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Gao Y, Guo J, Li S, Ye L, Lu B, Liu J, Luo J, Zhu Y, Chen L, Peng T, Yang J, Wang D, Xie C, Deng X, Hu B. A Bio-Adaptive Janus-Adhesive Dressing with Dynamic Lubrication Overlayer for Prevention of Postoperative Infection and Adhesion. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2500138. [PMID: 40112168 PMCID: PMC12079332 DOI: 10.1002/advs.202500138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Revised: 02/17/2025] [Indexed: 03/22/2025]
Abstract
Wound postoperative infection and adhesion are prevalent clinical conditions resulting from surgical trauma. However, integrating intraoperative repair and postoperative management into a dressing suitable for wounds with unpredictable surface shapes and surroundings remains a formidable challenge. Here, we attempt to introduce a dynamic antifouling surface as wound protective covering and report an in situ formation of slippery-adhesive Janus gel (SAJG) by assembling hydrogel (N-hydrosuccinimide ester-activated powders) and elastomer (Silicon oil-infused polydimethylsiloxane). First powders can rapidly absorb interfacial water to gel and bond to tissue based on network entanglement, forming a tough adhesive hydrogel. Then precured organosilicon is applied to hydrogel and bonded together, forming a slippery elastomer. Due to the molecular polarity difference between hydrogel and elastomer, SAJG exhibits anisotropic surface behavior as evidenced by liquid repellency (hydrophilic vs. hydrophobic), and adhesion performance (bioadhesion vs. antiadhesion). Further, in vivo models are constructed and results demonstrated that the SAJG can effectively prevent bacterial infection to promote wound healing and avoid postoperative adhesion. Predictably, the morphologically adaptive SAJG with slippery and adhesive properties will have tremendous potential in addressing complex wound infections and postoperative complications.
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Affiliation(s)
- Yuan Gao
- Department of Gastroenterology and HepatologyDigestive Endoscopy Medical Engineering Research LaboratoryWest China HospitalMed‐X Center for MaterialsSichuan UniversityChengdu610064P. R. China
| | - Junchang Guo
- Institute of Fundamental and Frontier SciencesUniversity of Electronic Science and Technology of ChinaChengdu610054P. R. China
| | - Shuangyang Li
- Institute of Fundamental and Frontier SciencesUniversity of Electronic Science and Technology of ChinaChengdu610054P. R. China
| | - Liansong Ye
- Department of Gastroenterology and HepatologyDigestive Endoscopy Medical Engineering Research LaboratoryWest China HospitalMed‐X Center for MaterialsSichuan UniversityChengdu610064P. R. China
| | - Binyang Lu
- Institute of Fundamental and Frontier SciencesUniversity of Electronic Science and Technology of ChinaChengdu610054P. R. China
| | - Jiaxin Liu
- Institute of Fundamental and Frontier SciencesUniversity of Electronic Science and Technology of ChinaChengdu610054P. R. China
| | - Jing Luo
- Institute of Fundamental and Frontier SciencesUniversity of Electronic Science and Technology of ChinaChengdu610054P. R. China
| | - Yijia Zhu
- Institute of Fundamental and Frontier SciencesUniversity of Electronic Science and Technology of ChinaChengdu610054P. R. China
| | - Liuxiang Chen
- Department of Gastroenterology and HepatologyDigestive Endoscopy Medical Engineering Research LaboratoryWest China HospitalMed‐X Center for MaterialsSichuan UniversityChengdu610064P. R. China
| | - Tingfa Peng
- Department of Gastroenterology and HepatologyDigestive Endoscopy Medical Engineering Research LaboratoryWest China HospitalMed‐X Center for MaterialsSichuan UniversityChengdu610064P. R. China
| | - Jinlong Yang
- Institute of Fundamental and Frontier SciencesUniversity of Electronic Science and Technology of ChinaChengdu610054P. R. China
| | - Dehui Wang
- Institute of Fundamental and Frontier SciencesUniversity of Electronic Science and Technology of ChinaChengdu610054P. R. China
| | - Chaoming Xie
- Key Lab of Advanced Technologies of MaterialsMinistry of EducationSchool of Materials Science and EngineeringSouthwest Jiaotong UniversityChengdu610031P. R. China
| | - Xu Deng
- Institute of Fundamental and Frontier SciencesUniversity of Electronic Science and Technology of ChinaChengdu610054P. R. China
| | - Bing Hu
- Department of Gastroenterology and HepatologyDigestive Endoscopy Medical Engineering Research LaboratoryWest China HospitalMed‐X Center for MaterialsSichuan UniversityChengdu610064P. R. China
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Cherrada N, Chemsa A, Gheraissa N, Laib I, Gueboudji Z, EL‐Shazly M, Zaater A, Abid A, Sweilam S, Emran T, Nani S, Benamor B, Ghemam Amara D, Atoki A, Messaoudi M. Gastroprotective Efficacy of North African Medicinal Plants: A Review on Their Therapeutic Potential for Peptic Ulcers. Food Sci Nutr 2024; 12:8793-8824. [PMID: 39619964 PMCID: PMC11606823 DOI: 10.1002/fsn3.4536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 09/15/2024] [Accepted: 09/29/2024] [Indexed: 01/12/2025] Open
Abstract
Peptic ulcer disease remains a prevalent gastrointestinal disorder worldwide. Current treatments often have limitations, sparking interest in alternative therapies from medicinal plants. This review examines the gastroprotective potential of 54 North African medicinal plants against peptic ulcers. An extensive literature search was conducted, focusing on plants with preclinical and clinical evidence of anti-ulcer efficacy and documented use in North African traditional medicine. The review identified several promising plant species, such as licorice (Glycyrrhiza glabra), chamomile (Matricaria chamomilla), olive (Olea europaea), pomegranate (Punica granatum), Aloe vera, and black seed (Nigella sativa), along with their bioactive constituents, including flavonoids, tannins, and terpenoids. These compounds exhibit gastroprotective properties through multiple mechanisms, such as enhancing the gastric mucosal barrier, inhibiting acid secretion, displaying antioxidant and anti-inflammatory effects, promoting ulcer healing, and combating Helicobacter pylori infection. The evidence presented includes in vitro assays, animal models, and some clinical studies. While many of the 53 plants reviewed demonstrated significant anti-ulcer effects compared to standard drugs, further clinical research is needed to establish efficacy and safety in humans. The synergistic actions of phytochemical mixtures in medicinal plant extracts likely contribute to their therapeutic potential. This review highlights the role these North African medicinal plants may play in the prevention and treatment of peptic ulcers and identifies promising candidates for further research and development of evidence-based botanical therapies.
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Affiliation(s)
- Nezar Cherrada
- Faculty of Life and Natural Sciences, Department of BiologyUniversity of El OuedEl‐OuedAlgeria
- Laboratory of Biodiversity and Application of Biotechnology in AgricultureUniversity of El OuedEl‐OuedAlgeria
| | - Ahmed Elkhalifa Chemsa
- Faculty of Life and Natural Sciences, Department of BiologyUniversity of El OuedEl‐OuedAlgeria
- Laboratory of Biodiversity and Application of Biotechnology in AgricultureUniversity of El OuedEl‐OuedAlgeria
| | - Noura Gheraissa
- Faculty of Life and Natural Sciences, Department of BiologyUniversity of El OuedEl‐OuedAlgeria
- Laboratory of Biodiversity and Application of Biotechnology in AgricultureUniversity of El OuedEl‐OuedAlgeria
| | - Ibtissam Laib
- Faculty of Life and Natural Sciences, Department of Molecular and Cellular BiologyUniversity of El OuedEl‐OuedAlgeria
| | - Zakia Gueboudji
- Faculty of Nature and Life SciencesAbbes Laghrour University of KhenchelaKhenchelaAlgeria
- Biotechnology, Water, Environment and Health LaboratoryAbbes Laghrour University of KhenchelaKhenchelaAlgeria
| | - Mohamed EL‐Shazly
- Faculty of Pharmacy, Department of PharmacognosyAin Shams UniversityCairoEgypt
| | - Abdelmalek Zaater
- Laboratory of Biodiversity and Application of Biotechnology in AgricultureUniversity of El OuedEl‐OuedAlgeria
- Faculty of Life and Natural Sciences, Department of AgronomyUniversity of El OuedEl‐OuedAlgeria
| | - Asma Abid
- Faculty of Mathematics and Matter SciencesUniversity of OuarglaOuarglaAlgeria
- Laboratory of Valorization and Promotion of Saharan Resources (VPRS)OuarglaAlgeria
| | - Sherouk Hussein Sweilam
- College of Pharmacy, Department of PharmacognosyPrince Sattam Bin Abdulaziz UniversityAl‐KharjSaudi Arabia
- Faculty of Pharmacy, Department of PharmacognosyCairo‐Suez RoadEgyptian Russian UniversityBadr City, CairoEgypt
| | - Talha Bin Emran
- Warren Alpert Medical School, Department of Pathology and Laboratory MedicineBrown UniversityProvidenceRhode IslandUSA
- Legorreta Cancer CenterBrown UniversityProvidenceRhode IslandUSA
- Faculty of Allied Health Sciences, Department of PharmacyDaffodil International UniversityDhakaBangladesh
| | - Sadok Nani
- Faculty of Life and Natural Sciences, Department of Molecular and Cellular BiologyUniversity of El OuedEl‐OuedAlgeria
| | - Bilal Benamor
- Higher School of Saharan Agriculture‐El OuedEl OuedAlgeria
- Laboratory of Genetic, Biotechnology and Valorization of Bio‐Resources (LGBVB)University of Mohamed KhiderBiskraAlgeria
| | - Djilani Ghemam Amara
- Faculty of Life and Natural Sciences, Department of BiologyUniversity of El OuedEl‐OuedAlgeria
- Laboratory Biology, Environment, and HealthUniversity of El OuedEl‐OuedAlgeria
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Aggarwal M, Lewis O, Jarrett A, Hussaini MY, Cogan NG. A Model of Gastric Mucosal pH Regulation: Extending Sensitivity Analysis Using Sobol' Indices to Understand Higher Moments. Bull Math Biol 2024; 86:77. [PMID: 38775877 PMCID: PMC11629775 DOI: 10.1007/s11538-024-01308-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Accepted: 04/25/2024] [Indexed: 06/25/2024]
Abstract
Several recent theoretical studies have indicated that a relatively simple secretion control mechanism in the epithelial cells lining the stomach may be responsible for maintaining a neutral (healthy) pH adjacent to the stomach wall, even in the face of enormous electrodiffusive acid transport from the interior of the stomach. Subsequent work used Sobol' Indices (SIs) to quantify the degree to which this secretion mechanism is "self-regulating" i.e. the degree to which the wall pH is held neutral as mathematical parameters vary. However, questions remain regarding the nature of the control that specific parameters exert over the maintenance of a healthy stomach wall pH. Studying the sensitivity of higher moments of the statistical distribution of a model output can provide useful information, for example, how one parameter may skew the distribution towards or away from a physiologically advantageous regime. In this work, we prove a relationship between SIs and the higher moments and show how it can potentially reduce the cost of computing sensitivity of said moments. We define γ -indices to quantify sensitivity of variance, skewness, and kurtosis to the choice of value of a parameter, and we propose an efficient strategy that uses both SIs and γ -indices for a more comprehensive sensitivity analysis. Our analysis uncovers a control parameter which governs the "tightness of control" that the secretion mechanism exerts on wall pH. Finally, we discuss how uncertainty in this parameter can be reduced using expert information about higher moments, and speculate about the physiological advantage conferred by this control mechanism.
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Affiliation(s)
- Manu Aggarwal
- Department of Mathematics, Florida State University, Tallahassee, USA.
| | - Owen Lewis
- Department of Mathematics & Statistics, University of New Mexico, Albuquerque, New Mexico, USA
| | - Angela Jarrett
- Institute for Computational Engineering and Sciences, University of Texas at Austin, Austin, Texas, USA
| | - M Y Hussaini
- Department of Mathematics, Florida State University, Tallahassee, USA
| | - N G Cogan
- Department of Mathematics, Florida State University, Tallahassee, USA
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Li J, Peng F, Huang H, Xu X, Guan Q, Xie M, Xiong T. Characterization, mechanism and in vivo validation of Helicobacter pylori antagonism by probiotics screened from infants' feces and oral cavity. Food Funct 2024; 15:1170-1190. [PMID: 38206113 DOI: 10.1039/d3fo04592g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2024]
Abstract
Helicobacter pylori (H. pylori) infection is a major cause of chronic gastritis, intestinal metaplasia, and gastric carcinoma. Antibiotics, the conventional regimen for eliminating H. pylori, cause severe bacterial resistance, gut dysbiosis and hepatic insufficiency. Here, fifty lactic acid bacteria (LAB) were initially screened out of 266 strains obtained from infants' feces and oral cavity. The antagonistic properties of these 50 strains against H. pylori were investigated. Based on eight metrics combined with principal component analysis, three LAB with probiotic function and excellent anti-H. pylori capacity were affirmed. Combining dynamics test, metabolite assays, adhesion assays, co-cultivation experiments, and SEM and TEM observations, LAB were found to antagonize H. pylori by causing coccoid conversion and intercellular adhesion. Furthermore, it was found that LAB antagonized H. pylori by four pathways, i.e., production of anti-H. pylori substances, inhibition of H. pylori colonization, enhancement of the gastric mucosal barrier, and anti-inflammatory effect. In addition, animal model experiments verified that the final screened superior strain L. salivarius NCUH062003 had anti-H. pylori activity in vivo. LAB also reduced IL-8 secretion, ultimately alleviating the inflammatory response of gastric mucosa. Whole genome sequencing (WGS) data showed that the NCUH062003 genome contained the secondary metabolite biosynthesis gene cluster T3PKS. Furthermore, NCUH062003 had a strong energy metabolism and substance transport capacity, and produced a small molecule heat stable peptide (SHSP, 4.1-6.5 kDa). Meanwhile, LAB proved to be safe through antibiotic susceptibility testing and CARD database comparisons.
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Affiliation(s)
- Junyi Li
- State Key Laboratory of Food Science and Resources, No. 235 Nanjing East Road, Nanchang, Jiangxi, 330047, PR China.
- School of Food Science & Technology, Nanchang University, No. 235 Nanjing East Road, Nanchang, Jiangxi, 330047, PR China
| | - Fei Peng
- State Key Laboratory of Food Science and Resources, No. 235 Nanjing East Road, Nanchang, Jiangxi, 330047, PR China.
- School of Food Science & Technology, Nanchang University, No. 235 Nanjing East Road, Nanchang, Jiangxi, 330047, PR China
| | - Hui Huang
- State Key Laboratory of Food Science and Resources, No. 235 Nanjing East Road, Nanchang, Jiangxi, 330047, PR China.
- School of Food Science & Technology, Nanchang University, No. 235 Nanjing East Road, Nanchang, Jiangxi, 330047, PR China
| | - Xiaoyan Xu
- State Key Laboratory of Food Science and Resources, No. 235 Nanjing East Road, Nanchang, Jiangxi, 330047, PR China.
- School of Food Science & Technology, Nanchang University, No. 235 Nanjing East Road, Nanchang, Jiangxi, 330047, PR China
| | - Qianqian Guan
- State Key Laboratory of Food Science and Resources, No. 235 Nanjing East Road, Nanchang, Jiangxi, 330047, PR China.
- School of Food Science & Technology, Nanchang University, No. 235 Nanjing East Road, Nanchang, Jiangxi, 330047, PR China
| | - Mingyong Xie
- State Key Laboratory of Food Science and Resources, No. 235 Nanjing East Road, Nanchang, Jiangxi, 330047, PR China.
- School of Food Science & Technology, Nanchang University, No. 235 Nanjing East Road, Nanchang, Jiangxi, 330047, PR China
| | - Tao Xiong
- State Key Laboratory of Food Science and Resources, No. 235 Nanjing East Road, Nanchang, Jiangxi, 330047, PR China.
- School of Food Science & Technology, Nanchang University, No. 235 Nanjing East Road, Nanchang, Jiangxi, 330047, PR China
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Lee M, Kim D, Kim H, Jo S, Kim OK, Lee J. Gastro-Protective Effect of Fermented Soybean ( Glycine max (L.) Merr.) in a Rat Model of Ethanol/HCl-Induced Gastric Injury. Nutrients 2022; 14:2079. [PMID: 35631223 PMCID: PMC9147855 DOI: 10.3390/nu14102079] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 05/13/2022] [Accepted: 05/13/2022] [Indexed: 11/20/2022] Open
Abstract
The present research purposed to examine the gastro-protective effect of Glycine max (L.) Merr. fermented using Lactobacillus delbrueckii ssp. delbrueckii Rosell-187 (Gastro-AD®) on ethanol/HCl-induced gastric damage, specifically on gastric acid secretion. After oral supplementation of Gastro-AD® to Sprague-Dawley (SD) rats with ethanol/HCl-induced gastric damage, we determined that Gastro-AD® attenuated the gastric mucosal lesion, hemorrhage and gastric acid secretion induced by ethanol/HCl. In addition, we observed that the Gastro-AD® treatment increased the serum prostaglandin E2 level and decreased the levels of gastric acid secretion-related receptors in both gastric tissues and primary gastric parietal cells. Furthermore, it decreased the levels of inflammatory factors, including serum histamine and expression of p-IκB, p-p65, iNOS and COX-2 and the activity of apoptotic signaling pathways, including those involving p-JNK, Bcl2/Bax, Fas, FADD, caspase-8 and caspase-3, in the stomach of the ethanol/HCl-treated rats. Thus, we suggest that Gastro-AD® supplementation may reduce ethanol/HCl-induced gastric acid secretion and prevent gastric injury.
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Affiliation(s)
- Minhee Lee
- Department of Medical Nutrition, Kyung Hee University, Yongin 17104, Korea; (M.L.); (D.K.)
| | - Dakyung Kim
- Department of Medical Nutrition, Kyung Hee University, Yongin 17104, Korea; (M.L.); (D.K.)
| | - Hyunji Kim
- Cosmax NBT, Inc., Seongnam-si 13486, Korea;
| | | | - Ok-Kyung Kim
- Division of Food and Nutrition and Human Ecology Research Institute, Chonnam National University, Gwangju 61186, Korea
| | - Jeongmin Lee
- Department of Medical Nutrition, Kyung Hee University, Yongin 17104, Korea; (M.L.); (D.K.)
- Research Institute of Clinical Nutrition, Kyung Hee University, Seoul 02447, Korea
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Oncel S, Basson MD. Gut homeostasis, injury, and healing: New therapeutic targets. World J Gastroenterol 2022; 28:1725-1750. [PMID: 35633906 PMCID: PMC9099196 DOI: 10.3748/wjg.v28.i17.1725] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 12/12/2021] [Accepted: 03/25/2022] [Indexed: 02/06/2023] Open
Abstract
The integrity of the gastrointestinal mucosa plays a crucial role in gut homeostasis, which depends upon the balance between mucosal injury by destructive factors and healing via protective factors. The persistence of noxious agents such as acid, pepsin, nonsteroidal anti-inflammatory drugs, or Helicobacter pylori breaks down the mucosal barrier and injury occurs. Depending upon the size and site of the wound, it is healed by complex and overlapping processes involving membrane resealing, cell spreading, purse-string contraction, restitution, differentiation, angiogenesis, and vasculogenesis, each modulated by extracellular regulators. Unfortunately, the gut does not always heal, leading to such pathology as peptic ulcers or inflammatory bowel disease. Currently available therapeutics such as proton pump inhibitors, histamine-2 receptor antagonists, sucralfate, 5-aminosalicylate, antibiotics, corticosteroids, and immunosuppressants all attempt to minimize or reduce injury to the gastrointestinal tract. More recent studies have focused on improving mucosal defense or directly promoting mucosal repair. Many investigations have sought to enhance mucosal defense by stimulating mucus secretion, mucosal blood flow, or tight junction function. Conversely, new attempts to directly promote mucosal repair target proteins that modulate cytoskeleton dynamics such as tubulin, talin, Ehm2, filamin-a, gelsolin, and flightless I or that proteins regulate focal adhesions dynamics such as focal adhesion kinase. This article summarizes the pathobiology of gastrointestinal mucosal healing and reviews potential new therapeutic targets.
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Affiliation(s)
- Sema Oncel
- Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, United States
| | - Marc D Basson
- Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, United States
- Department of Surgery, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, United States
- Department of Pathology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, United States
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Lewis OL, Missey E, Keener JP. Principles of slowed hydrogen diffusion through a mucus layer. Phys Rev E 2021; 104:044403. [PMID: 34781463 PMCID: PMC11542194 DOI: 10.1103/physreve.104.044403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 09/13/2021] [Indexed: 11/07/2022]
Abstract
The control of transport through mucus layers is a ubiquitous phenomenon in physiological systems. Mucus is often tasked with the mediation of passive, diffusive transport of small ionic species. However, questions remain regarding how mucin gel characteristics (charge density of the polymeric network, binding affinity of ions with mucus) govern the rate at which ions diffuse through mucus layers. Experimental studies measuring hydrogen diffusion through gastric mucus have provided conflicting results, and it is not clear if the rate of ionic diffusion through mucus layers is appreciably different than in aqueous environments (depending on experimental preparation). Here, we present a mathematical analysis of electrodiffussion of two ionic species (hydrogen and chloride) through a mucus layer. In addition to accounting for the chemical binding of hydrogen to the mucus network, we enforce a zero net current condition (as mucus layers in physiological systems are not generally electrogenic) and calculate the Donnan potential that occurs at the edge of the mucus layer. The model predicts the steady-state fluxes of ionic species and the induced potential across the layer. We characterize the dependence of these quantities on the chemical properties of the mucus gel, the composition of the bath solution, and the molecular mobility of the dissolved anion, and we show that the model predictions are consistent with a large portion of the experimental literature. Our analysis predicts that mucus layers generically slow the diffusive transport of hydrogen, but that chemical binding with the network attenuates this effect.
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Affiliation(s)
- Owen L. Lewis
- Department of Mathematics and Statistics, University of New Mexico
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8
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Aggarwal M, Cogan NG, Lewis OL. Physiological insights into electrodiffusive maintenance of gastric mucus through sensitivity analysis and simulations. J Math Biol 2021; 83:30. [PMID: 34436680 PMCID: PMC8459737 DOI: 10.1007/s00285-021-01643-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 06/24/2021] [Accepted: 07/18/2021] [Indexed: 11/28/2022]
Abstract
It is generally accepted that the gastric mucosa and adjacent mucus layer are critical in the maintenance of a pH gradient from stomach lumen to stomach wall, protecting the mucosa from the acidic environment of the lumen and preventing auto-digestion of the epithelial layer. No conclusive study has shown precisely which physical, chemical, and regulatory mechanisms are responsible for maintaining this gradient. However, experimental work and modeling efforts have suggested that concentration dependent ion-exchange at the epithelial wall, together with hydrogen ion/mucus network binding, may produce the enormous pH gradients seen in vivo. As of yet, there has been no exhaustive study of how sensitive these modeling results are with respect to variation in model parameters, nor how sensitive such a regulatory mechanism may be to variation in physical/biological parameters. In this work, we perform sensitivity analysis (using Sobol' Indices) on a previously reported model of gastric pH gradient maintenance. We quantify the sensitivity of mucosal wall pH (as a proxy for epithelial health) to variations in biologically relevant parameters and illustrate how variations in these parameters affects the distribution of the measured pH values. In all parameter regimes, we see that the rate of cation/hydrogen exchange at the epithelial wall is the dominant parameter/effect with regards to variation in mucosal pH. By careful sensitivity analysis, we also investigate two different regimes representing high and low hydrogen secretion with different physiological interpretations. By complementing mechanistic modeling and biological hypotheses testing with parametric sensitivity analysis we are able to conclude which biological processes must be tightly regulated in order to robustly maintain the pH values necessary for healthy function of the stomach.
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Affiliation(s)
| | - N G Cogan
- Florida State University, Tallahassee, USA
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9
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Al-Shaibi AA, Abdel-Motal UM, Hubrack SZ, Bullock AN, Al-Marri AA, Agrebi N, Al-Subaiey AA, Ibrahim NA, Charles AK, Elawad M, Uhlig HH, Lo B. Human AGR2 Deficiency Causes Mucus Barrier Dysfunction and Infantile Inflammatory Bowel Disease. Cell Mol Gastroenterol Hepatol 2021; 12:1809-1830. [PMID: 34237462 PMCID: PMC8551217 DOI: 10.1016/j.jcmgh.2021.07.001] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 06/29/2021] [Accepted: 07/01/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS The gastrointestinal epithelium plays a crucial role in maintaining homeostasis with the gut microbiome. Mucins are essential for intestinal barrier function and serve as a scaffold for antimicrobial factors. Mucin 2 (MUC2) is the major intestinal gel-forming mucin produced predominantly by goblet cells. Goblet cells express anterior gradient 2 (AGR2), a protein disulfide isomerase that is crucial for proper processing of gel-forming mucins. Here, we investigated 2 siblings who presented with severe infantile-onset inflammatory bowel disease. METHODS We performed whole-genome sequencing to identify candidate variants. We quantified goblet cell numbers using H&E histology and investigated the expression of gel-forming mucins, stress markers, and goblet cell markers using immunohistochemistry. AGR2-MUC2 binding was evaluated using co-immunoprecipitation. Endoplasmic reticulum (ER) stress regulatory function of mutant AGR2 was examined by expression studies in Human Embryonic Kidney 293T (HEK293T) using tunicamycin to induce ER stress. RESULTS Both affected siblings were homozygous for a missense variant in AGR2. Patient biopsy specimens showed reduced goblet cells; depletion of MUC2, MUC5AC, and MUC6; up-regulation of AGR2; and increased ER stress. The mutant AGR2 showed reduced capacity to bind MUC2 and alleviate tunicamycin-induced ER stress. CONCLUSIONS Phenotype-genotype segregation, functional experiments, and the striking similarity of the human phenotype to AGR2-/- mouse models suggest that the AGR2 missense variant is pathogenic. The Mendelian deficiency of AGR2, termed "Enteropathy caused by AGR2 deficiency, Goblet cell Loss, and ER Stress" (EAGLES), results in a mucus barrier defect, the inability to mitigate ER stress, and causes infantile-onset inflammatory bowel disease.
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Affiliation(s)
| | | | | | - Alex N Bullock
- Centre for Medicines Discovery, University of Oxford, Oxford, United Kingdom
| | | | | | | | | | | | - Mamoun Elawad
- Department of Gastroenterology, Sidra Medicine, Doha, Qatar
| | - Holm H Uhlig
- Translational Gastroenterology Unit, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom; Oxford Biomedical Research Centre, Oxford, United Kingdom; Department of Pediatrics, University of Oxford, Oxford, United Kingdom
| | - Bernice Lo
- Research Branch, Sidra Medicine, Doha, Qatar; College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.
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10
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Lewis OL, Keener JP. ENHANCED ELECTRODIFFUSIVE TRANSPORT ACROSS A MUCUS LAYER. SIAM JOURNAL ON APPLIED MATHEMATICS 2021; 81:965-981. [PMID: 34176976 PMCID: PMC8232554 DOI: 10.1137/20m1348327] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/17/2023]
Abstract
Diffusive transport of small ionic species through mucus layers is a ubiquitous phenomenon in physiology. However, some debate remains regarding how the various characteristics of mucus (charge of the polymers themselves, binding affinity of ions with mucus) impact the rate at which small ions may diffuse through a hydrated mucus gel. Indeed it is not even clear if small ionic species diffuse through mucus gel at an appreciably different rate than they do in aqueous solution. Here, we present a mathematical description of the transport of two ionic species (hydrogen and chloride) through a mucus layer based on the Nernst-Planck equations of electrodiffusion. The model explicitly accounts for the binding affinity of hydrogen to the mucus material, as well as the Donnan potential that occurs at the interface between regions with and without mucus. Steady state fluxes of ionic species are quantified, as are their dependencies on the chemical properties of the mucus gel and the composition of the bath solution. We outline a mechanism for generating enhanced diffusive flux of hydrogen across the gel region, and hypothesize how this mechanism may be relevant to the apparently contradictory experimental data in the literature.
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Affiliation(s)
- Owen L Lewis
- Department of Mathematics & Statistics, University of New Mexico
| | - James P Keener
- Department of Mathematics and Department of Bioengineering, University of Utah
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Stenger Moura F, Perioli L, Pagano C, Vivani R, Ambrogi V, Bresolin T, Ricci M, Schoubben A. Chitosan composite microparticles: A promising gastroadhesive system for taxifolin. Carbohydr Polym 2019; 218:343-354. [DOI: 10.1016/j.carbpol.2019.04.075] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Revised: 04/23/2019] [Accepted: 04/24/2019] [Indexed: 02/06/2023]
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Abdulkarim M, Sharma PK, Gumbleton M. Self-emulsifying drug delivery system: Mucus permeation and innovative quantification technologies. Adv Drug Deliv Rev 2019; 142:62-74. [PMID: 30974131 DOI: 10.1016/j.addr.2019.04.001] [Citation(s) in RCA: 66] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Revised: 04/03/2019] [Accepted: 04/05/2019] [Indexed: 12/14/2022]
Abstract
Mucus is a dynamic barrier which covers and protects the underlying mucosal epithelial membrane against bacteria and foreign particles. This protection mechanism extends to include therapeutic macromolecules and nanoparticles (NPs) through trapping of these particles. Mucus is not only a physical barrier that limiting particles movements based on their sizes but it selectively binds with particles through both hydrophilic and lipophilic interactions. Therefore, nano-carriers for mucosal delivery should be designed to eliminate entrapment by the mucus barrier. For this reason, different strategies have been approached for both solid nano-carriers and liquid core nano-carriers to synthesise muco-diffusive nano-carrier. Among these nano-strategies, Self-Emulsifying Drug Delivery System (SEDDS) was recognised as very promising nano-carrier for mucus delivery. The system was introduced to enhance the dissolution and bioavailability of orally administered insoluble drugs. SEDDS has shown high stability against intestinal enzymatic activity and more importantly, relatively rapid permeation characteristics across mucus barrier. The high diffusivity of SEDDS has been tested using various in vitro measurement techniques including both bulk and individual measurement of droplets diffusion within mucus. The selection and processing of an optimum in vitro technique is of great importance to avoid misinterpretation of the diffusivity of SEDDS through mucus barrier. In conclusion, SEDDS is a system with high capacity to diffuse through intestinal mucus even though this system has not been studied to the same extent as solid nano-carriers.
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Affiliation(s)
- Muthanna Abdulkarim
- School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK
| | - Peeyush Kumar Sharma
- School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK; Department of Chemistry, Indian Institute of Technology Ropar, Rupnagar 140001, Punjab, India
| | - Mark Gumbleton
- School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK.
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Saremi K, Rad SK, Tayeby F, Abdulla MA, Karimian H, Majid NA. Gastroprotective activity of a novel Schiff base derived dibromo substituted compound against ethanol-induced acute gastric lesions in rats. BMC Pharmacol Toxicol 2019; 20:13. [PMID: 30770761 PMCID: PMC6377749 DOI: 10.1186/s40360-019-0292-z] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Accepted: 02/08/2019] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Basic function of bromine in body is to activate pepsin production in gastritis with low acidity. The present study encompasses a broad in vivo study to evaluate gastroprotective activity of a novel dibromo substituted Schiff base complex against Sprague Dawley (SD) rats. METHODS 2, 2'-[1, 2-cyclohexanediylbis (nitriloethylidyne)]bis(4-bromophenol) (CNBP) is synthesized via a Schiff base reaction, using the related ketone and diamine as the starting materials. SD rats are divided as normal, ulcer control (5 ml/kg of 10% Tween 20), testing (10 and 20 mg/kg of CNBP) and reference groups (omeprazole 20 mg/kg). Except for the normal group, the rest of the groups are induced gastric ulcer by ethanol 1 h after the pre-treatment. Ulcer area, gastric wall mucus, and acidity of gastric content of the animal stomachs are measured after euthanization. Antioxidant activity of the compound is tested by Ferric reducing antioxidant power (FRAP) test and safety of the compound is identified through acute toxicity by [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Moreover, activities of superoxide dismutase (SOD), catalase (CAT), levels of prostaglandins E2 (PGE2) and also malondialdehyde (MDA) are determined. RESULTS Antioxidant activity of CNBP was approved via FRAP assay. Vast shallow hemorrhagic injury of gastric glandular mucosa was observed in the ulcer group compared to the CNBP-treated animals. Histological evaluations confirmed stomach epithelial defense effect of CNBP with drastic decrease of gastric ulceration, edema and leucocytes penetration of submucosal stratum. Immunostaining exhibited over-expression in HSP70 protein in CNBP-treated groups compared to that of the ulcer group. Also, gastric protein analysis showed low levels of MDA, PGE2 and high activity of SOD and CAT. CONCLUSIONS CNBP with noticeable antioxidant property showed gastroprotective activity in the testing rodents via alteration of HSP70 protein expression. Also, antioxidant enzyme activities which were changed after treatment with CNBP in the animals could be elucidated as its gastroprotective properties.
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Affiliation(s)
- Kamelia Saremi
- Institute of Biological Science, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia
| | - Sima Kianpour Rad
- Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
| | - Faezeh Tayeby
- Institute of Biological Science, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia
| | - Mahmood A. Abdulla
- Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
| | - Hamed Karimian
- School of Medicine, Faculty of Health & Medical Sciences, Taylor’s University, 47500 Subang Jaya, Malaysia
| | - Nazia Abdul Majid
- Institute of Biological Science, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia
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Akiba Y, Kaunitz JD. Gastric carbonic anhydrase IX deficiency: At base, it is all about acid. Acta Physiol (Oxf) 2018; 222:e13047. [PMID: 29389066 DOI: 10.1111/apha.13047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Affiliation(s)
- Y. Akiba
- West Los Angeles Veterans Affairs Medical Center; University of California; Los Angeles CA USA
| | - J. D. Kaunitz
- West Los Angeles Veterans Affairs Medical Center; University of California; Los Angeles CA USA
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Yun SM, Cho JM, Hong KS, Lee DY, Ji SD, Son JG, Kim EH. Gastroprotective effect of mature silkworm, Bombyx mori against ethanol-induced gastric mucosal injuries in rats. J Funct Foods 2017. [DOI: 10.1016/j.jff.2017.10.036] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
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KHODER GHALIA, AL-MENHALI ASMAA, AL-YASSIR FARAH, KARAM SHERIFM. Potential role of probiotics in the management of gastric ulcer. Exp Ther Med 2016; 12:3-17. [PMID: 27347010 PMCID: PMC4906699 DOI: 10.3892/etm.2016.3293] [Citation(s) in RCA: 68] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2015] [Accepted: 03/03/2016] [Indexed: 02/07/2023] Open
Abstract
Gastric ulcer is one of the most common chronic gastrointestinal diseases characterized by a significant defect in the mucosal barrier. Helicobacter pylori (H. pylori) infection and the frequent long-term use of non-steroidal anti-inflammatory drugs are major factors involved in gastric ulcer development. Acid inhibitors and antibiotics are commonly used to treat gastric ulcer. However, in the last few decades, the accumulating evidence for resistance to antibiotics and the side effects of antibiotics and acid inhibitors have drawn attention to the possible use of probiotics in the prevention and treatment of gastric ulcer. Probiotics are live microorganisms that when administered in adequate amounts confer health benefits on the host. Currently, the available experimental and clinical studies indicate that probiotics are promising for future applications in the management of gastric ulcers. This review aims to provide an overview of the general health benefits of probiotics on various systemic and gastrointestinal disorders with a special focus on gastric ulcer and the involved cellular and molecular mechanisms: i) Protection of gastric mucosal barrier; ii) upregulation of prostaglandins, mucus, growth factors and anti-inflammatory cytokines; iii) increased cell proliferation to apoptosis ratio; and iv) induction of angiogenesis. Finally, some of the available data on the possible use of probiotics in H. pylori eradication are discussed.
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Affiliation(s)
- GHALIA KHODER
- Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - ASMA A. AL-MENHALI
- Department of Biology, College of Science, United Arab Emirates University, Al-Ain 17666, United Arab Emirates
| | - FARAH AL-YASSIR
- Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain 17666, United Arab Emirates
| | - SHERIF M. KARAM
- Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain 17666, United Arab Emirates
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Rtibi K, Jabri MA, Selmi S, Souli A, Sebai H, El-Benna J, Amri M, Marzouki L. Gastroprotective effect of carob (Ceratonia siliqua L.) against ethanol-induced oxidative stress in rat. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2015; 15:292. [PMID: 26289579 PMCID: PMC4546091 DOI: 10.1186/s12906-015-0819-9] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/07/2015] [Accepted: 08/11/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND We aimed in the present study, at investigating the gastroprotective effect of carob pods aqueous extract (CPAE) against ethanol-induced oxidative stress in rats as well as the mechanism implicated. METHODS Adult male wistar rats were used and divided into six groups of ten each: control, EtOH (80% v/v, 4 g/kg b.w.), EtOH 80% + various doses of CPAE (500, 1000 and 2000 mg/kg, b.w.) and EtOH + Famotidine (10 mg/kg, p.o.) Animals were perorally (p.o.) pre-treated with CPAE during 15 days and intoxicated with a single oral administration of EtOH (4 g/kg b.w.) for two hours. RESULTS The colorimetric analysis demonstrated that the CPAE exhibited an importance in vitro antioxidant activity against ABTS and DPPH radicals. We found that CPAE pretreatment in vivo, protected against EtOH-induced macroscopic and histological changes induced in stomach mucosa. Carob extract administration also protected against alcohol-induced volume gastric juice decrease. More importantly, We showed that CPAE counteracted EtOH-induced gastric lipoperoxidation, reversed the decrease of sulfhydryl groups (-SH) an hydrogen peroxide (H2O2) levels, and prevented the depletion of antioxidant enzyme activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). CONCLUSIONS These findings suggest that CPAE exerted a potential gastro-protective effect against EtOH-induced oxidative stress in rats, due in part, to its antioxidants properties.
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Affiliation(s)
- Kaïs Rtibi
- Laboratoire de Neurophysiologie Fonctionnelle et Pathologies, Département des Sciences Biologiques, Faculté des Sciences de Tunis. Campus Universitaire El Manar II, Tunis, 2092, Tunisia.
- Laboratoire de Physiologie Fonctionnelle et Valorisation des Bio-Resssources, Institut Supérieur de Biotechnologie de Béja, Université de Jendouba, Avenue Habib Bourguiba, B.P, 382-9000, Béja, Tunisia.
| | - Mohamed Amine Jabri
- Laboratoire de Physiologie Fonctionnelle et Valorisation des Bio-Resssources, Institut Supérieur de Biotechnologie de Béja, Université de Jendouba, Avenue Habib Bourguiba, B.P, 382-9000, Béja, Tunisia
- Laboratoire de Physiologie Intégrée, Faculté des Sciences de Bizerte, 7021 Zarzouna, Bizerte, Tunisia
| | - Slimen Selmi
- Laboratoire de Physiologie Fonctionnelle et Valorisation des Bio-Resssources, Institut Supérieur de Biotechnologie de Béja, Université de Jendouba, Avenue Habib Bourguiba, B.P, 382-9000, Béja, Tunisia
| | - Abdelaziz Souli
- Laboratoire de Neurophysiologie Fonctionnelle et Pathologies, Département des Sciences Biologiques, Faculté des Sciences de Tunis. Campus Universitaire El Manar II, Tunis, 2092, Tunisia
| | - Hichem Sebai
- Laboratoire de Physiologie Fonctionnelle et Valorisation des Bio-Resssources, Institut Supérieur de Biotechnologie de Béja, Université de Jendouba, Avenue Habib Bourguiba, B.P, 382-9000, Béja, Tunisia
- Laboratoire de Physiologie Intégrée, Faculté des Sciences de Bizerte, 7021 Zarzouna, Bizerte, Tunisia
| | - Jamel El-Benna
- INSERM, U1149, Centre de Recherche Sur l'Inflammation, Faculté de Médecine X. Bichat, 75018, Paris, France
| | - Mohamed Amri
- Laboratoire de Neurophysiologie Fonctionnelle et Pathologies, Département des Sciences Biologiques, Faculté des Sciences de Tunis. Campus Universitaire El Manar II, Tunis, 2092, Tunisia
| | - Lamjed Marzouki
- Laboratoire de Physiologie Fonctionnelle et Valorisation des Bio-Resssources, Institut Supérieur de Biotechnologie de Béja, Université de Jendouba, Avenue Habib Bourguiba, B.P, 382-9000, Béja, Tunisia
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Duan JL, Yin J, Ren WK, Wu MM, Chen S, Cui ZJ, Wu X, Huang RL, Li TJ, Yin YL. Pyrrolidine dithiocarbamate restores gastric damages and suppressive autophagy induced by hydrogen peroxide. Free Radic Res 2015; 49:210-8. [PMID: 25471085 DOI: 10.3109/10715762.2014.993627] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
It is well known that gastric barrier is very important for protecting host from various insults. Simultaneously, autophagy serving as a prominent cytoprotective and survival pathway under oxidative stress conditions is being increasingly recognized. Thus, this study was conducted for investigating the effect of pyrrolidine dithiocarbamate (PDTC) on gastric barrier function and autophagy under oxidative stress induced by intragastric administration of hydrogen peroxide (H2O2). The gastric tight junction proteins [zonula occludens-1 (ZO1), occludin, and claudin1], autophagic proteins [microtubule-associated protein light chain 3I(LC3I), LC3II, and beclin1], and nuclear factor kappa B (NF-κB) signaling pathway (p65 and IκB kinase α/β) were determined by Western blot. The results showed that H2O2 exposure disturbed gastric barrier function with decreased expression of ZO1, occludin, and claudin1, and reduced gastric autophagy with decreased conversion of LC3I into LC3II in mice. However, treatment with PDTC restored these adverse effects evidenced by increased expression of ZO1 and claudin1 and increased conversion of LC3I into LC3II. Meanwhile, H2O2 exposure decreased normal human gastric epithelial mucosa cell line (GES-1) viability in a concentration-dependent way. However, after being exposed to H2O2, GES-1 exhibited autophagic response which was inconsistent with our in vivo results in mice, while PDTC failed to decrease autophagy in GES-1 induced by H2O2. Simultaneously, the beneficial effect of PDTC on gastric damage and autophagy in mice might be independent of inhibition of NF-κB. In conclusion, PDTC treatment restores gastric damages and reduced autophagy induced by H2O2. Therefore, PDTC may serve as a potential adjuvant therapy for gastric damages.
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Affiliation(s)
- J L Duan
- Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Hunan Provincial Engineering Research Center of Healthy Livestock, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences , Changsha, Hunan , P. R. China
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Acute toxicity and gastroprotective role of M. pruriens in ethanol-induced gastric mucosal injuries in rats. BIOMED RESEARCH INTERNATIONAL 2013; 2013:974185. [PMID: 23781513 PMCID: PMC3678452 DOI: 10.1155/2013/974185] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/05/2013] [Revised: 04/27/2013] [Accepted: 05/01/2013] [Indexed: 12/29/2022]
Abstract
The investigation was to evaluate gastroprotective effects of ethanolic extract of M. pruriens leaves on ethanol-induced gastric mucosal injuries in rats. Forty-eight rats were divided into 8 groups: negative control, extract control, ulcer control, reference control, and four experimental groups. As a pretreatment, the negative control and the ulcer control groups were orally administered carboxymethylcellulose (CMC). The reference control was administered omeprazole orally (20 mg/kg). The ethanolic extract of M. pruriens leaves was given orally to the extract control group (500 mg/kg) and the experimental groups (62.5, 125, 250, and 500 mg/kg). After 1 h, CMC was given orally to the negative and the extract control groups. The other groups received absolute ethanol. The rats were sacrificed after 1 h. The ulcer control group exhibited significant mucosal injuries with decreased gastric wall mucus and severe damage to the gastric mucosa. The extract caused upregulation of Hsp70 protein, downregulation of Bax protein, and intense periodic acid schiff uptake of glandular portion of stomach. Gastric mucosal homogenate showed significant antioxidant properties with increase in synthesis of PGE2, while MDA was significantly decreased. The ethanolic extract of M. pruriens leaves was nontoxic (<5 g/kg) and could enhance defensive mechanisms against hemorrhagic mucosal lesions.
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Gastroprotective Activity of Polygonum chinense Aqueous Leaf Extract on Ethanol-Induced Hemorrhagic Mucosal Lesions in Rats. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2012; 2012:404012. [PMID: 23365597 PMCID: PMC3544547 DOI: 10.1155/2012/404012] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/01/2012] [Revised: 11/03/2012] [Accepted: 12/05/2012] [Indexed: 01/05/2023]
Abstract
Polygonum chinense is a Malaysian ethnic plant with various healing effects. This study was to determine preventive effect of aqueous leaf extract of P. chinense against ethanol-induced gastric mucosal injury in rats. Sprague Dawley rats were divided into seven groups. The normal and ulcer control groups were orally administered with distilled water. The reference group was orally administered with 20 mg/kg omeprazole. The experimental groups received the extracts 62.5, 125, 250, and 500 mg/kg, accordingly. After sixty minutes, distilled water and absolute ethanol were given (5 mL/kg) to the normal control and the others, respectively. In addition to histology, immunohistochemical and periodic acid schiff (PAS) stains, levels of lipid peroxidation, malondialdehyde (MDA), antioxidant enzymes, and superoxide dismutase (SOD) were measured. The ulcer group exhibited severe mucosal damages. The experimental groups significantly reduced gastric lesions and MDA levels and increased SOD level. Immunohistochemistry of the experimental groups showed upregulation and downregulation of Hsp70 and Bax proteins, respectively. PAS staining in these groups exhibited intense staining as compared to the ulcer group. Acute toxicity study revealed the nontoxic nature of the extract. Our data provide first evidence that P. chinense extract could significantly prevent gastric ulcer.
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Perioli L, Mutascio P, Pagano C. Influence of the Nanocomposite MgAl-HTlc on Gastric Absorption of Drugs: In Vitro and Ex Vivo Studies. Pharm Res 2012; 30:156-66. [DOI: 10.1007/s11095-012-0857-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2012] [Accepted: 08/06/2012] [Indexed: 01/27/2023]
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Benshitrit RC, Levi CS, Tal SL, Shimoni E, Lesmes U. Development of oral food-grade delivery systems: Current knowledge and future challenges. Food Funct 2012; 3:10-21. [DOI: 10.1039/c1fo10068h] [Citation(s) in RCA: 91] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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García-Barrantes PM, Badilla B. Anti-ulcerogenic properties of Quassia amara L. (Simaroubaceae) standardized extracts in rodent models. JOURNAL OF ETHNOPHARMACOLOGY 2011; 134:904-910. [PMID: 21296139 DOI: 10.1016/j.jep.2011.01.052] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/31/2010] [Revised: 01/15/2011] [Accepted: 01/28/2011] [Indexed: 05/30/2023]
Abstract
AIM OF THE STUDY Quassia amara L. is commonly used in Costarican folk medicine. It has been used for the treatment of a broad range of gastrointestinal symptoms such as dyspepsia, gastritis and constipation. In this study, the gastroprotective activity of two standardized extracts of Quassia amara L., Lipro(®) and Ligas(®), was evaluated. MATERIALS AND METHODS Anti-ulcerogenic properties were evaluated in female rats under acute ulcer-induction models (ethanol, indomethacin and hypotermic restraint). To get a deeper insight in the anti-ulcerogenic properties of the extracts, Ligas(®) was evaluated in the Shay rat model. Five parameters were estimated with this model: gastric mucus barrier, non-protein sulfhydril groups (NPSG) in the gastric mucosa, and pH, total acidity and peptic activity of the gastric juice. RESULTS Induction of ulcers by 95% ethanol (0.5 mL per os), indomethacin (100 mg/kgs.c.) and stress (2h in hypothermic restraint) was inhibited significantly with administration of Lipro(®) (p<0.05), in a dosage range from 4.9 mg/kg/d to 48.9 mg/kg/d. Treatment was given for one week. The extract Ligas(®) showed a significant augmentation of NPSG (p<0.05) in a dosage range from 4.0 to 39.7 mg/kg. Ligas(®) did not produce a significant change (p>0.05) in the other indicators. CONCLUSIONS Quassia amara L. standardized extracts, Lipro(®) and Ligas(®), showed an important anti-ulcerogenic effect in acute ulcer induction models. Their effect was related to an increase in gastric barrier mucus and non-protein sulfhydril groups.
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Affiliation(s)
- Pedro Manuel García-Barrantes
- Laboratorio de Fitofarmacología, Instituto de Investigaciones Farmacéuticas, Facultad de Farmacia, Universidad de Costa Rica, Costa Rica. pedro.garcia
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Keely S, Feighery L, Campion DP, O’Brien L, Brayden DJ, Baird AW. Chloride-led Disruption of the Intestinal Mucous Layer Impedes Salmonella Invasion: Evidence for an ‘Enteric Tear’ Mechanism. Cell Physiol Biochem 2011; 28:743-52. [DOI: 10.1159/000335768] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/24/2011] [Indexed: 01/20/2023] Open
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Cu Y, Saltzman WM. Mathematical modeling of molecular diffusion through mucus. Adv Drug Deliv Rev 2009; 61:101-14. [PMID: 19135488 PMCID: PMC2646819 DOI: 10.1016/j.addr.2008.09.006] [Citation(s) in RCA: 88] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2008] [Accepted: 09/22/2008] [Indexed: 01/12/2023]
Abstract
The rate of molecular transport through the mucus gel can be an important determinant of efficacy for therapeutic agents delivered by oral, intranasal, intravaginal/rectal, and intraocular routes. Transport through mucus can be described by mathematical models based on principles of physical chemistry and known characteristics of the mucus gel, its constituents, and of the drug itself. In this paper, we review mathematical models of molecular diffusion in mucus, as well as the techniques commonly used to measure diffusion of solutes in the mucus gel, mucus gel mimics, and mucosal epithelia.
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Affiliation(s)
- Yen Cu
- Department of Biomedical Engineering, Yale University, New Haven, CT 06511
| | - W. Mark Saltzman
- Department of Biomedical Engineering, Yale University, New Haven, CT 06511
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ORAL PHOSPHATIDYLCHOLINE PRESERVES THE GASTROINTESTINAL MUCOSAL BARRIER DURING LPS-INDUCED INFLAMMATION. Shock 2008; 30:729-33. [DOI: 10.1097/shk.0b013e318173e8d4] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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O'Gara EA, Maslin DJ, Nevill AM, Hill DJ. The effect of simulated gastric environments on the anti-Helicobacter activity of garlic oil. J Appl Microbiol 2007; 104:1324-31. [PMID: 18028365 DOI: 10.1111/j.1365-2672.2007.03637.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
AIMS To investigate the effects of simulated gastric conditions upon the anti-Helicobacter pylori effects of garlic oil (GO). METHODS AND RESULTS Time course viability experiments assessed the anti-H. pylori activity of GO (16 and 32 microg ml(-1)) in simulated gastric environments. Rapid anti-H. pylori action of GO was observed in artificial gastric juice. Mucus (1-5%) was strongly protective of H. pylori both alone and in the presence of GO, but its protective effect was antagonized by GO. Peptone (5-15 g l(-1)) caused a dose-dependent reduction in the anti-H. pylori activity of GO. Rapeseed oil (5.7-17 g l(-1)) greatly diminished the anti-H. pylori activity of GO. Dextrin (44 and 133 g l(-1)) exhibited direct anti-H. pylori effects and added to those of GO. Simulated meal mixtures decreased but did not eliminate the anti-H. pylori activity of 32 mug ml(-1) GO. CONCLUSIONS The anti-H. pylori activity of GO was noticeably affected by food materials and mucin. However, substantial activity remained under simulated gastric conditions. Further investigation of the therapeutic potential of GO against H. pylori is therefore warranted. SIGNIFICANCE AND IMPACT OF THE STUDY Garlic oil may be useful as an alternative treatment against H. pylori, a major cause of gastrointestinal infections in humans.
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Affiliation(s)
- E A O'Gara
- Research Institute in Healthcare Science, University of Wolverhampton, School of Applied Sciences, Wolverhampton, United Kingdom.
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N/A, 任 建. N/A. Shijie Huaren Xiaohua Zazhi 2005; 13:2578-2581. [DOI: 10.11569/wcjd.v13.i21.2578] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/26/2023] Open
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Ohta Y, Kamiya Y, Imai Y, Arisawa T, Nakano H. Plaunotol prevents the progression of acute gastric mucosal lesions induced by compound 48/80, a mast cell degranulator, in rats. Pharmacology 2005; 74:182-92. [PMID: 15855831 DOI: 10.1159/000085388] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2004] [Accepted: 03/03/2005] [Indexed: 11/19/2022]
Abstract
We examined the preventive effect of plaunotol, an antiulcer drug, on acute gastric mucosal lesion progression in rats treated once with compound 48/80 (C48/80). Rats treated with C48/80 (0.75 mg/kg BW, i.p.) received plaunotol (10, 25 or 50 mg/kg BW, p.o.) 0.5 h after the treatment at which time gastric mucosal lesions appeared. The gastric mucosa of C48/80-treated rats showed progressed lesions and had increased myeloperoxidase (an index of neutrophil infiltration) activity and thiobarbituric acid reactive substances (an index of lipid peroxidation) content and decreased ascorbic acid and adherent mucus contents and Se-glutathione peroxidase activity at 3 h after C48/80 treatment. Postadministered plaunotol attenuated all these changes dose-dependently. These attenuating effects of plaunotol were not counteracted by pretreatment with indomethacin (5 mg/kg BW, i.p.), a prostaglandin synthesis inhibitor. These results indicate that plaunotol prevents the progression of C48/80-induced acute gastric mucosal lesions in rats possibly by its anti-inflammatory and antioxidant actions, but not by affecting gastric mucosal prostaglandin levels.
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Affiliation(s)
- Yoshiji Ohta
- Department of Chemistry, School of Medicine, Fujita Health University, Toyoake, Japan.
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Kamiya Y, Ohta Y, Imai Y, Arisawa T, Nakano H. A critical role of gastric mucosal ascorbic acid in the progression of acute gastric mucosal lesions induced by compound 48/80 in rats. World J Gastroenterol 2005; 11:1324-32. [PMID: 15761970 PMCID: PMC4250679 DOI: 10.3748/wjg.v11.i9.1324] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the role of gastric mucosal ascorbic acid (AA) in the progression of acute gastric mucosal lesions induced by compound 48/80 (C48/80), a mast cell degranulator, in rats.
METHODS: C48/80 (0.75 mg/kg) was intraperitoneally injected to fasted Wistar rats. Oral administration of AA (10, 50 or 100 mg/kg) was performed 0.5 h after C48/80 treatment. Determinations for gastric mucosal lesion severity and blood flow, and assays for gastric mucosal total AA, reduced AA, oxidized AA, vitamin E, thiobarbituric acid reactive substances (TBARS), adherent mucus, nitrite/nitrate (NOx), non-protein SH (NPSH), and myeloperoxidase (MPO), and serum total AA, reduced AA, oxidized AA, and NOx were conducted 0.5 and 3 h after C48/80 treatment.
RESULTS: Gastric mucosal lesions occurred 0.5 h after C48/80 treatment and progressed at 3 h. Gastric mucosal blood flow decreased 0.5 h after C48/80 treatment but the decrease was recovered at 3 h. Gastric mucosal total AA, reduced AA, vitamin E, and adherent mucus concentrations decreased 3 h after C48/80 treatment. Gastric mucosal oxidized AA concentration remained unchanged after C48/80 treatment. Gastric mucosal NPSH concentration decreased 0.5 h after C48/80 treatment, but the decrease was recovered at 3 h. Gastric mucosal TBARS concentration and MPO activity increased 0.5 h after C48/80 treatment and further increased at 3 h. Serum total AA and reduced AA concentrations increased 0.5 h after C48/80 treatment and further increased at 3 h, while serum oxidized AA concentration increased at 0.5 h. Serum and gastric mucosal NOx concentrations increased 3 h after C48/80 treatment. AA administration to C48/80-treated rats at 0.5 h after the treatment prevented the gastric mucosal lesion progression and the changes in gastric mucosal total AA, reduced AA, vitamin E, adherent mucus, NOx, and TBARS concentrations and MPO activity and serum NOx concentration found at 3 h after the treatment dose-dependently. The AA administration to C48/80-treated rats caused further increases in serum total AA and reduced AA concentrations at 3 h after the treatment dose-dependently.
CONCLUSION: Gastric mucosal AA plays a critical role in the progression of C48/80-induced acute gastric mucosal lesions in rats.
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Affiliation(s)
- Yoshio Kamiya
- Department of Internal Medicine, School of Medicine, Fujita Health University, Toyoake, Aichi 470-1192, Japan
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Ohta Y, Kobayashi T, Imai Y, Inui K, Yoshino J, Nakazawa S. Effect of Gefarnate on Acute Gastric Mucosal Lesion Progression in Rats Treated with Compound 48/80, a Mast Cell Degranulator, in Comparison with That of Teprenone. Biol Pharm Bull 2005; 28:1424-30. [PMID: 16079487 DOI: 10.1248/bpb.28.1424] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
We have reported that teprenone (geranylgeranylacetone), an anti-ulcer drug, prevents acute gastric mucosal lesion progression in rats treated once with compound 48/80 (C48/80), a mast cell degranulator, possibly by suppressing mucus depletion, neutrophil infiltration, and oxidative stress in the gastric mucosa. Herein, we examined the preventive effect of gefarnate (geranyl farnesylacetate), an anti-ulcer drug, on acute gastric mucosal lesion progression in rats treated once with C48/80 (0.75 mg/kg, i.p.) in comparison with that of teprenone, because the chemical structure and anti-ulcer action of gefarnate are similar to those of teprenone. Gefarnate (50, 100 or 200 mg/kg) administered orally at 0.5 h after C48/80 treatment, at which time gastric mucosal lesions appeared, reduced progressive gastric mucosal lesions at 3 h dose-dependently. At 3 h after C48/80 treatment, the gastric mucosa had decreased adherent mucus and hexosamine contents and increased myeloperoxdiase (an index of neutrophil infiltration) and xanthine oxidase activities and thiobarbituric acid reactive substances (an index of lipid peroxidation) content. Post-administered gefarnate attenuated all these changes dose-dependently. These preventive effects of gefarnate were similar to those of teprenone at a dose of 200 mg/kg. Post-administered gefarnate did not affect the increases in serum serotonin and histamine concentrations and the decrease in gastric mucosal blood flow at 3 h after C48/80 treatment like teprenone. These results indicate that orally administered gefarnate prevents acute gastric mucosal lesion progression in C48/80-treated rats possibly by suppressing mucus depletion, neutrophil infiltration, and oxidative stress in the gastric mucosa like teprenone.
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Affiliation(s)
- Yoshiji Ohta
- Department of Chemistry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.
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Ohta Y, Kobayashi T, Inui K, Yoshino J, Kitagawa A, Nakazawa S. Preventive effect of teprenone on acute gastric mucosal lesion progression in compound 48/80-treated rats. Eur J Pharmacol 2004; 487:223-32. [PMID: 15033395 DOI: 10.1016/j.ejphar.2004.01.032] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2003] [Revised: 01/15/2004] [Accepted: 01/28/2004] [Indexed: 11/15/2022]
Abstract
The preventive effect of teprenone (6,10,14,18-teramethyl-5,9,13,17-nonadecatetaene-2-one), an anti-ulcer drug, on acute gastric mucosal lesion progression was examined in rats with a single intraperitoneal (i.p.) injection of compound 48/80 (0.75 mg/kg). Teprenone (20, 100 or 200 mg/kg), which was orally administered 0.5 h after compound 48/80 treatment at which time gastric mucosal lesions appeared, prevented gastric mucosal lesion development at 3 h after the treatment dose-dependently. Gastric mucosal tissues of compound 48/80-treated rats showed increases in myeloperoxidase (an index of neutrophil infiltration) and xanthine oxidase activities and thiobarbituric acid reactive substances (an index of lipid peroxidation) content and decreases in Se-glutathione peroxidase activity and hexosamine and vitamin E contents at 3 h after the treatment. Post-administered teprenone attenuated all these changes dose-dependently. These results indicate that teprenone prevents acute gastric mucosal lesion progression in compound 48/80-treated rats possibly by suppressing gastric mucus depletion, neutrophil infiltration and oxidative stress in the gastric mucosal tissue.
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Affiliation(s)
- Yoshiji Ohta
- Department of Chemistry, School of Medicine, Fujita Health University, Toyoake, Aichi 470-1192, Japan.
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Ohta Y, Kobayashi T, Inui K, Yoshino J, Nakazawa S. Protective effect of teprenone against acute gastric mucosal lesions induced by compound 48/80, a mast cell degranulator, in rats. J Pharmacol Sci 2004; 93:337-46. [PMID: 14646252 DOI: 10.1254/jphs.93.337] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
Abstract
The protective effect of teprenone, an anti-ulcer drug, against acute gastric mucosal lesions was examined in rats with a single intraperitoneal injection of compound 48/80 (0.75 mg/kg). Teprenone (50, 100, or 200 mg/kg) was orally administered 0.5 h before compound 48/80 treatment. Administered teprenone prevented gastric mucosal lesion development found at 3 h after compound 48/80 treatment dose-dependently, although no dose of teprenone affected the decreased gastric mucosal blood flow and increased serum serotonin and histamine concentrations found at 3 h after the treatment. Increases in the activities of myeloperoxdiase (an index of neutrophil infiltration) and xanthine oxidase and the content of thiobarbituric acid reactive substances (an index of lipid peroxidation) and decreases in the contents of hexosamine (a marker of gastric mucus) and adherent mucus occurred in gastric mucosal tissues at 3 h after compound 48/80 treatment. Administered teprenone dose-dependently attenuated all these changes found at 3 h after compound 48/80 treatment. These results indicate that orally administered teprenone protects against compound 48/80-induced acute gastric mucosal lesions in rats possibly through its stimulatory action on gastric mucus synthesis and secretion and its inhibitory action on neutrophil infiltration and enhanced lipid peroxidation in the gastric mucosal tissue.
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Affiliation(s)
- Yoshiji Ohta
- Department of Chemistry, School of Medicine, Fujita Health University, Toyoake, Aichi, Japan.
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Ohta Y, Nishida K. L-arginine protects against stress-induced gastric mucosal lesions by preserving gastric mucus. Clin Exp Pharmacol Physiol 2002; 29:32-8. [PMID: 11906459 DOI: 10.1046/j.1440-1681.2002.03607.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
1. We have shown that exogenously administered L-arginine protects against water immersion restraint (WIR) stress-induced gastric mucosal lesions in rats through preservation of nitric oxide (NO) generation via constitutive nitric oxide synthase (cNOS), but not inducible nitric oxide synthase (iNOS), in the gastric mucosa. We have also indicated that impaired gastric mucus synthesis and secretion occur through a decrease in gastric cNOS activity in WIR-stressed rats. Therefore, in the presesnt study, we examined whether exogenously administered L-arginine exerts a protective effect against WIR stress-induced gastric mucosal lesions in rats through preservation of gastric mucus synthesis and secretion by NO generated from the administered amino acid via cNOS in the gastric mucosa. 2. Rats were subjected to WIR stress for 3 and 6 h. Either L-arginine (150-600 mg/kg) or D-arginine (600 mg/kg) was injected intraperitoneally 0.5 h prior to WIR stress. Either N(G)-monomethyl L-arginine (L-NMMA; 100 mg/kg) or N(G)-monomethyl D-arginine (D-NMMA; 100 mg/kg) was injected subcutaneously 0.5 h prior to WIR stress. Total NOS, cNOS, iNOS, nitrite and nitrate (breakdown products of NO), hexosamine (an index of gastric mucin) and adherent mucus were assayed in the gastric mucosa. 3. Pretreatment with L-arginine, but not D-arginine, protected against gastric mucosal lesions in rats subjected to WIR stress for 3 and 6 h in a dose-dependent manner. Pretreatment with L-arginine, but not D-arginine, attenuated decreases in hexosamine and adherent mucus concentrations and cNOS activity and increases in total NOS and iNOS activities and nitrite/nitrate concentration in the gastric mucosal tissue of rats subjected to WIR stress for 3 and 6 h in a dose-dependent manner. Both the protective effect of L-arginine against gastric mucosal lesions and the attenuating effect of the amino acid on the decreases in gastric mucosal hexosamine and adherent mucus concentrations and cNOS activity in rats subjected to WIR stress for 6 h were counteracted by cotreatment with L-NMMA, a nitric oxide synthase inhibitor, but not D-NMMA. 4. These results suggest that exogenously administered L-arginine exerts a protective effect against stress-induced gastric mucosal lesions in rats at least partly through preservation of gastric mucus synthesis and secretion by NO produced from the administered amino acid via cNOS in gastric mucosal tissue.
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Affiliation(s)
- Yoshiji Ohta
- Department of Chemistry, School of Medicine, Fujita Health University, Toyoake, Aichi, Japan.
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Ferri D, Liquori GE, Natale L, Santarelli G, Scillitani G. Mucin histochemistry of the digestive tract of the red-legged frog Rana aurora aurora. Acta Histochem 2001; 103:225-37. [PMID: 11368102 DOI: 10.1078/0065-1281-00582] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Mucous cells from the digestive tract of the red-legged frog, Rana aurora aurora, were examined by standard histochemical methods and by lectin histochemistry. Two different goblet cell types were found in the oesophageal epithelium. Type I cells produced acidic glycoproteins with beta1,4GlcNAc oligomers, Gal beta1,3GalNAc sequences, sulphated esters on internal residues and abundant non-O-acylated terminal sialic acid bound to penultimate GalNAc. These cells also reacted with Con-A after periodate oxidation-borohydride reduction (PCS). Type II goblet cells mainly differed from type I cells in their negative reaction with PCS. Oesophageal glands consisted of mucous and serous cells. Mucous cells produced neutral stable class III mucosubstances with GalNAc, beta1,4GlcNAc and Gal beta1,3GalNAc residues. Gastric surface cells produced sulpho-sialoglycoproteins with Gal beta1,3GalNAc residues and Gal beta1,3GalNAc-sialic acid as terminal sequences. These cells did not contain stable class III mucosubstances. The mucus produced by foveolar cells was similar in composition but did not contain sulphated groups and was rich in GalNAc residues. The fundic glands consisted of mucous neck cells, endocrine cells and oxyntic cells. The neck cells produced neutral mucins containing D-mannose and/or D-glucose, beta1,4GlcNAc oligomers and Gal beta1,3GalNAc terminal dimers and were PCS-positive. Pyloric glands were of the mucus-secreting type, which produced glycoproteins with the same basic features as those produced in fundic neck cells. A single type of intestinal goblet cells produced acidic glycoproteins rich in beta1,4GlcNAc oligomers, sulphated esters on oligosaccharide chains and terminal O-acylated sialic acid bound to penultimate Gal beta1,3GalNAc. The different carbohydrate structures observed along the digestive tract of the frog may reflect specific functions of the mucus.
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Affiliation(s)
- D Ferri
- Department of Zoology, University of Bari, Italy.
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