Differential protection by anthocyanin-rich bilberry extract and resveratrol against lipid micelle-induced oxidative stress and monolayer permeability in Caco-2 intestinal epithelial cells

2021 ◽  
Vol 12 (7) ◽  
pp. 2950-2961
Author(s):  
Maryam Ershad ◽  
Mark K. Shigenaga ◽  
Brian Bandy
Keyword(s):  
Oxidative Stress ◽  
Dietary Fat ◽  
Intestinal Epithelial Cells ◽  
Intestinal Barrier ◽  
Differential Protection ◽  
Intestinal Epithelial ◽  
Barrier Integrity ◽  
Intestinal Barrier Integrity ◽  
Monolayer Permeability ◽  
Bilberry Extract

Excess dietary fat, and associated bile acids, can impair intestinal barrier integrity, produce intestinal or systemic inflammation and promote tumorigenesis.

scholarly journals Brain-Derived Neurotrophic Factor Modulates Intestinal Barrier by Inhibiting Intestinal Epithelial Cells Apoptosis in Mice

2018 ◽  
pp. 475-485 ◽  
Author(s):  
D.-Y. ZHAO ◽  
W.-X. ZHANG ◽  
Q.-Q. QI ◽  
X. LONG ◽  
X. LI ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Colonic Mucosa ◽  
Caspase 3 ◽  
Intestinal Epithelial Cells ◽  
Intestinal Barrier ◽  
Intestinal Epithelial ◽  
Tight Junction Proteins ◽  
Intestinal Barrier Integrity ◽  
Junction Proteins ◽  
Active Caspase

We aimed to investigate the effects of brain-derived neurotrophic factor (BDNF) on apoptosis of intestinal epithelial cells (IECs) and alterations of intestinal barrier integrity using BDNF knock-out mice model. Colonic tissues from BDNF+/+ mice and BDNF+/- mice were prepared for this study. The integrity of colonic mucosa was evaluated by measuring trans-mucosa electrical resistance and tissue conductance in Ussing chamber. The colonic epithelial structure was analyzed by transmission electron microscopy. Apoptosis involvement was determined with TUNEL staining, active caspase-3 immunostaining and Western blotting for the protein expression of active caspase-3, Bax and Bcl-2. The expression levels and distribution of tight junction proteins were evaluated by immunohistochemistry or Western blots. Compared with BDNF+/+ mice, BDNF+/- mice displayed impaired integrity and ultrastructure alterations in their colonic mucosa, which was characterized by diminished microvilli, mitochondrial swelling and epithelial cells apoptosis. Altered intestinal barrier function was linked to excessive apoptosis of IECs demonstrated by the higher proportion of TUNEL-positive apoptotic cells and enhanced caspase activities in BDNF+/- mice. Increased expression of Bax and claudin-2 proteins and reduced Bcl-2 and tight junction proteins (occludin, ZO-1 and claudin-1) expression were also detected in the colonic mucosa of BDNF+/- mice. BDNF may play a role in the maintenance of intestinal barrier integrity via its anti-apoptotic properties.

scholarly journals Activation of α7nAChR Preserves Intestinal Barrier Integrity and Ameliorates Cholestasis Liver Fibrosis in Mice by Enhancing the HO-1 / STAT3 Signaling to Inhibit NF-κB Activation

2021 ◽  
Author(s):  
Wei Lei ◽  
cheng chang Zhao ◽  
sen jia Sun ◽  
ling yan Jin ◽  
jun zhi Duan
Keyword(s):  
Liver Fibrosis ◽  
Epithelial Cells ◽  
Intestinal Barrier ◽  
Therapeutic Effects ◽  
Intestinal Epithelial ◽  
Barrier Integrity ◽  
Stat3 Signaling ◽  
Stat3 Phosphorylation ◽  
Junction Protein ◽  
Intestinal Barrier Integrity

Abstract Background: Activation of alpha-7 nicotinic acetylcholine receptor (α7nAChR) can inhibit the systemic inflammatory response and preserve intestinal barrier integrity. This study aimed at elucidating the molecular mechanisms by which α7nAChR activation could inhibit intestinal barrier injury and cholestatic liver fibrosis in mice induced by bile duct ligation (BDL).Methods: The intestine-specific HO-1 knockout VillinCreHmox1-/- and control Hmox1floxp/floxp C57BL/6 mice were subjected to BDL. The therapeutic effects of GST-21, a specific ligand for α7nAChR, on systemic and intestinal inflammation, intestinal barrier integrity, liver fibrosis and injury, HO-1 expression, STAT3, AKT and NF-kBp65 activation were examined in these mice and intestinal epithelial cells co-cultured with macrophages. Results: Compared with BDL mice, α7nAChR activation by GST-21 decreased intestinal and liver injury and fibrosis in BDL mice, accompanied by reducing serum cytokine responses. In addition, activation of α7nAChR preserved the tight junction protein expression and intestinal epithelial cell barrier integrity in BDL mice and epithelial cells co-cultured with macrophages. The therapeutic effects of α7nAChR activation were mediated by enhancing HO-1 expression, STAT3 phosphorylation, and reducing the NF-kBp65 activation in intestinal tissues and epithelial cells co-cultured with macrophages. Finally, activation of α7nAChR induced HO-1 expression and STAT3 phosphorylation in an interdependent manner, independent of the PI3K/AKT signaling. Conclusion: Activation of α7nAChR enhanced HO-1 expression and STAT3 signaling to inhibit NF-κB activation, preserving the intestinal barrier integrity, and reducing inflammation and liver fibrosis in cholestasis mice. Therefore, targeting α7nAChR may be a promising interventional strategy for primary biliary cholangitis.

scholarly journals Antrodia cinnamomea Confers Obesity Resistance and Restores Intestinal Barrier Integrity in Leptin-deficient Obese Mice

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 726
Author(s):  
Yi-Ting Tsai ◽  
Jhen-Wei Ruan ◽  
Cherng-Shyang Chang ◽  
Mei-Lan Ko ◽  
Hsiu-Chuan Chou ◽  
...  
Keyword(s):  
Intestinal Barrier ◽  
Immunoblot Analysis ◽  
Intestinal Epithelial ◽  
Barrier Integrity ◽  
Antrodia Cinnamomea ◽  
Medicinal Fungus ◽  
Reduced Body ◽  
Diet Induced Obesity ◽  
Leptin Deficiency ◽  
Intestinal Barrier Integrity

Obesity is associated with metabolic disorders. Thus, obesity prevention and treatment are essential for health. Antrodia cinnamomea (AC) is a multifunctional medicinal fungus used for the treatment of various diseases and for preventing diet-induced obesity. Leptin deficiency causes over-eating and spontaneous obesity. The concomitant metabolic symptoms are more severe than diet-induced obesity. Here, we used leptin-deficient (ob/ob) mice as an animal model for over-feeding to study the effect of AC on obesity. We fed C57BL/6 mice (WT, ob+/+) and ob/ob mice with AC for four weeks before performing qRT-PCR and immunoblot analysis to elaborate AC-modulated mechanisms. Further, we used Caco-2 cells as a human intestinal epithelial barrier model to examine the effect of AC on intestinal permeability. Our results suggested that AC reduces lipid deposits of the liver and epididymal white adipose tissue (EWAT) by promoting lipid metabolism and inhibiting lipogenesis-associated genes and proteins in ob/ob mice. Moreover, AC effectively repaired intestinal-barrier injury caused by leptin deficiency and enhanced intestinal barrier integrity in Caco-2 cells. Interestingly, AC significantly reduced body weight and EWAT with no compromise on food intake in ob/ob mice. Thus, AC effectively reduced obesity caused by leptin-deficiency and can potentially be used as a nutraceutical for treating obesity.

scholarly journals Beneficial Effect of a Fermented Wheat Germ Extract in Intestinal Epithelial Cells in case of Lipopolysaccharide-Evoked Inflammation

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Z. Karancsi ◽  
A. V. Móritz ◽  
N. Lewin ◽  
A. M. Veres ◽  
Á. Jerzsele ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
Wheat Germ ◽  
Intestinal Epithelial Cells ◽  
Intestinal Barrier ◽  
Intestinal Epithelial ◽  
Wheat Germ Extract ◽  
Amplex Red ◽  
Intracellular Ros ◽  
Fermented Wheat Germ Extract

In this study, the protective effect of a fermented wheat germ extract (FWGE) against LPS-induced inflammation and oxidative stress in IPEC-J2 porcine intestinal epithelial cells was studied. Enterocytes were treated with LPS derived from Salmonella enterica ser. Typhimurium and Escherichia coli O55:B5, O111:B4, and O127:B8 strains. Intracellular ROS level and extracellular H2O2 level were followed up by two fluorescent assays (DCFH-DA and Amplex Red). The effect of FWGE on the intestinal barrier integrity was determined by transepithelial electric resistance measurements and using a FD4 fluorescent tracer dye. IL-6 concentration of supernatants was also measured by the ELISA method. Our data revealed that FWGE had a significant lowering effect on the inflammatory response especially related to oxidative stress. Treatment with FWGE (1-2%) significantly decreased the level of intracellular ROS compared to LPS-treated cells. Furthermore, LPS-triggered partial disruption of epithelial integrity was reduced after FWGE application.

scholarly journals Alkaline Reduced Water Attenuates Oxidative Stress-Induced Mitochondrial Dysfunction and Innate Immune Response Triggered by Intestinal Epithelial Dysfunction

Processes ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1828
Author(s):  
Jayson M. Antonio ◽  
Ailyn Fadriquela ◽  
Yun Ju Jeong ◽  
Cheol-Su Kim ◽  
Soo-Ki Kim
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
Mitochondrial Dysfunction ◽  
Intestinal Epithelial Cells ◽  
Intestinal Barrier ◽  
Mapk Signaling ◽  
Raw 264.7 Cells ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Reduced Water

Redox imbalance in intestinal epithelial cells is critical in the early phases of intestinal injury. Dysfunction of the intestinal barrier can result in immunological imbalance and inflammation, thus leading to intestinal syndromes and associated illnesses. Several antioxidants have been discovered to be beneficial in resolving intestinal barrier dysfunction. Of these antioxidants, the effects of alkaline reduced water (ARW) in oxidative stress of intestinal epithelial cells and its immunokine modulation in vitro is unknown. In this study, we utilized ARW-enriched media to investigate its cytoprotective effect against H2O2-induced oxidative stress in DLD1 cells. We found that ARW rescued DLD1 from oxidative stress by diluting the influence of H2O2 on oxidative stress-activated MAPK signaling and mitochondrial dysfunction. Further, intestinal oxidative stress significantly affects immunokine profiles of Raw 264.7 cells (IL-6, IL-10, MCP, TNF-a, RANTES), which can be reversed by ARW. Collectively, ARW shields intestinal epithelial cells from oxidative stress, reducing the immunological mayhem caused by barrier failure.

scholarly journals Protective Role of Natural and Semi-Synthetic Tocopherols on TNFα-Induced ROS Production and ICAM-1 and Cl-2 Expression in HT29 Intestinal Epithelial Cells

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 160
Author(s):  
Vladana Domazetovic ◽  
Irene Falsetti ◽  
Caterina Viglianisi ◽  
Kristian Vasa ◽  
Cinzia Aurilia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Properties ◽  
Intestinal Barrier ◽  
Protective Role ◽  
Intercellular Adhesion Molecule ◽  
Intestinal Epithelial ◽  
Intercellular Adhesion Molecule 1 ◽  
Beneficial Effects ◽  
Bowel Diseases

Vitamin E, a fat-soluble compound, possesses both antioxidant and non-antioxidant properties. In this study we evaluated, in intestinal HT29 cells, the role of natural tocopherols, α-Toc and δ-Toc, and two semi-synthetic derivatives, namely bis-δ-Toc sulfide (δ-Toc)2S and bis-δ-Toc disulfide (δ-Toc)2S2, on TNFα-induced oxidative stress, and intercellular adhesion molecule-1 (ICAM-1) and claudin-2 (Cl-2) expression. The role of tocopherols was compared to that of N-acetylcysteine (NAC), an antioxidant precursor of glutathione synthesis. The results show that all tocopherol containing derivatives used, prevented TNFα-induced oxidative stress and the increase of ICAM-1 and Cl-2 expression, and that (δ-Toc)2S and (δ-Toc)2S2 are more effective than δ-Toc and α-Toc. The beneficial effects demonstrated were due to tocopherol antioxidant properties, but suppression of TNFα-induced Cl-2 expression seems not only to be related with antioxidant ability. Indeed, while ICAM-1 expression is strongly related to the intracellular redox state, Cl-2 expression is TNFα-up-regulated by both redox and non-redox dependent mechanisms. Since ICAM-1 and Cl-2 increase intestinal bowel diseases, and cause excessive recruitment of immune cells and alteration of the intestinal barrier, natural and, above all, semi-synthetic tocopherols may have a potential role as a therapeutic support against intestinal chronic inflammation, in which TNFα represents an important proinflammatory mediator.

scholarly journals Chronic opioid use modulates human enteric microbiota and intestinal barrier integrity

Gut Microbes ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 1946368
Author(s):  
Angélica Cruz-Lebrón ◽  
Ramona Johnson ◽  
Claire Mazahery ◽  
Zach Troyer ◽  
Samira Joussef-Piña ◽  
...  
Keyword(s):  
Intestinal Barrier ◽  
Opioid Use ◽  
Barrier Integrity ◽  
Intestinal Barrier Integrity ◽  
Chronic Opioid Use

scholarly journals STAT3 Signalling via the IL-6ST/gp130 Cytokine Receptor Promotes Epithelial Integrity and Intestinal Barrier Function during DSS-Induced Colitis

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 187
Author(s):  
Lokman Pang ◽  
Jennifer Huynh ◽  
Mariah G. Alorro ◽  
Xia Li ◽  
Matthias Ernst ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Epithelial Integrity ◽  
Barrier Integrity ◽  
Gp130 Receptor ◽  
Stat3 Signalling

The intestinal epithelium provides a barrier against commensal and pathogenic microorganisms. Barrier dysfunction promotes chronic inflammation, which can drive the pathogenesis of inflammatory bowel disease (IBD) and colorectal cancer (CRC). Although the Signal Transducer and Activator of Transcription-3 (STAT3) is overexpressed in both intestinal epithelial cells and immune cells in IBD patients, the role of the interleukin (IL)-6 family of cytokines through the shared IL-6ST/gp130 receptor and its associated STAT3 signalling in intestinal barrier integrity is unclear. We therefore investigated the role of STAT3 in retaining epithelial barrier integrity using dextran sulfate sodium (DSS)-induced colitis in two genetically modified mouse models, to either reduce STAT1/3 activation in response to IL-6 family cytokines with a truncated gp130∆STAT allele (GP130∆STAT/+), or by inducing short hairpin-mediated knockdown of Stat3 (shStat3). Here, we show that mice with reduced STAT3 activity are highly susceptible to DSS-induced colitis. Mechanistically, the IL-6/gp130/STAT3 signalling cascade orchestrates intestinal barrier function by modulating cytokine secretion and promoting epithelial integrity to maintain a defence against bacteria. Our study also identifies a crucial role of STAT3 in controlling intestinal permeability through tight junction proteins. Thus, therapeutically targeting the IL-6/gp130/STAT3 signalling axis to promote barrier function may serve as a treatment strategy for IBD patients.

Sign in / Sign up

Export Citation Format

Share Document