scholarly journals GLP-2 Prevents Neuronal and Glial Changes in the Distal Colon of Mice Chronically Treated with Cisplatin

2020 ◽  
Vol 21 (22) ◽  
pp. 8875
Author(s):  
Patrizia Nardini ◽  
Alessandro Pini ◽  
Anne Bessard ◽  
Emilie Duchalais ◽  
Elena Niccolai ◽  
...  
Keyword(s):  
Nervous System ◽  
Chemotherapeutic Agent ◽  
Distal Colon ◽  
Mucosal Damage ◽  
Mucosal Inflammation ◽  
Protective Effects ◽  
Effective Strategy ◽  
Mucosal Integrity ◽  
Glial Changes ◽  
Glucagon Like Peptide

Cisplatin is a chemotherapeutic agent widely used for the treatment of solid cancers. Its administration is commonly associated with acute and chronic gastrointestinal dysfunctions, likely related to mucosal and enteric nervous system (ENS) injuries, respectively. Glucagon-like peptide-2 (GLP-2) is a pleiotropic hormone exerting trophic/reparative activities on the intestine, via antiapoptotic and pro-proliferating pathways, to guarantee mucosal integrity, energy absorption and motility. Further, it possesses anti-inflammatory properties. Presently, cisplatin acute and chronic damages and GLP-2 protective effects were investigated in the mouse distal colon using histological, immunohistochemical and biochemical techniques. The mice received cisplatin and the degradation-resistant GLP-2 analog ([Gly2]GLP-2) for 4 weeks. Cisplatin-treated mice showed mucosal damage, inflammation, IL-1β and IL-10 increase; decreased number of total neurons, ChAT- and nNOS-immunoreactive (IR) neurons; loss of SOX-10-IR cells and reduced expression of GFAP- and S100β-glial markers in the myenteric plexus. [Gly2]GLP-2 co-treatment partially prevented mucosal damage and counteracted the increase in cytokines and the loss of nNOS-IR and SOX-10-IR cells but not that of ChAT-IR neurons. Our data demonstrate that cisplatin causes mucosal injuries, neuropathy and gliopathy and that [Gly2]GLP-2 prevents these injuries, partially reducing mucosal inflammation and inducing ENS remodeling. Hence, this analog could represent an effective strategy to overcome colonic injures induced by cisplatin.

Protective effects of ethanol extract of a Mexican propolis on indomethacin-induced gastric mucosal damage in mice.

2019 ◽  
Author(s):  
DV Pilar ◽  
VVS Ibran ◽  
RC Mario ◽  
CA Octavio ◽  
MM Canales-Martinez ◽  
...  
Keyword(s):  
Ethanol Extract ◽  
Mucosal Damage ◽  
Gastric Mucosal Damage ◽  
Protective Effects

scholarly journals Gliadin Sequestration as a Novel Therapy for Celiac Disease: A Prospective Application for Polyphenols

2021 ◽  
Vol 22 (2) ◽  
pp. 595
Author(s):  
Charlene B. Van Buiten ◽  
Ryan J. Elias
Keyword(s):  
Immune Response ◽  
Celiac Disease ◽  
Gastrointestinal Symptoms ◽  
Autoimmune Disorder ◽  
Treatment Method ◽  
Mucosal Damage ◽  
Protective Effects ◽  
Novel Therapy ◽  
Gluten Proteins ◽  
Prospective Application

Celiac disease is an autoimmune disorder characterized by a heightened immune response to gluten proteins in the diet, leading to gastrointestinal symptoms and mucosal damage localized to the small intestine. Despite its prevalence, the only treatment currently available for celiac disease is complete avoidance of gluten proteins in the diet. Ongoing clinical trials have focused on targeting the immune response or gluten proteins through methods such as immunosuppression, enhanced protein degradation and protein sequestration. Recent studies suggest that polyphenols may elicit protective effects within the celiac disease milieu by disrupting the enzymatic hydrolysis of gluten proteins, sequestering gluten proteins from recognition by critical receptors in pathogenesis and exerting anti-inflammatory effects on the system as a whole. This review highlights mechanisms by which polyphenols can protect against celiac disease, takes a critical look at recent works and outlines future applications for this potential treatment method.

scholarly journals Long range synchronization within the enteric nervous system underlies propulsion along the large intestine in mice

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Nick J. Spencer ◽  
Lee Travis ◽  
Lukasz Wiklendt ◽  
Marcello Costa ◽  
Timothy J. Hibberd ◽  
...  
Keyword(s):  
Nervous System ◽  
Smooth Muscle ◽  
Enteric Nervous System ◽  
Lymphatic Vessels ◽  
Distal Colon ◽  
Distal Region ◽  
Proximal Colon ◽  
Synchronous Firing ◽  
Electrophysiological Recordings ◽  
Intrinsic Neurons

AbstractHow the Enteric Nervous System (ENS) coordinates propulsion of content along the gastrointestinal (GI)-tract has been a major unresolved issue. We reveal a mechanism that explains how ENS activity underlies propulsion of content along the colon. We used a recently developed high-resolution video imaging approach with concurrent electrophysiological recordings from smooth muscle, during fluid propulsion. Recordings showed pulsatile firing of excitatory and inhibitory neuromuscular inputs not only in proximal colon, but also distal colon, long before the propagating contraction invades the distal region. During propulsion, wavelet analysis revealed increased coherence at ~2 Hz over large distances between the proximal and distal regions. Therefore, during propulsion, synchronous firing of descending inhibitory nerve pathways over long ranges aborally acts to suppress smooth muscle from contracting, counteracting the excitatory nerve pathways over this same region of colon. This delays muscle contraction downstream, ahead of the advancing contraction. The mechanism identified is more complex than expected and vastly different from fluid propulsion along other hollow smooth muscle organs; like lymphatic vessels, portal vein, or ureters, that evolved without intrinsic neurons.

Glucagon-like Peptide-1 and the Central/Peripheral Nervous System: Crosstalk in Diabetes

2017 ◽  
Vol 28 (2) ◽  
pp. 88-103 ◽  
Author(s):  
Giovanna Muscogiuri ◽  
Ralph A. DeFronzo ◽  
Amalia Gastaldelli ◽  
Jens J. Holst
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Dichloromethane Extracts of Geranium Koreanum Kom. Alleviates Esophagus Damage in Acute Reflux Esophagitis-Induced Rats by Anti-Inflammatory Activities

2018 ◽  
Vol 19 (11) ◽  
pp. 3622 ◽  
Author(s):  
Hyeon Nam ◽  
Li Nan ◽  
Byung Choo
Keyword(s):  
Tight Junction ◽  
Reflux Esophagitis ◽  
Mucosal Damage ◽  
Enzyme Linked Immunosorbent Assay ◽  
No Production ◽  
Esophageal Mucosa ◽  
Protective Effects ◽  
Junction Protein ◽  
Inflammatory Proteins ◽  
Anti Inflammatory

Reflux esophagitis (RE) is a gastrointestinal disease caused by the reflux of gastric acid and stomach contents, and it leads to esophageal damage. Therefore, it is necessary to study the improvement of esophageal damage on a RE-induced model. The present study was accomplished to demonstrate the protective effects of a dichloromethane fraction of Geranium koreanum (DGK) plant on esophageal damage in an acute RE rat model. First, we examined the potential of anti-inflammatory effects of various fractions measured by cell cytotoxicity, morphological changes and nitric oxide (NO) production on lipopolysaccharide (LPS)-induced Raw 264.7 macrophage cells. Then, to evaluate the protective effects on RE, rats were partitioned into the following groups: normal control, RE-induced control and RE rats pre-treated with DGK 100 and 200 mg/kg body weight. The esophageal mucosal ulcer ratio was measured by the Image J program and histological changes were examined using a hematoxylin and eosin staining of the esophageal mucosa. The expression of pro-inflammatory proteins, cytokines and tight junction proteins involved in the esophageal mucosal damage were investigated using Western blotting and an enzyme-linked immunosorbent assay (ELISA) kit with esophagus tissue. DGK chemical profile and phenolic contents were analyzed by liquid chromatography-mass spectrometry (LC-MS/MS). The results showed that DGK exhibited anti-inflammatory effects against LPS-stimulated cells by significantly inhibiting NO production. Additionally, the results in vivo showed that improvement effects of DGK on esophageal mucosal damage. The expression of inflammatory proteins involved in nuclear factor κB (NF-κB) signaling pathways and tight junction protein (claudin-4 and -5) were significantly decreased in esophageal mucosa. We found the potential of DGK as source of replacement therapy products for inflammatory and RE disease.

scholarly journals Effect of pharmacologically induced smooth muscle activation on permeability in murine colitis

2003 ◽  
Vol 12 (1) ◽  
pp. 21-27 ◽  
Author(s):  
Freek J. Zijlstra ◽  
Marieke E. van Meeteren ◽  
Ingrid M. Garrelds ◽  
Maarten A.C. Meijssen
Keyword(s):  
Smooth Muscle ◽  
Intestinal Permeability ◽  
Muscle Activation ◽  
Tap Water ◽  
Water Solution ◽  
Smooth Muscles ◽  
Distal Colon ◽  
Mucosal Inflammation ◽  
Smooth Muscle Relaxation ◽  
Organ Bath

Background:Both intestinal permeability and contractility are altered in inflammatory bowel disease. Little is known about their mutual relation. Therefore, anin vitroorgan bath technique was developed to investigate the simultaneous effects of inflammation on permeability and smooth muscle contractility in different segments of the colon.Methods and materials:BALB/c mice were exposed to a 10% dextran sulphate sodium drinking water solution for 7 days to induce a mild colitis, while control mice received normal tap water. Intestinal segments were placed in an oxygenated organ bath containing Krebs buffer. Permeability was measured by the transport of the marker molecules3H-mannitol and14C-polyethyleneglycol 4000. Contractility was measured through a pressure sensor. Smooth muscle relaxation was obtained by salbutamol and l-phenylephrine, whereas contraction was achieved by carbachol and 1-(3-chlorophenyl)-biguanide.Results:The intensity of mucosal inflammation increased throughout the colon. Also, regional differences were observed in intestinal permeability. In both normal and inflamed distal colon segments, permeability was diminished compared with proximal colon segments and the non-inflamed ileum. Permeability in inflamed distal colon segments was significantly decreased compared with normal distal segments. Pharmacologically induced relaxation of smooth muscles did not affect this diminished permeability, although an increased motility positively affected permeability in inflamed and non-inflamed distal colon.Conclusions:Inflammation and permeability is inversely related. The use of pro-kinetics could counteract this disturbed permeability and, in turn, could regulate the disturbed production of inflammatory mediators.

Effect of sialoadenectomy on ethanol-induced gastric mucosal damage in the rat: role of neutrophils

1990 ◽  
Vol 68 (2) ◽  
pp. 207-210 ◽  
Author(s):  
B. L. Tepperman ◽  
B. D. Soper
Keyword(s):  
Growth Factor ◽  
Gastric Mucosa ◽  
Epidermal Growth Factor ◽  
Salivary Glands ◽  
Mucosal Damage ◽  
Gastric Mucosal Damage ◽  
Mucosal Inflammation ◽  
Prostaglandin E ◽  
Epidermal Growth ◽  
Extent Of Damage

We have observed that removal of the salivary glands is associated with an increase in the susceptibility to gastric mucosal damage in the rat. In the present study, we have examined the effect of sialoadenectomy on ethanol-induced mucosal hemorrhagic damage and myeloperoxidase (MPO) activity. Hemorrhagic damage and MPO activity in response to intragastric 50% w/v ethanol were greater in sialoadenectomized rats when compared with sham-operated animals. Pretreatment with 16,16-dimethylprostaglandin E2 (0.3 μg/kg s.c.) reduced damage and MPO activity in both sialoadenectomized and sham control rats receiving 50% ethanol. The reduction in these parameters was greater in control than in sialoadenectomized rats. Pretreatment with epidermal growth factor (5 μg/kg s.c.) significantly reduced MPO activity but did not significantly affect the extent of damage. These data suggest that sialoadenectomy is associated with an increase in mucosal inflammation in animals given ethanol. However, in some situations tissue inflammation (as indicated by MPO activity) was reduced, while the proportion of gastric mucosa exhibiting hemorrhagic damage was not changed.Key words: salivary glands, gastric mucosa, neutrophils, prostaglandin E2, epidermal growth factor.

Sign in / Sign up

Export Citation Format

Share Document