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Husori DI, Marianne M, Lubis NDS, Yusfa KL, Angela IFD. Evaluation of Gastroprotective Effect from Phaleria macrocarpa Fruits Extract on Gastric Ulcer in Male Wistar Rats. Open Access Maced J Med Sci 2022. [DOI: 10.3889/oamjms.2022.8242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Abstract
BACKGROUND: The long-term use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) triggers gastric mucosal damage and causes ulcers. Meanwhile, studies showed that God's crown fruit (Phaleria macrocarpa) contains secondary metabolites of flavonoids and tannins that can protect the gastric mucosa.
AIM: This study aims to determine the gastroprotective effect of P. macrocarpa ethanolic extracts against gastric ulcers in rats induced with acetosal and ethanol. The extracts were obtained by maceration method using 96% ethanol as solvent.
METHODS: The male rats used were divided into 7 groups for each test with ethanol and acetosal induction. Each group consisted of 5 rats, namely normal control, induction, carrier, positive control (sucralfate 360 mg/kg BW and omeprazole 3.6 mg/kg BW), and extract doses 100, 200, and 400 mg/kg body weight. All groups were given treatment for 7 days except normal and induction controls. On day 6, rats were fasted for 36 hours and induced with acetosal/ethanol. In ethanol induction, the animal was sacrificed after 10 hours of immersion while in acetosal, the animal was sacrificed 6 hours later. The stomach section was taken for macroscopic, microscopic parameters and gastric acid secretion examination.
RESULTS: The results of phytochemical screening showed that the extract contained flavonoids, tannins, saponins, alkaloids, and glycosides. In acetosal-induced ulcers, the administration of one dose of the extract reduced the number and score of ulcers, repair epithelial cells, increase pH, and total gastric acidity. Furthermore, the percentage of ulcer inhibition at the extract dose of 400 mg/kg BW was 91.91±3.74% in ethanol induction, and 59±13.08% in acetosal.
CONCLUSION: The ethanolic extract of P. macrocarpa has a gastroprotective effect on acetosal-induced gastric ulcer rats.
Keywords: Phaleria macrocarpa, Mahkota Dewa fruit, gastroprotective, gastric ulcers, extract
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Therapeutic approach of adipose-derived mesenchymal stem cells in refractory peptic ulcer. Stem Cell Res Ther 2021; 12:515. [PMID: 34565461 PMCID: PMC8474857 DOI: 10.1186/s13287-021-02584-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Accepted: 09/04/2021] [Indexed: 12/14/2022] Open
Abstract
Peptic ulcer is one of the most common gastrointestinal tract disorders worldwide, associated with challenges such as refractory morbidity, bleeding, interference with use of anticoagulants, and potential side effects associated with long-term use of proton pump inhibitors. A peptic ulcer is a defect in gastric or duodenal mucosa extending from muscularis mucosa to deeper layers of the stomach wall. In most cases, ulcers respond to standard treatments. However, in some people, peptic ulcer becomes resistant to conventional treatment or recurs after initially successful therapy. Therefore, new and safe treatments, including the use of stem cells, are highly favored for these patients. Adipose-derived mesenchymal stem cells are readily available in large quantities with minimal invasive intervention, and isolation of adipose-derived mesenchymal stromal stem cells (ASC) produces large amounts of stem cells, which are essential for cell-based and restorative therapies. These cells have high flexibility and can differentiate into several types of cells in vitro. This article will investigate the effects and possible mechanisms and signaling pathways of adipose tissue-derived mesenchymal stem cells in patients with refractory peptic ulcers.
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Abd El Hady WE, Soliman OAEA, El Sabbagh HM, Mohamed EA. Glutaraldehyde-crosslinked chitosan-polyethylene oxide nanofibers as a potential gastroretentive delivery system of nizatidine for augmented gastroprotective activity. Drug Deliv 2021; 28:1795-1809. [PMID: 34470551 PMCID: PMC8428272 DOI: 10.1080/10717544.2021.1971796] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
Nizatidine (NIZ), a histamine H2-receptor antagonist, is soluble and stable in the stomach, however, it exhibits a short half-life and a rapid clearance. Therefore, chitosan (CS) and polyethylene oxide (PEO) nanofibers (NFs) at different weight ratios were prepared by electrospinning and characterized. The selected uncrosslinked and glutaraldehyde-crosslinked NFs were investigated regarding floating, solid-state characteristics, in vitro release, and in vitro cytotoxicity. The cytoprotective activity against ethanol-induced gastric injury in rats was evaluated through macroscopical, histopathological, immunohistochemical, and oxidative stress examinations. NFs based on 8:2 CS:PEO exhibited the smallest diameter (119.17 ± 22.05 nm) and the greatest mucoadhesion (22.82 ± 3.21 g/cm2), so they were crosslinked with glutaraldehyde. Solid-state characterization indicated polymers interaction, a successful crosslinking, and NIZ dispersion in NFs. Crosslinking maintained swollen mats at pH 1.2 (swelling% = 29.47 ± 3.50% at 24 h), retarded their erosion at pH 6.8 (swelling%= 84.64 ± 4.91% vs. 25.40 ± 0.79% for the uncrosslinked NFs at 24 h), augmented the floating up to 24 h vs. 10 min for the uncrosslinked NFs at pH 1.2 and prolonged the drug release (%drug released ≥ 93% at 24 h vs. 4 and 5 h for the uncrosslinked NFs at pHs 1.2 and 6.8, respectively). The viability of Caco-2 cells ≥ 86.87 ± 6.86% revealed NFs biocompatibility and unreacted glutaraldehyde removal. Crosslinking of 8:2 CS:PEO NFs potentiated the antiulcer activity (38.98 vs. 8.67 for the uncrosslinked NFs) as well as it preserved the gastric wall architecture, COX-2 expression, and oxidative stress markers levels of the normal rats.
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Fordjour L, Cai C, Bronshtein V, Bronshtein M, Aranda JV, Beharry KD. Growth factors in the fetus and pre-adolescent offspring of hyperglycemic rats. Diab Vasc Dis Res 2021; 18:14791641211011025. [PMID: 33913361 PMCID: PMC8482349 DOI: 10.1177/14791641211011025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND Maternal hyperglycemia influences childhood metabolic syndrome, including obesity and hyperglycemia. We tested the hypothesis that the maternal hyperglycemia influences growth factors in the fetal and pre-adolescent offspring. METHODS Hyperglycemia was induced in pregnant rats on embryonic day (E)16 using streptozocin followed by implantation with insulin or placebo pellets at embryonic day 18 (E18). Fetuses at E20 and pre-adolescent pups at postnatal day 14 (P14) were studied: (1) normal untreated controls (CTL) at E20; (2) hyperglycemic placebo-treated (HPT) at E20; (3) hyperglycemic insulin-treated (HIT) at E20; (4) CTL at P14; and (5) HIT at P14. Fetal and pre-adolescent growth factors were determined. RESULTS Biomarkers of hypoxia were elevated in the HPT group at E20. This group did not survive to term. Maternal insulin improved fetal survival despite lower fetal body weight at E20, however, at normal birth (postnatal day 0 (P0)) and at P14, body weights and blood glucose were higher than CTL. These high levels correlated with aberrant growth factors. Maternal hyperglycemia influenced glucose-6-phosphate dehydrogenase, glucagon, insulin, interleukin-10, and leptin genes. CONCLUSIONS The impact of maternal hyperglycemia on pre-adolescent glucose and body weight was not a consequence of maternal overnutrition. This suggests an independent link which may affect offspring metabolic health in later life.
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Affiliation(s)
- Lawrence Fordjour
- Division of Neonatal-Perinatal
Medicine, Department of Pediatrics, State University of New York, Downstate Medical
Center, Brooklyn, NY, USA
| | - Charles Cai
- Division of Neonatal-Perinatal
Medicine, Department of Pediatrics, State University of New York, Downstate Medical
Center, Brooklyn, NY, USA
| | - Vadim Bronshtein
- Division of Neonatal-Perinatal
Medicine, Department of Pediatrics, State University of New York, Downstate Medical
Center, Brooklyn, NY, USA
| | - Mayan Bronshtein
- Division of Neonatal-Perinatal
Medicine, Department of Pediatrics, State University of New York, Downstate Medical
Center, Brooklyn, NY, USA
| | - Jacob V Aranda
- Division of Neonatal-Perinatal
Medicine, Department of Pediatrics, State University of New York, Downstate Medical
Center, Brooklyn, NY, USA
- Department of Ophthalmology, State
University of New York, Downstate Medical Center, Brooklyn, NY, USA
- State University of New York Eye
Institute, New York, NY, USA
| | - Kay D Beharry
- Division of Neonatal-Perinatal
Medicine, Department of Pediatrics, State University of New York, Downstate Medical
Center, Brooklyn, NY, USA
- Department of Ophthalmology, State
University of New York, Downstate Medical Center, Brooklyn, NY, USA
- State University of New York Eye
Institute, New York, NY, USA
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5
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The quest for effective pharmacological suppression of neointimal hyperplasia. Curr Probl Surg 2020; 57:100807. [PMID: 32771085 DOI: 10.1016/j.cpsurg.2020.100807] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Accepted: 04/22/2020] [Indexed: 12/15/2022]
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6
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Périco LL, Rodrigues VP, Ohara R, Bueno G, Nunes VVA, dos Santos RC, Camargo ACL, Júnior LAJ, de Andrade SF, Steimbach VMB, da Silva LM, da Rocha LRM, Vilegas W, dos Santos C, Hiruma-Lima CA. Sex-specific effects of Eugenia punicifolia extract on gastric ulcer healing in rats. World J Gastroenterol 2018; 24:4369-4383. [PMID: 30344421 PMCID: PMC6189849 DOI: 10.3748/wjg.v24.i38.4369] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Revised: 07/11/2018] [Accepted: 08/01/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the sex-specific effects of a hydroalcoholic extract from Eugenia punicifolia (HEEP) leaves on gastric ulcer healing.
METHODS In this rat study involving males, intact (cycling) females, and ovariectomized females, gastric ulcers were induced using acetic acid. A vehicle, lansoprazole, or HEEP was administered for 14 d after ulcer induction. Body weight was monitored throughout the treatment period. At the end of treatment, the rats were euthanized and the following in vivo and in vitro investigations were performed: macroscopic examination of the lesion area and organ weights, biochemical analysis, zymography, and evaluation of protein expression levels. Additionally, the concentration-dependent effect of HEEP was evaluated in terms of subacute toxicity and cytotoxicity.
RESULTS Compared to the vehicle, HEEP demonstrated a great healing capacity by substantially reducing the ulcerative lesion area in males (52.44%), intact females (85.22%), and ovariectomized females (65.47%), confirming that HEEP accelerates the healing of acetic acid-induced gastric lesions and suggesting that this effect is modulated by female sex hormones. The antiulcer effect of HEEP was mediated by prostaglandin E2 only in male rats. Overall, the beneficial effect of HEEP was the highest in intact females. Notably, HEEP promoted the expression of vascular endothelial growth factor (intact vs ovariectomized females) and decreased the expression of Caspase-8 and Bcl-2 (intact female vs male or ovariectomized female). Additionally, HEEP enhanced fibroblast proliferation and migration into a wounded area in vitro, confirming its healing effect. Finally, no sign of subacute toxicity or cytotoxicity of HEEP was observed.
CONCLUSION In gastric ulcers, HEEP-induced healing (modulated by female sex hormones; in males, mediated by prostaglandin) involves extracellular matrix remodeling, with gastric mucosa cell proliferation and migration.
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Affiliation(s)
- Larissa Lucena Périco
- Department of Physiology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18618-970, São Paulo, Brazil
| | - Vinícius Peixoto Rodrigues
- Department of Physiology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18618-970, São Paulo, Brazil
| | - Rie Ohara
- Department of Physiology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18618-970, São Paulo, Brazil
| | - Gabriela Bueno
- Department of Physiology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18618-970, São Paulo, Brazil
| | - Vânia Vasti Alfieri Nunes
- Department of Physiology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18618-970, São Paulo, Brazil
| | - Raquel Cássia dos Santos
- Laboratory of Bioactive Compounds, São Francisco University, Bragança Paulista 12916-900, São Paulo, Brazil
| | - Ana Carolina Lima Camargo
- Department of Morphology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18618-970, São Paulo, Brazil
| | - Luis Antônio Justulin Júnior
- Department of Morphology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18618-970, São Paulo, Brazil
| | - Sérgio Faloni de Andrade
- Programa de Pós-graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí - UNIVALI, Itajaí 88302-901, Santa Catarina, Brazil
| | - Viviane Miranda Bispo Steimbach
- Programa de Pós-graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí - UNIVALI, Itajaí 88302-901, Santa Catarina, Brazil
| | - Luísa Mota da Silva
- Programa de Pós-graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí - UNIVALI, Itajaí 88302-901, Santa Catarina, Brazil
| | - Lúcia Regina Machado da Rocha
- Department of Physiology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18618-970, São Paulo, Brazil
| | - Wagner Vilegas
- Coastal Campus of São Vicente, São Paulo State University (UNESP), São Vicente 11330-900, São Paulo, Brazil
| | - Catarina dos Santos
- Department of Biological Science, Faculty of Sciences and Languages, São Paulo State University (UNESP), Assis 19806-900, São Paulo, Brazil
| | - Clélia Akiko Hiruma-Lima
- Department of Physiology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18618-970, São Paulo, Brazil
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Abstract
The rapidly declining prevalence of Helicobacter pylori infection and widespread use of potent anti-secretory drugs means peptic ulcer disease has become substantially less prevalent than it was two decades ago. Management has, however, become more challenging than ever because of the threat of increasing antimicrobial resistance worldwide and widespread use of complex anti-thrombotic therapy in the ageing population. Peptic ulcers not associated with H pylori infection or the use of non-steroidal anti-inflammatory drugs are now also imposing substantial diagnostic and therapeutic challenges. This Seminar aims to provide a balanced overview of the latest advances in the pathogenetic mechanisms of peptic ulcers, guidelines on therapies targeting H pylori infection, approaches to treatment of peptic ulcer complications associated with anti-inflammatory analgesics and anti-thrombotic agents, and the unmet needs in terms of our knowledge and management of this increasingly challenging condition.
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Affiliation(s)
- Angel Lanas
- Service of Digestive Diseases, University Clinic Hospital Lozano Blesa, University of Zaragoza, IIS Aragón, CIBEREHD, Zaragoza, Spain.
| | - Francis K L Chan
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
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8
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Martin GR, Wallace JL. Gastrointestinal Inflammation: A Central Component of Mucosal Defense and Repair. Exp Biol Med (Maywood) 2016; 231:130-7. [PMID: 16446488 DOI: 10.1177/153537020623100202] [Citation(s) in RCA: 95] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
The mucosal layer of the gastrointestinal (GI) tract is able to resist digestion by the endogenous substances that we secrete to digest foodstuffs. So-called “mucosal defense” is multifactorial and can be modulated by a wide range of substances, many of which are classically regarded as inflammatory mediators. Damage to the GI mucosa, and its subsequent repair, are also modulated by various inflammatory mediators. In this article, we provide a review of some of the key Inflammatory mediators that modulate GI mucosal defense, Injury, and repair. Among the mediators discussed are nitric oxide, polyamines, the elcosanolds (prostaglandins and II-poxlns), protease-activated receptors, and cytokines. Many of these endogenous factors, or the enzymes involved in their synthesis, are considered potential therapeutic targets for the treatment of diseases of the digestive tract that are characterized by Inflammation and ulceration.
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Affiliation(s)
- Gary R Martin
- Mucosal Inflammation Research Group, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada
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9
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Salem Sokar S, Elsayed Elsayad M, Sabri Ali H. Serotonin and histamine mediate gastroprotective effect of fluoxetine against experimentally-induced ulcers in rats. J Immunotoxicol 2016; 13:638-51. [PMID: 27000965 DOI: 10.3109/1547691x.2016.1145158] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Research in the treatment of gastric ulcer has involved the investigation of new alternatives, such as anti-depressant drugs. The present study was designed to investigate the gastroprotective effects of fluoxetine against indomethacin and alcohol induced gastric ulcers in rats and the potential mechanisms of that effect. Fluoxetine (20 mg/kg) was administered IP for 14 days. For comparative purposes, other rats were treated with ranitidine (30 mg/kg). Thereafter, after 24 h of fasting, INDO (100 mg/kg) or absolute alcohol (5 ml/kg) was administered to all rats (saline was administered to naïve controls) and rats in each group were sacrificed 5 h (for INDO rats) or 1 h (for alcohol rats) later. Macroscopic examination revealed that both fluoxetine and ranitidine decreased ulcer scores in variable ratios, which was supported by microscopic histopathological examination. Biochemical analysis of fluoxetine- or ranitidine-pre-treated host tissues demonstrated reductions in tumor necrosis factor (TNF)-α and myeloperoxidase (MPO) levels and concomitant increases in gastric pH, nitric oxide (NO) and reduced glutathione (GSH) contents. Fluoxetine, more than ranitidine, also resulted in serotonin and histamine levels nearest to control values. Moreover, immuno-histochemical analysis showed that fluoxetine markedly enhanced expression of cyclo-oxygenases COX-1 and COX-2 in both models; in comparison, ranitidine did not affect COX-1 expression in either ulcer model but caused moderate increases in COX-2 expression in INDO-induced hosts and high expression in alcohol-induced hosts. The results here indicated fluoxetine exhibited better gastroprotective effects than ranitidine and this could be due to anti-secretory, anti-oxidant, anti-inflammatory and anti-histaminic effects of the drug, as well as a stabilization of gastric serotonin levels.
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Affiliation(s)
- Samia Salem Sokar
- a Department of Pharmacology and Toxicology, Faculty of Pharmacy , Tanta University , Egypt
| | - Mageda Elsayed Elsayad
- a Department of Pharmacology and Toxicology, Faculty of Pharmacy , Tanta University , Egypt
| | - Hend Sabri Ali
- a Department of Pharmacology and Toxicology, Faculty of Pharmacy , Tanta University , Egypt
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10
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McGettigan MJ, Menias CO, Gao ZJ, Mellnick VM, Hara AK. Imaging of Drug-induced Complications in the Gastrointestinal System. Radiographics 2016; 36:71-87. [DOI: 10.1148/rg.2016150132] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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11
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Short SS, Wang J, Castle SL, Fernandez GE, Smiley N, Zobel M, Pontarelli EM, Papillon SC, Grishin AV, Ford HR. Low doses of celecoxib attenuate gut barrier failure during experimental peritonitis. J Transl Med 2013; 93:1265-75. [PMID: 24126890 PMCID: PMC3966546 DOI: 10.1038/labinvest.2013.119] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2013] [Revised: 09/13/2013] [Accepted: 09/14/2013] [Indexed: 02/08/2023] Open
Abstract
The intestinal barrier becomes compromised during systemic inflammation, leading to the entry of luminal bacteria into the host and gut origin sepsis. Pathogenesis and treatment of inflammatory gut barrier failure is an important problem in critical care. In this study, we examined the role of cyclooxygenase-2 (COX-2), a key enzyme in the production of inflammatory prostanoids, in gut barrier failure during experimental peritonitis in mice. I.p. injection of LPS or cecal ligation and puncture (CLP) increased the levels of COX-2 and its product prostaglandin E2 (PGE2) in the ileal mucosa, caused pathologic sloughing of the intestinal epithelium, increased passage of FITC-dextran and bacterial translocation across the barrier, and increased internalization of the tight junction (TJ)-associated proteins junction-associated molecule-A and zonula occludens-1. Luminal instillation of PGE2 in an isolated ileal loop increased transepithelial passage of FITC-dextran. Low doses (0.5-1 mg/kg), but not a higher dose (5 mg/kg) of the specific COX-2 inhibitor Celecoxib partially ameliorated the inflammatory gut barrier failure. These results demonstrate that high levels of COX-2-derived PGE2 seen in the mucosa during peritonitis contribute to gut barrier failure, presumably by compromising TJs. Low doses of specific COX-2 inhibitors may blunt this effect while preserving the homeostatic function of COX-2-derived prostanoids. Low doses of COX-2 inhibitors may find use as an adjunct barrier-protecting therapy in critically ill patients.
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Affiliation(s)
- Scott S. Short
- Division of Pediatric Surgery, Children’s Hospital Los Angeles, Los Angeles, CA,Department of Surgery, University of Southern California, Los Angeles, CA
| | - Jin Wang
- Division of Pediatric Surgery, Children’s Hospital Los Angeles, Los Angeles, CA
| | - Shannon L. Castle
- Division of Pediatric Surgery, Children’s Hospital Los Angeles, Los Angeles, CA,Department of Surgery, University of Southern California, Los Angeles, CA
| | | | - Nancy Smiley
- Division of Pediatric Surgery, Children’s Hospital Los Angeles, Los Angeles, CA
| | - Michael Zobel
- Division of Pediatric Surgery, Children’s Hospital Los Angeles, Los Angeles, CA
| | - Elizabeth M. Pontarelli
- Division of Pediatric Surgery, Children’s Hospital Los Angeles, Los Angeles, CA,Department of Surgery, University of Southern California, Los Angeles, CA
| | - Stephanie C. Papillon
- Division of Pediatric Surgery, Children’s Hospital Los Angeles, Los Angeles, CA,Department of Surgery, University of Southern California, Los Angeles, CA
| | - Anatoly V. Grishin
- Division of Pediatric Surgery, Children’s Hospital Los Angeles, Los Angeles, CA,Department of Surgery, University of Southern California, Los Angeles, CA
| | - Henri R. Ford
- Division of Pediatric Surgery, Children’s Hospital Los Angeles, Los Angeles, CA,Department of Surgery, University of Southern California, Los Angeles, CA
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12
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Dharmani P, De Simone C, Chadee K. The probiotic mixture VSL#3 accelerates gastric ulcer healing by stimulating vascular endothelial growth factor. PLoS One 2013; 8:e58671. [PMID: 23484048 PMCID: PMC3590171 DOI: 10.1371/journal.pone.0058671] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2012] [Accepted: 02/07/2013] [Indexed: 12/12/2022] Open
Abstract
Studies assessing the effect and mechanism of probiotics on diseases of the upper gastrointestinal tract (GI) including gastric ulcers are limited despite extensive work and promising results of this therapeutic option for other GI diseases. In this study, we investigated the mechanisms by which the probiotic mixture VSL#3 (a mixture of eight probiotic bacteria including Lactobacilli, Bifidobacteria and Streptococcus species) heals acetic acid induced gastric ulcer in rats. VSL#3 was administered orally at low (6×109 bacteria) or high (1.2×1010 bacteria) dosages from day 3 after ulcer induction for 14 consecutive days. VSL#3 treatments significantly enhanced gastric ulcer healing in a dose-dependent manner. To assess the mechanism(s) whereby VSL#3 exerted its protective effects, we quantified the gene expression of several pro-inflammatory cytokines, protein and expression of stomach mucin-Muc5ac, regulatory cytokine-IL-10, COX-2 and various growth factors. Of all the components examined, only expression and protein production of VEGF was increased 332-fold on day 7 in the ulcerated tissues of animals treated with VSL#3. Predictably, animals treated with VEGF neutralizing antibody significantly delayed gastric ulcer healing in VSL#3 treated animals. This is the first report to demonstrate high efficacy of the probiotic mixture VSL#3 in enhancing gastric ulcer healing. Probiotic efficacy was effective at higher concentrations of VSL#3 by specifically increasing the expression and production of angiogenesis promoting growth factors, primarily VEGF.
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Affiliation(s)
- Poonam Dharmani
- Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada
| | - Claudio De Simone
- Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy
| | - Kris Chadee
- Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada
- * E-mail:
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13
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Iwanaga K, Murata T, Hori M, Ozaki H. Purinergic P2Y1 receptor signaling mediates wound stimuli-induced cyclooxygenase-2 expression in intestinal subepithelial myofibroblasts. Eur J Pharmacol 2013; 702:158-64. [PMID: 23376159 DOI: 10.1016/j.ejphar.2013.01.025] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2012] [Revised: 01/09/2013] [Accepted: 01/16/2013] [Indexed: 12/17/2022]
Abstract
Intestinal subepithelial myofibroblasts (ISMFs) are crucial for barrier formation against inflammatory stimuli. Physical injury induces cyclooxygenase-2 (COX-2) expression, which accelerates wound healing by ISMFs. However, the mechanism of COX-2 induction remains unclear. Physically damaged cells release ATP. Here, we investigate the role of ATP-purinergic signaling in wound-induced COX-2 induction in ISMFs. By 24h post-injury, bovine ISMFs had migrated to and closed the wounded area. A COX inhibitor, indomethacin or a purinergic P2 receptor antagonist, suramin, inhibited wound healing. However, additional treatment with indomethacin did not influence wound healing in suramin-treated ISMFs. RT-PCR showed an increase in COX-2 mRNA expression 2h post-injury, which was inhibited by suramin. These results suggest that ATP mediates wound-induced COX-2 elevation. We next assessed the contribution of various purinergic receptors in COX-2 induction. An ATP analog, ATPγS and a purinergic P2Y1, 11-13 receptors agonist, ADP, were among the agents tested which increased COX-2 expression. ATPγS-induced COX-2 mRNA expression was suppressed by suramin or a purinergic P2Xs, P2Y1, 4, 6, and 13 receptors antagonist, PPADS. These data suggest the involvement of Gq-coupled purinergic P2Y1 receptor or Gi-coupled purinergic P2Y13 receptor in COX-2 induction. U73122, an inhibitor of phospholipase C, which is a downstream signal of Gq protein, showed suppression of COX-2 mRNA expression. However, pertussis toxin, a Gi inhibitor, did not show suppression. We also revealed that inhibitors of p38 MAPK and PKC inhibited ATPγS-induced COX-2 mRNA expression. Collectively, purinergic P2Y1 receptor signaling mediates wound-induced COX-2 expression through p38 MAPK and PKC pathways in ISMFs.
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Affiliation(s)
- Koichi Iwanaga
- Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Tokyo 113-8657, Japan
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14
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Santos Cerqueira G, dos Santos e Silva G, Rios Vasconcelos E, Fragoso de Freitas AP, Arcanjo Moura B, Silveira Macedo D, Lopes Souto A, Barbosa Filho JM, de Almeida Leal LK, de Castro Brito GA, Souccar C, de Barros Viana GS. Effects of hecogenin and its possible mechanism of action on experimental models of gastric ulcer in mice. Eur J Pharmacol 2012; 683:260-9. [DOI: 10.1016/j.ejphar.2012.02.043] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2011] [Revised: 02/18/2012] [Accepted: 02/26/2012] [Indexed: 10/28/2022]
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15
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Bridges PJ, Jeoung M, Shim S, Park JY, Lee JE, Sapsford LA, Trudgen K, Ko C, Gye MC, Jo M. Hematopoetic prostaglandin D synthase: an ESR1-dependent oviductal epithelial cell synthase. Endocrinology 2012; 153:1925-35. [PMID: 22374975 PMCID: PMC3320253 DOI: 10.1210/en.2011-1900] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Oviductal disease is a primary cause of infertility, a problem that largely stems from excessive inflammation of this key reproductive organ. Our poor understanding of the mechanisms regulating oviductal inflammation restricts our ability to diagnose, treat, and/or prevent oviductal disease. Using mice, our objective was to determine the spatial localization, regulatory mechanism, and functional attributes of a hypothesized regulator of oviductal inflammation, the hematopoietic form of prostaglandin D synthase (HPGDS). Immunohistochemistry revealed specific localization of HPGDS to the oviduct's epithelium. In the isthmus, expression of HPGDS was consistent. In the ampulla, expression of HPGDS appeared dependent upon stage of the estrous cycle. HPGDS was expressed in the epithelium of immature and cycling mice but not in the oviducts of estrogen receptor α knockouts. Two receptor subtypes bind PGD₂: PGD₂ receptor and G protein-coupled receptor 44. Expression of mRNA for Ptgdr was higher in the epithelial cells (EPI) than in the stroma (P < 0.05), whereas mRNA for Gpr44 was higher in the stroma than epithelium (P < 0.05). Treatment of human oviductal EPI with HQL-79, an inhibitor of HPGDS, decreased cell viability (P < 0.05). Treatment of mice with HQL-79 increased mRNA for chemokine (C-C motif) ligands 3, 4, and 19; chemokine (C-X-C motif) ligands 11 and 12; IL-13 and IL-17B; and TNF receptor superfamily, member 1b (P < 0.02 for each mRNA). Overall, these results suggest that HPGDS may play a role in the regulation of inflammation and EPI health within the oviduct.
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Affiliation(s)
- Phillip J Bridges
- Department of Animal and Food Sciences, University of Kentucky, Lexington, Kentucky 40546, USA.
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16
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Qi Z, Jie L, Haixia C, Xiaoying Z. Effect of rebamipide on quality of peptic ulcer healing in rat. Dig Dis Sci 2009; 54:1876-1883. [PMID: 19082723 DOI: 10.1007/s10620-008-0577-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2008] [Accepted: 10/13/2008] [Indexed: 12/13/2022]
Abstract
The aim of this study is to elucidate the effects and the mechanism of rebamipide, omeprazole, and their combination treatment on quality of peptic ulcer healing (QOUH). Peptic ulcer models were induced by acetic acid exposure of the serosa of rat stomach. Forty Sprague-Dawley (SD) rats were divided randomly into four groups of ten rats each. Saline 2 ml/d (group 1), rebamipide 60 mg/kg/d (group 2), omeprazole 10 mg/kg/d (group 3) as well as its combination regimen (group 4) were administrated for 7 days. After sacrifice, size of the ulcer and focal layer structures were measured in vitro by miniature ultrasonic probe, and the mucosal sections were stained with hematoxylin and eosin (HE) for histological examination; the levels of interleukin (IL)-8/prostaglandin E(2) (PGE(2)) were evaluated by enzyme-linked immunosorbent assay (ELISA) and malondialdehyde (MDA) level was evaluated by thiobarbituric acid (TBA) method. Macroscopically, compared with the control group, the maximal diameters of the ulcers in the medication groups were significantly reduced (P < 0.05), and the layer echo structures of gastric wall were partially rebuilt. Histologically, ulcer range and inflammatory infiltration were less severe compared with the control group. In addition, mucosal MDA and IL-8 levels were significantly decreased, while PGE(2) level was significantly increased in the medication groups. Between the two monotherapy groups, there was no statistical difference in terms of PGE(2) and MDA levels. However, PGE(2) level was significantly increased, while MDA and IL-8 levels were significantly decreased in the combination group. Rebamipide as well as omeprazole and the combination regimen may improve QOUH through increasing the level of PGE(2), decreasing the levels of IL-8 and MDA in gastric mucosa, and this may potentially result in reduced recurrence of ulcer; moreover, the combination regimen was identified as having more antiulcer effects than monotherapy.
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Affiliation(s)
- Zhu Qi
- Department of Gastroenterology, Shanghai Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
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17
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Shahbaz-Samavi M, McKenna F. Nonsteroidal anti-inflammatory drugs. Clin Immunol 2008. [DOI: 10.1016/b978-0-323-04404-2.10088-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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18
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Koon HW, Zhao D, Zhan Y, Rhee SH, Moyer MP, Pothoulakis C. Substance P stimulates cyclooxygenase-2 and prostaglandin E2 expression through JAK-STAT activation in human colonic epithelial cells. THE JOURNAL OF IMMUNOLOGY 2006; 176:5050-9. [PMID: 16585602 PMCID: PMC2593099 DOI: 10.4049/jimmunol.176.8.5050] [Citation(s) in RCA: 84] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Substance P (SP) via its neurokinin-1 receptor (NK-1R) regulates several gastrointestinal functions. We previously reported that NK-1R-mediated chloride secretion in the colon involves formation of PG. PGE2 biosynthesis is controlled by cyclooxygenase-1 (COX-1) and COX-2, whose induction involves the STATs. In this study, we examined whether SP stimulates PGE2 production and COX-2 expression in human nontransformed NCM460 colonocytes stably transfected with the human NK-1R (NCM460-NK-1R cells) and identified the pathways involved in this response. SP exposure time and dose dependently induced an early (1-min) phosphorylation of JAK2, STAT3, and STAT5, followed by COX-2 expression and PGE2 production by 2 h. Pharmacologic experiments showed that PGE2 production is dependent on newly synthesized COX-2, but COX-1 protein. Inhibition of protein kinase Ctheta (PKCtheta), but not PKCepsilon and PKCdelta, significantly reduced SP-induced COX-2 up-regulation, and JAK2, STAT3, and STAT5 phosphorylation. Pharmacological blockade of JAK inhibited SP-induced JAK2, STAT3, and STAT5 phosphorylation; COX-2 expression; and PGE2 production. Transient transfection with JAK2 short-interferring RNA reduced COX-2 promoter activity and JAK2 phosphorylation, while RNA interference of STAT isoforms showed that STAT5 predominantly mediates SP-induced COX-2 promoter activity. Site-directed mutation of STAT binding sites on the COX-2 promoter completely abolished COX-2 promoter activity. Lastly, COX-2 expression was elevated in colon of mice during experimental colitis, and this effect was normalized by administration of the NK-1R antagonist CJ-12,255. Our results demonstrate that SP stimulates COX-2 expression and PGE2 production in human colonocytes via activation of the JAK2-STAT3/5 pathway.
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Affiliation(s)
- Hon-Wai Koon
- Gastrointestinal Neuropeptide Center, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
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19
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Wallace JL, Devchand PR. Emerging roles for cyclooxygenase-2 in gastrointestinal mucosal defense. Br J Pharmacol 2006; 145:275-82. [PMID: 15778736 PMCID: PMC1576151 DOI: 10.1038/sj.bjp.0706201] [Citation(s) in RCA: 115] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
The development of selective inhibitors of cyclooxygenase-2 (COX-2) was based on the concept that this enzyme played little, if any, role in modulating the ability of the gastrointestinal (GI) tract to resist and respond to injury. There is now overwhelming evidence that this is far from true. Indeed, COX-2 mediates several of the most important components of 'mucosal defense', contributes significantly to the resolution of GI inflammation and plays a crucial role in regulating ulcer healing. COX-2 also contributes to long-term changes in GI function after bouts of inflammation.
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Affiliation(s)
- John L Wallace
- Mucosal Inflammation Research Group, University of Calgary, Alberta T2N 4N1, Canada.
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20
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Poonam D, Vinay CS, Gautam P. Cyclo-oxygenase-2 expression and prostaglandin E2 production in experimental chronic gastric ulcer healing. Eur J Pharmacol 2005; 519:277-84. [PMID: 16139265 DOI: 10.1016/j.ejphar.2005.06.055] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2005] [Revised: 06/17/2005] [Accepted: 06/30/2005] [Indexed: 01/08/2023]
Abstract
Prostaglandin, a key molecule that stimulates the complex array of ulcer healing mechanism, gets synthesized in the mucosal cells by cyclooxygenase (COX) enzymes: COX-1 and COX-2. High expression level of COX-2 protein at healing ulcer margins highlights its role in ulcer healing and hypothesized to be an important contributing factor in healing mechanism of anti-ulcer drugs. In the present study we have compared the expression profile of COX-2 protein, prostaglandin E2 (PGE2) levels and myeloperoxidase activity in acetic acid induced chronic gastric ulcer model in rats treated with omeprazole, misoprostol and COX-2 selective nonsteroidal anti-inflammatory drug (NSAID) celecoxib. Both COX-2 expression and PGE2 level have shown differential pattern in different treated groups parallel to the differential effects of these drugs on ulcer healing. Omeprazole has significantly elevated the expression level of COX-2 protein, PGE2 level (19.37%), and decreased myeloperoxidase activity (81.92%), thereby causing the most effective ulcer healing (89.74%). Similar trend was observed with misoprostol, but with relatively less pronounced ulcer healing and COX-2 expression. Celecoxib has retarded COX-2 expression and delayed ulcer healing. Therefore, induction of COX-2 expression leading to higher level of prostaglandin appears to be an important contributing factor in drug mediated ulcer healing apart from the respective mechanisms of different drugs.
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Affiliation(s)
- Dharmani Poonam
- Division of Pharmacology, Central Drug Research Institute, Lucknow-226001, P.B. No. 173, U.P, India
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21
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Abstract
Laparoscopy is a minimally invasive procedure that has applications as a diagnostic, therapeutic and prognostic technique. Specialized equipment is necessary to perform equine laparoscopy, and there is a large range of instruments, both disposable and non-disposable available. Laparoscopic procedures described include ovariectomy, cryptorchidectomy, adhesiolysis and herniorrhaphy. Laparoscopy can be performed in a standing or dorsally recumbent position, depending on surgeon preference, patient status and the procedure to be performed. Stapling equipment is frequently used in gastrointestinal surgery in horses. Advantages include decreased surgical time and a decrease in the risk of contamination. Stapling equipment is often used in creating anastomoses, both in the large and small intestines, as well as in vessel ligation. New surgical techniques intended to decrease adhesion formation include the use of carboxymethylcellulose and bioresorbable patches. Indwelling abdominal drains can be used for peritoneal lavage following surgery and also appear to decrease the risk of adhesion formation. Improvements in post-operative care, including the treatment of post-operative ileus and endotoxaemia can significantly improve the outcome of horses that have undergone surgery for abdominal disorders. Recommendations for the use of prokinetic agents in horses with ileus vary widely. Prokinetic agents include local anaesthetics, macrolide antimicrobials, cholinergic agonists and dopamine antagonists. Endotoxaemia is common in horses following surgery for gastrointestinal disorders. The antibiotic polymyxin B binds to the circulating endotoxin molecule, decreasing its half-life in the intra-vascular space and reducing associated inflammation. This drug appears to be an effective and affordable treatment option for horses with endotoxaemia. The use of specific cyclooxygenase inhibitors in veterinary medicine have been studied recently. Selective cyclooxygenase-2 inhibitors may provide comparable anti-inflammatory and analgesic properties to the non-selective non-steroidal anti-inflammatory drugs. These drugs appear to have similar clinical effectiveness and will hopefully minimize deleterious side effects. The optimal healing of ventral midline incisions in horses is related to many factors including appropriate suture patterns and bite size, in addition to appropriate post-operative exercise recommendations. Recent advances in surgical techniques and post-operative care should decrease the morbidity and mortality associated with abdominal surgery. This article provides an overview of some of these advances.
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Affiliation(s)
- C L Smith
- Faculty of Veterinary Science, University Veterinary Centre, University of Sydney, Werombi Road, New South Wales 2570, Australia
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22
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Lucas R, Warner TD, Vojnovic I, Mitchell JA. Cellular mechanisms of acetaminophen: role of cyclo-oxygenase. FASEB J 2005; 19:635-7. [PMID: 15705740 DOI: 10.1096/fj.04-2437fje] [Citation(s) in RCA: 83] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Acetaminophen is one of the most commonly used drugs for the safe and effective treatment of pain and fever. Acetaminophen works by lowering cyclo-oxygenase products preferentially in the central nervous system, where oxidant stress is strictly limited. However, the precise mechanism of action for acetaminophen on cyclo-oxygenase activity is debated. Two theories prevail. First, it is suggested that acetaminophen selectively inhibits a distinct form of cyclo-oxygenase, cyclo-oxygenase-3. Second, it is suggested that acetaminophen has no affinity for the active site of cyclo-oxygenase but instead blocks activity by reducing the active oxidized form of cyclo-oxygenase to an inactive form. Here, we have used an in vitro model of cyclo-oxygenase-2 activity (A549 cells stimulated with IL-1beta) to show that acetaminophen is an effective inhibitor of cyclo-oxygenase activity in intact cells. However, acetaminophen, unlike nonsteroidal anti-inflammatory drugs (NSAIDs), cannot inhibit activity in broken cell preparations. The inhibitory effects of acetaminophen were abolished by increasing intracellular oxidation conditions with the cell-permeable hydroperoxide t-butylOOH. Similarly the inhibitory effects of the cyclo-oxygenase-2 selective inhibitor rofecoxib or the mixed cyclo-oxygenase-1/cyclo-oxygenase-2 inhibitors ibuprofen and naproxen were significant reduced by t-butylOOH. By contrast, the inhibitory effects of indomethacin or diclofenac, which also inhibit both cyclo-oxygenase-1 and cyclo-oxygenase-2, were unaffected by t-butylOOH. These observations dispel the notion that cyclo-oxygenase-3 is involved in the actions of acetaminophen and provide evidence that supports the theory that acetaminophen interferes with the oxidation state of cyclo-oxygease. Moreover, they suggest for the first time that the inhibitory effects of some NSAIDs, including the newly introduced cyclo-oxygenase-2 selective inhibitor rofecoxib, owe part of their inhibitory actions to effects on oxidation state of cyclo-oxygenase. Our data with t-butylOOH and NSAIDs illustrates an, as yet, undeveloped therapeutic window for the "cyclo-oxygenase inhibitor". Specifically, combining active site selectively with actions on enzyme oxidation state would allow for a broader range of tissue selective drugs.
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Affiliation(s)
- Ruth Lucas
- Cardiothoracic Pharmacology, UCCM, Royal Brompton Hospital, NHLI, Imperial College London, UK
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23
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Motilva V, Alarcón de la Lastra C, Bruseghini L, Manuel Herrerias J, Sánchez-Fidalgo S. COX expression and PGE2 and PGD2 production in experimental acute and chronic gastric lesions. Int Immunopharmacol 2005; 5:369-79. [PMID: 15652766 DOI: 10.1016/j.intimp.2004.10.005] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2004] [Revised: 09/14/2004] [Accepted: 10/15/2004] [Indexed: 10/26/2022]
Abstract
Prostaglandin E(2) and D(2) (PGE(2) and PGD(2)) production and cyclooxygenase-2 (COX-2) expression during the resolution of acute and chronic gastric inflammatory lesions in Wistar rats have been investigated. Differences between ibuprofen, nonselective COX inhibitor, and rofecoxib, specific COX-2 inhibitor, on the development of the induced responses were also analysed. In an acute model, by instillation of HCL, the greatest injury was observed early with a rapid and progressive restoration. Maximal up-regulation of COX-2 protein was detected at 6 h and was accompanied by increase of PGE(2) synthesis but not PGD(2). Both drugs stimulated COX-2 expression in accordance to their capacity of inhibiting this enzymatic activity, driving to delay in the healing. In a chronic model, by acetic acid-induced gastric ulcers, COX-2 was expressed at 7 days and was also associated with PGE(2) increase. Ibuprofen and rofecoxib also augmented COX-2 protein and inhibited PGE(2) levels. However, PGD(2) production was augmented when none signal of COX-2 protein could be detected. Together, this study confirms the role played by COX-2 enzyme in the resolution of acute and chronic gastric inflammatory process, PGE(2) being the principal product. The antiinflammatory effect of nonsteroidal antiinflammatory drugs (NSAIDs) could be mediated not only through the inhibition of COX activity but also through the induction of antiinflammatory PGs production-such as PGD(2)-although further studies would be needed to clarify the mechanisms of this activity and the possible implicated processes.
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Affiliation(s)
- Virginia Motilva
- Department of Pharmacology, Faculty of Pharmacy, University of Seville, Spain.
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