plasma decreased 62.32% ( P < 0.01), but glycogen and insulin level increased 1.51 times and 1.27 times in the high-dose group of C. paliurus polysaccharide treatment, respectively. Plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) level decreased 47.47% ( P < 0.05), 43.65% ( P < 0.05) and 50.51% ( P < 0.05) in the high-dose group of C. paliurus polysaccharide treatment, respectively. Superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase level increased 1.16 times ( P < 0.01), 71.28% ( P < 0.05), 1.29 times ( P < 0.01) and 87.46% ( P < 0.05) in the high-dose group of C. paliurus polysaccharide treatment, respectively. Enzyme activities of NF-κB, TNF-α, IL-1β and IL-6 were decreased 39.29% ( P < 0.05), 51.11% ( P < 0.05), 37.42% ( P < 0.05) and 36.50% ( P < 0.05), respectively. CONCLUSIONS: Administration of C. paliurus polysaccharide may play a protecting role for liver injury of diabetic rats through lowering glucose, ALT, AST, ALP level, increasing glycogen and insulin level, enhancing the anti-oxidative ability and down-regulating the inflammatory factors expression.
研究领域:
药理学
·
糖尿病学
·
肝病学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2025
·
IF 11.3
Huanxin Zhang,Yu Zhang,Shixuan Cui,Lihua Cui,Jiaxin Li,Jizhuang Chu,Yumiao Zhou,Youru Zhang,Qiang Kong
Pentachlorophenol (PCP) is widely distributed in marine environments and poses a threat to the health of marine organisms. Recent studies have demonstrated that PCP induces energy deficiency in marine organisms. However, the underlying toxification mechanism and the resulting adverse outcomes remain unclear. This study analyzed the energy metabolism of marine medaka ( Oryzias melastigma ) exposed to PCP at environmentally relevant concentrations via proteomic analysis and multiple physiological assessments. The results showed that PCP disrupted mitochondrial morphology, reduced mitochondrial membrane potential (MMP), and decreased adenosine triphosphate (ATP) levels in marine medaka. Proteomic analysis revealed that PCP induced oxidative stress, cytoskeletal disruption, and inhibition of the cytochrome bc1 complex and ATP synthase. These effects culminated in structural and functional impairments to mitochondria, which in turn inhibited ATP synthesis. Chronic PCP exposure led to enhanced glycolytic activity, the accumulation of liver lipids, and reduced liver function. The present study has deepened our understanding of the mechanism of PCP-induced energy production deficiency in marine fish and provides new insights into ecological risk assessment for PCP.
研究领域:
环境科学
·
毒理学
·
海洋生物学
✓ 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
危险品化学品经营许可证（带存储）