|
1
|
Liu M, Sheng Y, He Y, Wu S, Jin C, Shen L. Progresses in Questing for the Truth of Opioid-Related Constipation in Cancer Patients. J Cell Mol Med 2025; 29:e70553. [PMID: 40281681 PMCID: PMC12031673 DOI: 10.1111/jcmm.70553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2024] [Revised: 03/24/2025] [Accepted: 03/28/2025] [Indexed: 04/29/2025] Open
Abstract
Opioids are extensively utilised to manage pain in cancer patients, but may cause constipation which significantly impacts their prognosis and quality of life. Opioid-induced constipation (OIC) lacks effective drugs and management strategies. Opioids act on the enteric nervous system, intestinal barrier, intestinal immunity and intestinal microbiota, implying that OIC is a multifactorial process. This paper aims to examine the effects of opioids on the intestine, specifically the enteric nervous system, intestinal barrier and interstitial cells of Cajal (ICCs), and elucidate the primary mechanisms underlying OIC development and deterioration. This review suggests that enteric neurons, intestinal immunity and intestinal flora could serve as potential therapeutic targets for OIC.
Collapse
Affiliation(s)
- Mengxue Liu
- Wuxi Hospital Affiliated to Nanjing University of Chinese MedicineWuxiJiangsuChina
| | - Yedong Sheng
- Nanjing University of Chinese MedicineNanjingJiangsuChina
| | - Yingrong He
- Wuxi Hospital Affiliated to Nanjing University of Chinese MedicineWuxiJiangsuChina
| | - Shixiang Wu
- Nanjing University of Chinese MedicineNanjingJiangsuChina
| | - Chunhui Jin
- Wuxi Hospital Affiliated to Nanjing University of Chinese MedicineWuxiJiangsuChina
| | - Lijuan Shen
- Wuxi Hospital Affiliated to Nanjing University of Chinese MedicineWuxiJiangsuChina
| |
Collapse
|
|
2
|
Hazart D, Moulzir M, Delhomme B, Oheim M, Ricard C. Imaging the enteric nervous system. Front Neuroanat 2025; 19:1532900. [PMID: 40145027 PMCID: PMC11937143 DOI: 10.3389/fnana.2025.1532900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Accepted: 02/24/2025] [Indexed: 03/28/2025] Open
Abstract
The enteric nervous system (ENS) has garnered increasing scientific interest due to its pivotal role in digestive processes and its involvement in various gastrointestinal and central nervous system (CNS) disorders, including Crohn's disease, Parkinson's disease, and autism. Despite its significance, the ENS remains relatively underexplored by neurobiologists, primarily because its structure and function are less understood compared to the CNS. This review examines both pioneering methodologies that initially revealed the intricate layered structure of the ENS and recent advancements in studying its three-dimensional (3-D) organization, both in fixed samples and at a functional level, ex-vivo or in-vivo. Traditionally, imaging the ENS relied on histological techniques involving sequential tissue sectioning, staining, and microscopic imaging of single sections. However, this method has limitations representing the full complexity of the ENS's 3-D meshwork, which led to the development of more intact preparations, such as whole-mount preparation, as well as the use of volume imaging techniques. Advancements in 3-D imaging, particularly methods like spinning-disk confocal, 2-photon, and light-sheet microscopies, combined with tissue-clearing techniques, have revolutionized our understanding of the ENS's fine structure. These approaches offer detailed views of its cellular architecture, including interactions among various cell types, blood vessels, and lymphatic vessels. They have also enhanced our comprehension of ENS-related pathologies, such as inflammatory bowel disease, Hirschsprung's disease (HSCR), and the ENS's involvement in neurodegenerative disorders like Parkinson's (PD) and Alzheimer's diseases (AD). More recently, 2-photon or confocal in-vivo imaging, combined with transgenic approaches for calcium imaging, or confocal laser endomicroscopy, have opened new avenues for functional studies of the ENS. These methods enable real-time observation of enteric neuronal and glial activity and their interactions. While routinely used in CNS studies, their application to understanding local circuits and signals in the ENS is relatively recent and presents unique challenges, such as accommodating peristaltic movements. Advancements in 3-D in-vivo functional imaging are expected to significantly deepen our understanding of the ENS and its roles in gastrointestinal and neurological diseases, potentially leading to improved diagnostic and therapeutic strategies.
Collapse
Affiliation(s)
- Doriane Hazart
- Université Paris Cité, CNRS, Saints-Pères Paris Institute for the Neurosciences, Paris, France
- Doctoral School Brain, Cognition and Behaviour – ED3C - ED 158, Paris, France
| | - Marwa Moulzir
- Université Paris Cité, CNRS, Saints-Pères Paris Institute for the Neurosciences, Paris, France
| | - Brigitte Delhomme
- Université Paris Cité, CNRS, Saints-Pères Paris Institute for the Neurosciences, Paris, France
| | - Martin Oheim
- Université Paris Cité, CNRS, Saints-Pères Paris Institute for the Neurosciences, Paris, France
| | - Clément Ricard
- Université Paris Cité, CNRS, Saints-Pères Paris Institute for the Neurosciences, Paris, France
| |
Collapse
|
|
3
|
Ortiz T, Argüelles-Arias F, Illanes M, García-Montes JM, Talero E, Macías-García L, Alcudia A, Vázquez-Román V, Motilva V, De-Miguel M. Polyphenolic Maqui Extract as a Potential Nutraceutical to Treat TNBS-Induced Crohn's Disease by the Regulation of Antioxidant and Anti-Inflammatory Pathways. Nutrients 2020; 12:nu12061752. [PMID: 32545398 PMCID: PMC7353344 DOI: 10.3390/nu12061752] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 06/09/2020] [Accepted: 06/09/2020] [Indexed: 02/06/2023] Open
Abstract
Nutraceuticals include a wide variety of bioactive compounds, such as polyphenols, which have been highlighted for their remarkable health benefits. Specially, maqui berries have shown great antioxidant activity and anti-inflammatory effects on some inflammatory diseases. The objectives of the present study were to explore the therapeutic effects of maqui berries on acute-phase inflammation in Crohn’s disease. Balb/c mice were exposed to 2,4,6-trinitrobenzene sulfonic acid (TNBS) via intracolonic administration. Polyphenolic maqui extract (Ach) was administered orally daily for 4 days after TNBS induction (Curative Group), and for 7 days prior to the TNBS induction until sacrifice (Preventive Group). Our results showed that both preventive and curative Ach administration inhibited body weight loss and colon shortening, and attenuated the macroscopic and microscopic damage signs, as well as significantly reducing transmural inflammation and boosting the recovery of the mucosal architecture and its muco-secretory function. Additionally, Ach promotes macrophage polarization to the M2 phenotype and was capable of down-regulating significantly the expression of inflammatory proteins COX-2 and iNOS, and at the same time it regulates the antioxidant Nrf-2/HO-1 pathway. In conclusion, this is the first study in which it is demonstrated that the properties of Ach as could be used as a preventive and curative treatment in Crohn’s disease.
Collapse
Affiliation(s)
- Tamara Ortiz
- Department of Normal and Pathological Cytology and Histology, University of Seville, Avda. Sánchez-Pizjuán s/n, 41009 Sevilla, Spain; (M.I.); (L.M.-G.); (V.V.-R.)
- Correspondence: (T.O.); (M.D.-M.); Tel.: +34-954-551798 (T.O.); +34-955-421-025 (M.D.-M.)
| | - Federico Argüelles-Arias
- Department of Medicine, University of Seville, Avda. Sánchez-Pizjuán s/n, 41009 Sevilla, Spain; (F.A.-A.); (J.-M.G.-M.)
- Department of Gastroenterology, University Hospital Virgen Macarena, c/Dr. Fedriani, nº 3, 41009 Sevilla, Spain
| | - Matilde Illanes
- Department of Normal and Pathological Cytology and Histology, University of Seville, Avda. Sánchez-Pizjuán s/n, 41009 Sevilla, Spain; (M.I.); (L.M.-G.); (V.V.-R.)
| | - Josefa-María García-Montes
- Department of Medicine, University of Seville, Avda. Sánchez-Pizjuán s/n, 41009 Sevilla, Spain; (F.A.-A.); (J.-M.G.-M.)
| | - Elena Talero
- Department of Pharmacology, University of Seville, c/Prof García González, nº 2, 41012 Sevilla, Spain; (E.T.); (V.M.)
| | - Laura Macías-García
- Department of Normal and Pathological Cytology and Histology, University of Seville, Avda. Sánchez-Pizjuán s/n, 41009 Sevilla, Spain; (M.I.); (L.M.-G.); (V.V.-R.)
| | - Ana Alcudia
- Department of Organic and Pharmaceutical Chemistry, University of Seville, c/Prof García González, nº 2, 41012 Sevilla, Spain;
| | - Victoria Vázquez-Román
- Department of Normal and Pathological Cytology and Histology, University of Seville, Avda. Sánchez-Pizjuán s/n, 41009 Sevilla, Spain; (M.I.); (L.M.-G.); (V.V.-R.)
| | - Virginia Motilva
- Department of Pharmacology, University of Seville, c/Prof García González, nº 2, 41012 Sevilla, Spain; (E.T.); (V.M.)
| | - Manuel De-Miguel
- Department of Normal and Pathological Cytology and Histology, University of Seville, Avda. Sánchez-Pizjuán s/n, 41009 Sevilla, Spain; (M.I.); (L.M.-G.); (V.V.-R.)
- Correspondence: (T.O.); (M.D.-M.); Tel.: +34-954-551798 (T.O.); +34-955-421-025 (M.D.-M.)
| |
Collapse
|
|
4
|
Sharna SS, Balasuriya GK, Hosie S, Nithianantharajah J, Franks AE, Hill-Yardin EL. Altered Caecal Neuroimmune Interactions in the Neuroligin-3 R451C Mouse Model of Autism. Front Cell Neurosci 2020; 14:85. [PMID: 32327975 PMCID: PMC7160799 DOI: 10.3389/fncel.2020.00085] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2019] [Accepted: 03/20/2020] [Indexed: 12/12/2022] Open
Abstract
The intrinsic nervous system of the gut interacts with the gut-associated lymphoid tissue (GALT) via bidirectional neuroimmune interactions. The caecum is an understudied region of the gastrointestinal (GI) tract that houses a large supply of microbes and is involved in generating immune responses. The caecal patch is a lymphoid aggregate located within the caecum that regulates microbial content and immune responses. People with Autism Spectrum Disorder (ASD; autism) experience serious GI dysfunction, including inflammatory disorders, more frequently than the general population. Autism is a highly prevalent neurodevelopmental disorder defined by the presence of repetitive behavior or restricted interests, language impairment, and social deficits. Mutations in genes encoding synaptic adhesion proteins such as the R451C missense mutation in neuroligin-3 (NL3) are associated with autism and impair synaptic transmission. We previously reported that NL3R451C mice, a well-established model of autism, have altered enteric neurons and GI dysfunction; however, whether the autism-associated R451C mutation alters the caecal enteric nervous system and immune function is unknown. We assessed for gross anatomical changes in the caecum and quantified the proportions of caecal submucosal and myenteric neurons in wild-type and NL3R451C mice using immunofluorescence. In the caecal patch, we assessed total cellular density as well as the density and morphology of Iba-1 labeled macrophages to identify whether the R451C mutation affects neuro-immune interactions. NL3R451C mice have significantly reduced caecal weight compared to wild-type mice, irrespective of background strain. Caecal weight is also reduced in mice lacking Neuroligin-3. NL3R451C caecal ganglia contain more neurons overall and increased numbers of Nitric Oxide (NO) producing neurons (labeled by Nitric Oxide Synthase; NOS) per ganglion in both the submucosal and myenteric plexus. Overall caecal patch cell density was unchanged however NL3R451C mice have an increased density of Iba-1 labeled enteric macrophages. Macrophages in NL3R451C were smaller and more spherical in morphology. Here, we identify changes in both the nervous system and immune system caused by an autism-associated mutation in Nlgn3 encoding the postsynaptic cell adhesion protein, Neuroligin-3. These findings provide further insights into the potential modulation of neural and immune pathways.
Collapse
Affiliation(s)
- Samiha Sayed Sharna
- School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia
| | | | - Suzanne Hosie
- School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia
| | | | - Ashley E Franks
- School of Life Sciences, La Trobe University, Bundoora, VIC, Australia
| | - Elisa L Hill-Yardin
- School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia
| |
Collapse
|
|
5
|
Bochimoto H, Kondoh D, Nagata R, Ishihara Y, Tomiyasu J, Han KH, Shimada K, Sasaki M, Kitamura N, Fukushima M. Ultrastructural changes in colonic epithelial cells in a rat model of inflammatory bowel disease. Microsc Res Tech 2019; 82:1339-1344. [PMID: 31070847 DOI: 10.1002/jemt.23285] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2019] [Revised: 04/02/2019] [Accepted: 04/24/2019] [Indexed: 01/01/2023]
Abstract
Inflammatory bowel disease (IBD) is a global, chronic intractable disease. The functions of drugs and food components have been evaluated in models of IBD induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). Here, we used transmission (TEM) and osmium-maceration scanning (SEM) electron microscopy to evaluate the ultrastructure of colonic epithelial cells in rat models of IBD induced by TNBS. Histological evaluation revealed that the intestinal crypts in the most regions of the IBD-model colons were deformed and we classified them as having high cell migration rates (HMIG). The remaining regions in the intestinal crypts retained a relatively normal structure and we classified them as having low cell migration rates (LMIG). Osmium-maceration SEM revealed the mucosal fluid flowing in spaces without secretory granules in crypt goblet cells of both HMIG and LMIG regions, indicating the depletion of goblet cell mucin that is found in patients with IBD. The Golgi apparatus in absorptive cells was stacked and curled in both regions. Osmium-maceration SEM showed membrane network structures resembling endoplasmic reticulum that were large and expanded in absorptive cells with HMIG rather than with LMIG regions in IBD-model colons. These findings indicated that endoplasmic reticulum stress is associated with susceptibility to IBD and that the effects of various agents can be evaluated according to endoplasmic reticulum stress revealed by using electron microscopy in models of IBD induced by TNBS.
Collapse
Affiliation(s)
- Hiroki Bochimoto
- Division of Aerospace Medicine, Department of Cell Physiology, The Jikei University School of Medicine, Nishishinbashi 3-25-8, Minatoku, Tokyo, Japan.,Department of Life and Food Sciences, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Japan
| | - Daisuke Kondoh
- Laboratory of Veterinary Anatomy, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Japan
| | - Ryuji Nagata
- Department of Life and Food Sciences, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Japan.,The United Graduate School of Agricultural Sciences, Iwate University, Morioka, Japan
| | - Yo Ishihara
- Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Jumpei Tomiyasu
- Laboratory of Theriogenology, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Japan
| | - Kyu-Ho Han
- Department of Life and Food Sciences, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Japan
| | - Kenichiro Shimada
- Department of Life and Food Sciences, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Japan
| | - Motoki Sasaki
- Laboratory of Veterinary Anatomy, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Japan
| | - Nobuo Kitamura
- Laboratory of Veterinary Anatomy, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Japan
| | - Michihiro Fukushima
- Department of Life and Food Sciences, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Japan
| |
Collapse
|
|
6
|
Bódi N, Szalai Z, Bagyánszki M. Nitrergic Enteric Neurons in Health and Disease-Focus on Animal Models. Int J Mol Sci 2019; 20:ijms20082003. [PMID: 31022832 PMCID: PMC6515552 DOI: 10.3390/ijms20082003] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Revised: 04/17/2019] [Accepted: 04/18/2019] [Indexed: 12/14/2022] Open
Abstract
Nitrergic enteric neurons are key players of the descending inhibitory reflex of intestinal peristalsis, therefore loss or damage of these neurons can contribute to developing gastrointestinal motility disturbances suffered by patients worldwide. There is accumulating evidence that the vulnerability of nitrergic enteric neurons to neuropathy is strictly region-specific and that the two main enteric plexuses display different nitrergic neuronal damage. Alterations both in the proportion of the nitrergic subpopulation and in the total number of enteric neurons suggest that modification of the neurochemical character or neuronal death occurs in the investigated gut segments. This review aims to summarize the gastrointestinal region and/or plexus-dependent pathological changes in the number of nitric oxide synthase (NOS)-containing neurons, the NO release and the cellular and subcellular expression of different NOS isoforms. Additionally, some of the underlying mechanisms associated with the nitrergic pathway in the background of different diseases, e.g., type 1 diabetes, chronic alcoholism, intestinal inflammation or ischaemia, will be discussed.
Collapse
Affiliation(s)
- Nikolett Bódi
- Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, H-6726 Szeged, Hungary.
| | - Zita Szalai
- Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, H-6726 Szeged, Hungary.
| | - Mária Bagyánszki
- Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, H-6726 Szeged, Hungary.
| |
Collapse
|
|
7
|
The Anti-Inflammatory Role of Mannich Curcuminoids; Special Focus on Colitis. Molecules 2019; 24:molecules24081546. [PMID: 31010141 PMCID: PMC6515261 DOI: 10.3390/molecules24081546] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Revised: 04/12/2019] [Accepted: 04/17/2019] [Indexed: 01/18/2023] Open
Abstract
The incidence of inflammatory bowel disease (IBD) increases gradually in Western countries with high need for novel therapeutic interventions. Mannich curcuminoids, C142 or C150 synthetized in our laboratory, have been tested for anti-inflammatory activity in a rat model of TNBS (2,4,6-trinitrobenzenesulphonic acid) induced colitis. Treatment with C142 or C150 reduced leukocyte infiltration to the submucosa and muscular propria of the inflamed gut. C142 or C150 rescued the loss of body weight and C150 decreased the weight of standard colon preparations proportional with 20% less tissue oedema. Both C142 and C150 curcumin analogues caused 25% decrease in the severity of colonic inflammation and haemorrhagic lesion size. Colonic MPO (myeloperoxidase) enzyme activity as an indicator of intense neutrophil infiltration was 50% decreased either by C142 or C150 Mannich curcuminoids. Lipopolysaccharide (LPS) co-treatment with Mannich curcuminoids inhibited NF-κB (nuclear factor kappa B) activity on a concentration-dependent manner in an NF-κB-driven luciferase expressing reporter cell line. Co-treatment with LPS and curcuminoids, C142 or C150, resulted in NF-κB inhibition with 3.57 μM or 1.6 μM half maximal effective concentration (EC50) values, respectively. C150 exerted a profound inhibition of the expression of inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-4 (IL-4) in human PBMCs (peripheral blood mononuclear cells) upon LPS stimulus. Mannich curcuminoids reported herein possess a powerful anti-inflammatory activity.
Collapse
|
|
8
|
QI Q, WU LY, WU HG, LIU HR, WANG YY, LIU YN, WANG C, HUANG RD, WANG XM. Effect of moxibustion on the expression levels of proteins of neuron and neuropeptide in the intestinal tract of rats with Crohn's disease. WORLD JOURNAL OF ACUPUNCTURE-MOXIBUSTION 2017. [DOI: 10.1016/s1003-5257(17)30139-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
|
|
9
|
Talapka P, Berkó A, Nagy LI, Chandrakumar L, Bagyánszki M, Puskás LG, Fekete &E, Bódi N. Structural and molecular features of intestinal strictures in rats with Crohn's-like disease. World J Gastroenterol 2016; 22:5154-5164. [PMID: 27298558 PMCID: PMC4893462 DOI: 10.3748/wjg.v22.i22.5154] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2016] [Revised: 03/23/2016] [Accepted: 04/07/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To develop a new rat model we wanted to gain a better understanding of stricture formation in Crohn’s disease (CD).
METHODS: Chronic colitis was induced locally by the administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS). The relapsing inflammation characteristic to CD was mimicked by repeated TNBS treatments. Animals were randomly divided into control, once, twice and three times TNBS-treated groups. Control animals received an enema of saline. Tissue samples were taken from the strictured colonic segments and also adjacent proximally and distally to its 60, 90 or 120 d after the last TNBS or saline administrations. The frequency and macroscopic extent of the strictures were measured on digital photographs. The structural features of strictured gut wall were studied by light- and electron microscopy. Inflammation related alterations in TGF-beta 2 and 3, matrix metalloproteinases 9 (MMP9) and TIMP1 mRNA and protein expression were determined by quantitative real-time PCR and western blot analysis. The quantitative distribution of caspase 9 was determined by post-embedding immunohistochemistry.
RESULTS: Intestinal strictures first appeared 60 d after TNBS treatments and the frequency of them increased up to day 120. From day 90 an intact lamina epithelialis, reversible thickening of lamina muscularis mucosae and irreversible thickening of the muscularis externa were demonstrated in the strictured colonic segments. Nevertheless the morphological signs of apoptosis were frequently seen and excess extracellular matrix deposition was recorded between smooth muscle cells (SMCs). Enhanced caspase 9 expression on day 90 in the SMCs and on day 120 also in myenteric neurons indicated the induction of apoptosis. The mRNA expression profile of TGF-betas after repeated TNBS doses was characteristic to CD, TGF-beta 2, but not TGF-beta 3 was up-regulated. Overexpression of MMP9 and down-regulation of TIMP1 were demonstrated. The progressive increase in the amount of MMP9 protein in the strictures was also obvious between days 90 and 120 but TIMP1 protein was practically undetectable at this time.
CONCLUSION: These findings indicate that aligned structural and molecular changes in the gut wall rather than neuronal cell death play the primary role in stricture formation.
Collapse
|
|
10
|
Bagyánszki M, Bódi N. Gut region-dependent alterations of nitrergic myenteric neurons after chronic alcohol consumption. World J Gastrointest Pathophysiol 2015; 6:51-57. [PMID: 26301118 PMCID: PMC4540706 DOI: 10.4291/wjgp.v6.i3.51] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2015] [Revised: 03/27/2015] [Accepted: 06/02/2015] [Indexed: 02/06/2023] Open
Abstract
Chronic alcohol abuse damages nearly every organ in the body. The harmful effects of ethanol on the brain, the liver and the pancreas are well documented. Although chronic alcohol consumption causes serious impairments also in the gastrointestinal tract like altered motility, mucosal damage, impaired absorption of nutrients and inflammation, the effects of chronically consumed ethanol on the enteric nervous system are less detailed. While the nitrergic myenteric neurons play an essential role in the regulation of gastrointestinal peristalsis, it was hypothesised, that these neurons are the first targets of consumed ethanol or its metabolites generated in the different gastrointestinal segments. To reinforce this hypothesis the effects of ethanol on the gastrointestinal tract was investigated in different rodent models with quantitative immunohistochemistry, in vivo and in vitro motility measurements, western blot analysis, evaluation of nitric oxide synthase enzyme activity and bio-imaging of nitric oxide synthesis. These results suggest that chronic alcohol consumption did not result significant neural loss, but primarily impaired the nitrergic pathways in gut region-dependent way leading to disturbed gastrointestinal motility. The gut segment-specific differences in the effects of chronic alcohol consumption highlight the significance the ethanol-induced neuronal microenvironment involving oxidative stress and intestinal microbiota.
Collapse
|