Hepatic dysfunction induced by intestinal dysbacteriosis mainly manifests as immunologic abnormity in mice

2020 ◽  
Vol 78 (6) ◽  
Author(s):  
Xia Luo ◽  
Bo Xu ◽  
Tianqin Xiong ◽  
Yulin Su ◽  
Chang liu ◽  
...  
Keyword(s):  
Potential Role ◽  
Hepatic Dysfunction ◽  
Intestinal Flora ◽  
Intestinal Wall ◽  
Mice Model ◽  
Intestinal Microbes ◽  
Transmission Electron ◽  
Tnf Α ◽  
Intestinal Dysbacteriosis

ABSTRACT Currently, the potential role of the alterations occurring in the liver immune system and intestinal flora in liver injury remains unknown. Our study aimed to explore the impacts of intestinal microbial barrier damage induced by ceftriaxone on liver immunity. We developed the BALB/c mice model by administering ceftriaxone. The intestinal microbial barrier damage was observed by 16S rRNA, and the pathological changes of intestines and livers were detected by H&E or transmission electron microscope. The activation of immunocytes were tested by Flow Cytometry; the expression of LPS, ALT, AST, IL-6 and TNF-α were detected by Limulus Test or ELISA. Compared to the control, the intestinal microbes significantly decreased in ceftriaxone group. Additionally, the weight of cecum contents increased, the intestinal wall became thinner and the villus in the small intestine and cecum were damaged. The expression of LPS and the ratio of liver lymphocytes were significantly increased. H&E results indicated the structures of liver arose the pathologic changes. Meanwhile, the content of serum ALT, AST, IL-6 and TNF-α increased. Collectively, our study indicates that the damages of gut microbial barrier induced by ceftriaxone prompted activation of immunocytes and release of inflammatory cytokines, which may lead to chronic inflammation in liver.

scholarly journals Autophagy is activated in the ovarian tissue of polycystic ovary syndrome

Reproduction ◽  
2018 ◽  
Vol 155 (1) ◽  
pp. 85-92 ◽  
Author(s):  
Da Li ◽  
Yue You ◽  
Fang-Fang Bi ◽  
Tie-Ning Zhang ◽  
Jiao Jiao ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Potential Role ◽  
Polycystic Ovary ◽  
Ovarian Tissue ◽  
Ovary Syndrome ◽  
Cellular Processes ◽  
Transmission Electron ◽  
Wide Range ◽  
Response To Stress

The importance of autophagy in polycystic ovary syndrome (PCOS)-related metabolic disorders is increasingly being recognized, but few studies have investigated the role of autophagy in PCOS. Here, transmission electron microscopy demonstrated that autophagy was enhanced in the ovarian tissue from both humans and rats with PCOS. Consistent with this, ovarian granulosa cells from PCOS rats showed increases in the autophagy marker protein light chain 3B (LC3B), whereas levels of the autophagy substrate SQSTM1/p62 were decreased. In addition, the ratio of LC3-II/LC3-I was markedly elevated in human PCOS ovarian tissue compared with normal ovarian tissue. Real-time PCR arrays indicated that 7 and 34 autophagy-related genes were down- and up-regulated in human PCOS , Signal-Net, and regression analysis suggested that there are a wide range of interactions among these 41 genes, and a potential network based on EGFR, ERBB2, FOXO1, MAPK1, NFKB1, IGF1, TP53 and MAPK9 may be responsible for autophagy activation in PCOS. Systematic functional analysis of 41 differential autophagy-related genes indicated that these genes are highly involved in specific cellular processes such as response to stress and stimulus, and are linked to four significant pathways, including the insulin, ERBB, mTOR signaling pathways and protein processing in the endoplasmic reticulum. This study provides evidence for a potential role of autophagy disorders in PCOS in which autophagy may be an important molecular event in the pathogenesis of PCOS.

scholarly journals Liver Nodules after the Fontan Operation: Role of Magnetic Resonance Elastography

2015 ◽  
Vol 42 (4) ◽  
pp. 389-392 ◽  
Author(s):  
Joseph T. Poterucha ◽  
Sudhakar K. Venkatesh ◽  
Jennifer L. Novak ◽  
Frank Cetta
Keyword(s):  
Magnetic Resonance ◽  
Potential Role ◽  
Screening Tool ◽  
Hepatic Dysfunction ◽  
Fontan Operation ◽  
Magnetic Resonance Elastography ◽  
Liver Nodules ◽  
Diagnostic Management ◽  
Fontan Palliation

Hepatic dysfunction after the Fontan surgical palliation runs an indolent course. Moreover, there is no standard method of evaluating hepatic dysfunction. Magnetic resonance elastography has emerged as an advanced screening tool for preclinical detection of hepatic fibrosis and cirrhosis. We describe the case of a patient who had undergone Fontan palliation, and then developed liver nodules and elevated tumor markers 18 years later. Her case illustrates the challenges in diagnostic management of hepatic dysfunction and the potential role of magnetic resonance elastography in monitoring these patients.

scholarly journals Acute Hepatic Dysfunction Related to Chronic Acetaminophen Administration

2021 ◽  
Vol 26 (5) ◽  
pp. 497-501
Author(s):  
Ellen Rootring ◽  
Cheryl L. Sargel ◽  
Joseph D. Tobias
Keyword(s):  
Potential Role ◽  
Hepatic Dysfunction ◽  
Esophageal Fistula ◽  
Prevention Strategies ◽  
Surgical Interventions ◽  
Button Battery ◽  
Acute Ingestion ◽  
Chronic Ingestion

Toxicity related to acetaminophen is most encountered with the acute ingestion of large doses. However, toxicity may also result from chronic ingestion, even when recommended doses are administered over a prolonged period of time. We present the case of a 20-month-old female toddler who received therapeutic recommended doses of acetaminophen (oral or intravenous) following multiple surgical interventions for treatment of a tracheo-esophageal fistula following ingestion of a button battery. The potential role of chronic acetaminophen administration in the etiology of hepatoxicity is discussed and prevention strategies are presented.

scholarly journals 5-LIPOXYGENASE INHIBITOR (ZILEUTON) PRODUCES ANTI-DEPRESSION EFFECT IN STRESS INDUCE CRS MICE MODEL

2019 ◽  
pp. 154-162
Author(s):  
SAPTARSHI PANIGRAHI ◽  
SOMNATH SURAI ◽  
HAO HONG
Keyword(s):  
Caspase 3 ◽  
Molecular Level ◽  
Behavioral Tests ◽  
Mice Model ◽  
Lipoxygenase Inhibitor ◽  
Treatment Groups ◽  
Tnf Α ◽  
Crs Model

Objective: The experiment aimed to find out the effectiveness of Zileuton, a 5-LOX inhibitor on depressive behavior and neuroinflammation in vivo. Method: Male ICR mice (25-30g) randomly distributed Veh+Veh, CRS+Vehicle, CRS+ZIL50, and CRS+ZIL100. Zileuton was orally given in the treatment groups for 21 days after 3 weeks of stress induce CRS model. Starting from the day 1, in CRS model, mice were immobilized 8 hr/day for consecutive 21 days to induce stress. After completing the drug administration, subjected the mice for behavioral tests, and then performed histopathological & Western Blotting. Result: Stress induces CRS model guide to the significant depressive-like behavior of the mice in behavioral tests which was united by adverse changes at the cellular/molecular level responsible for regulation of inflammatory and apoptotic processes. CRS triggered Microglial over activation in the DG of the hippocampus, which was successfully inhibited by Zileuton post-treatment at the dose of 100mg/kg than 50mg/kg. Level of TNF-α, IL- 1β, nuclear NF-κB p65, Bax, and cleaved Caspase-3 was high and Bcl-2 expression was low in the stress induce CRS -treated mice which were found to be opposite in the Zileuton (100mg/kg). However, the dose of 50mg/kg less to mimic the effects as exhibited more by the 100mg/kg dose of Zileuton. Conclusion: It can be concluded that selective 5-lipoxygenase inhibitor Zileuton can efficiently inhibit the depressive-like behavior/activity in CRS-induced depressive mouse model. The study is the first to show the role of 5-lipoxygenase enzyme in and Chronic Restraint Stress (CRS)-induced mice models of stress, anxiety or depression.

scholarly journals Intestinal dysbacteriosis activates tumor-associated macrophages to promote epithelial-mesenchymal transition of colorectal cancer

2018 ◽  
Vol 24 (8) ◽  
pp. 480-489 ◽  
Author(s):  
Guangsheng Wan ◽  
Manli Xie ◽  
Hongjie Yu ◽  
Hongyu Chen
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Cell Counting ◽  
Mice Model ◽  
Mesenchymal Transition ◽  
Tnf Α ◽  
Xenograft Mice Model ◽  
Intestinal Dysbacteriosis

In this study we investigated the association between intestinal dysbacteriosis with colorectal cancer progress and the underlying molecular mechanisms. Tumor progression was evaluated using xenograft mice model. The epithelial-mesenchymal transition (EMT) markers were quantified by both real-time PCR and immunoblotting. The serum content of IL-6 and TNF-α were measured with ELISA kits. Cell proliferation was determined by the Cell Counting Kit-8. Intestinal dysbacteriosis was successfully simulated by the administration of a large dose of antibiotics and was demonstrated to promote xenograft tumor growth and induce EMT. Accordingly, the serum concentrations of cytokines IL-6 and TNF-α were significantly increased. Furthermore, the production and secretion of IL-6 and TNF-α were remarkably elevated in macrophages isolated from intestinal dysbiotic mice in comparison with the normal counterparts, and conditioned medium from these was shown to significantly stimulate EMT process in HT29 cells in vitro. Macrophage depletion completely abrogated the pro-tumor effect of intestinal dysbacteriosis. Our results suggest that intestinal dysbacteriosis stimulates macrophage activation and subsequently induces EMT process via secreted pro-inflammatory cytokines IL-6 and TNF-α.

Potential role of the NADPH oxidase NOX1 in the pathogenesis of 5-fluorouracil-induced intestinal mucositis in mice

2012 ◽  
Vol 302 (10) ◽  
pp. G1133-G1142 ◽  
Author(s):  
Masashi Yasuda ◽  
Shinichi Kato ◽  
Naoki Yamanaka ◽  
Maho Iimori ◽  
Daichi Utsumi ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Caspase 3 ◽  
Potential Role ◽  
Chemotherapeutic Agent ◽  
Wild Type ◽  
Villus Height ◽  
Tnf Α ◽  
Nadph Oxidase 1 ◽  
Intestinal Mucositis

Although NADPH oxidase 1 (NOX1) has been shown to be highly expressed in the gastrointestinal tract, the physiological and pathophysiological roles of this enzyme are not yet fully understood. In the present study, we investigated the role of NOX1 in the pathogenesis of intestinal mucositis induced by the cancer chemotherapeutic agent 5-fluorouracil (5-FU) in mice. Intestinal mucositis was induced in Nox1 knockout (Nox1KO) and littermate wild-type (WT) mice via single, daily administration of 5-FU for 5 days. In WT mice, 5-FU caused severe intestinal mucositis characterized by a shortening of villus height, a disruption of crypts, a loss of body weight, and diarrhea. In Nox1KO mice, however, the severity of mucositis was significantly reduced, particularly with respect to crypt disruption. The numbers of apoptotic caspase-3- and caspase-8-activated cells in the intestinal crypt increased 24 h after the first 5-FU administration but were overall significantly lower in Nox1KO than in WT mice. Furthermore, the 5-FU-mediated upregulation of TNF-α, IL-1β, and NOX1 and the production of reactive oxygen species were significantly attenuated in Nox1KO mice compared with that in WT mice. These findings suggest that NOX1 plays an important role in the pathogenesis of 5-FU-induced intestinal mucositis. NOX1-derived ROS production following administration of 5-FU may promote the apoptotic response through upregulation of inflammatory cytokines.

scholarly journals Serum IL-33 Levels Are Associated with Liver Damage in Patients with Chronic Hepatitis C

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Juan Wang ◽  
Pingwei Zhao ◽  
Hui Guo ◽  
Xiguang Sun ◽  
Zhenyu Jiang ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Potential Role ◽  
Chinese Patients ◽  
Interleukin 33 ◽  
Tnf Α ◽  
Ifn Γ ◽  
Pathogenic Process

Interleukin-33 (IL-33) is associated with the development of Th2 responses. This study examined the potential role of IL-33 in the pathogenic process of chronic hepatitis C (CHC) in Chinese patients. The levels of serum IL-33 and sST2 in 154 patients with CHC, 24 with spontaneously resolved HCV (SR-HCV) infection and 20 healthy controls (HC), were analyzed by ELISA. The concentrations of serum IL-2, IFN-γ, TNF-α, IL-4, IL-6, and IL-10, HCV loads, ALT, AST, and HCV-Ab were measured. We found that the levels of serum IL-33 in CHC patients were significantly higher than those of SR-HCV and HC but decreased after treatment with interferon for 12 weeks. More importantly, the levels of serum IL-33 were correlated with the concentrations of ALT and AST in CHC patients. The levels of serum sST2, as a decoy receptor of IL-33, were significantly higher in CHC and SR-CHC patients than those in HC, and there was no correlation between the levels of serum sST2 and IL-33. The concentrations of serum IFN-γ and IL-6 in CHC patients were significantly lower than those of SR-HCV. These data suggest that IL-33 may be a pathogenic factor contributing to CHC-related liver injury.

scholarly journals Acetate Downregulates the Activation of NLRP3 Inflammasomes and Attenuates Lung Injury in Neonatal Mice With Bronchopulmonary Dysplasia

2021 ◽  
Vol 8 ◽  
Author(s):  
Qian Zhang ◽  
Xiao Ran ◽  
Yu He ◽  
Qing Ai ◽  
Yuan Shi
Keyword(s):  
Lung Injury ◽  
Bronchopulmonary Dysplasia ◽  
High Throughput Sequencing ◽  
Intestinal Flora ◽  
Inflammatory Factors ◽  
Mice Model ◽  
Inflammatory Reactions ◽  
Caspase 1 ◽  
Nlrp3 Inflammasomes

Background: Bronchopulmonary dysplasia (BPD) is a common pulmonary complication in preterm infants. Acetate is a metabolite produced by the gut microbiota, and its anti-inflammatory function is well known. The role of acetate in BPD has not been studied. Here, we investigate the effects of acetate on lung inflammation and damage in mice model of BPD.Objective: To investigate the role of acetate in the development of BPD.Methods: C57BL/6 mice were randomly divided into three groups on the 3rd day after birth: room air group, hyperoxia group, and hyperoxia + acetate (250 mM, 0.02 ml/g) group. The expression of inflammatory factors was determined by ELISA and RT-PCR, and NLRP3 and caspase-1 were detected by Western blot. High-throughput sequencing was used to detect bacterial communities in the mice intestines.Results: After acetate treatment, the expression levels of TNF-α, IL-1β, IL-18, NLRP3, and caspase-1 were significantly reduced, while the expression of GPR43 was increased. In the BPD mice treated with acetate, the proportion of Escherichia-Shigella was lower than in placebo-treated BPD mice, while the abundance of Ruminococcus was increased.Conclusions: These results indicate that acetate may regulate intestinal flora and reduce inflammatory reactions and lung injury in BPD. Therefore, acetate may be an effective drug to protect against neonatal BPD.

scholarly journals Potential role of a disintegrin and metalloproteinase-17 (ADAM17) in age-associated ventricular remodeling of rats

RSC Advances ◽  
2019 ◽  
Vol 9 (25) ◽  
pp. 14321-14330 ◽  
Author(s):  
Hainiang Liu ◽  
Haoren Wang ◽  
Dong Cheng ◽  
Qinfu Wang ◽  
Zuowei Pei ◽  
...  
Keyword(s):  
Potential Role ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Myocardial Dysfunction ◽  
Left Ventricular ◽  
Tnf Α ◽  
A Disintegrin And Metalloproteinase ◽  
Factor Α ◽  
Necrosis Factor

Excessive tumor necrosis factor-α (TNF-α) could enhance cell death and aggravate left ventricular remodeling and myocardial dysfunction.

Anticryptoccal Serum Factors in Experimental Liver Disease

1968 ◽  
Vol 23 (8) ◽  
pp. 1091-1095 ◽  
Author(s):  
Hans H. Gadebusch
Keyword(s):  
Liver Disease ◽  
Host Resistance ◽  
Potential Role ◽  
Hepatic Dysfunction ◽  
Liver Necrosis ◽  
Rat Serum ◽  
Serum Factors ◽  
Glycogen Deposition ◽  
Experimental Liver

Lysozyme and β-lysin activity in rat serum have been studied biochemically and microbiologically after induction of hepatic dysfunction. Under the conditions of these experiments β-lysin activity was adversely affected by liver necrosis or cirrhosis, while both factors (β-lysin ** and lysozyme) were affected by hyperbilirubinemia. Lysozyme and β-lysin activity were unaffected in serum from rats afflicted with (a) malnutrition, (b) fatty liver in the absence of significant necrosis, (c) disturbance in porphyrin metabolism as represented by hexachlorobenzene intoxication, and (d) extent of glycogen deposition in the liver.The potential role of these and other pertinent factors in host resistance to cryptoccosis has been discussed.

Sign in / Sign up

Export Citation Format

Share Document