Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038358 (gastric ulcer)
 5,179 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Matrix metalloproteinases (MMPs) play an important role in degradation of gastric extracellular matrix proteins. However, no reports are available on the relationship between the activity of MMPs and gastric ulceration induced by alcohol. Our objective was to investigate the effect of melatonin (N-acetyl-5-methoxytryptamine) on the regulation of MMP-9 and MMP-2 activities during prevention of ethanol-induced gastric ulcer. Biochemical and zymographic methods were used to analyze MMP-9 and -2 activities in gastric tissues of Balb/c mice following induction of gastric ulcer by ethanol. Our studies reveal that melatonin arrested cell injury, protein carbonyl formation, and lipid peroxidation in mice during gastroprotection. Melatonin dose-dependently reduced proMMP-9 activity that was induced ( approximately 25-fold) during ethanol-induced gastric ulceration. Severity of gastric ulcers were correlated proportionately with increased dose of ethanol and elevated activity of proMMP-9 and -2. The reduced activities of MMP-9 and -2 were associated with reduced expression of TNF-alpha and increased expression of tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2). We conclude that melatonin's ability to prevent ethanol-induced gastric ulceration in mice is related to a reduction in proMMP-9 activity and expression.
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PMID:Matrix metalloproteinase-9 activity and expression is reduced by melatonin during prevention of ethanol-induced gastric ulcer in mice. 1761 36

Hormonal fluctuations are known to predispose ulceration of the upper gastrointestinal tract, but to date no comparative study of their effects on the healing of pre-existing ulcers in the oral cavity and stomach has been made. We studied the effects of depletion of testosterone and of EGF on the healing of acetic acid-induced ulcers using rats having undergone bilateral orchidectomy and/or salivectomy respectively. We measured alterations in gastric acid secretion and blood flow at ulcer margins, as well as plasma levels of testosterone, gastrin and the proinflammatory cytokines IL-1 beta and TNF-alpha. Testosterone (0.01-10 mg/kg/day i. m.) dose-dependently delayed oral and gastric ulcer healing. When applied in an optimal dose of 1 mg/kg/day, this hormone significantly raised gastric acid secretion and plasma IL-1 beta and TNF-alpha levels. Attenuation of plasma testosterone levels via bilateral orchidectomy inhibited gastric acid secretion and accelerated the healing of oral and gastric ulcers, while increasing plasma gastrin levels and these effects were reversed by testosterone. Salivectomy raised plasma testosterone levels, and delayed oral and gastric ulcer healing. Treatment of salivectomised animals with testosterone further inhibited ulcer healing, and this effect was counteracted by EGF. We propose that testosterone delays ulcer healing via a fall in blood flow at the ulcer margin, a rise in plasma levels of IL-1 beta and TNF-alpha and, in the case of gastric ulcers, an increase in gastric acid secretion. EGF released from the salivary glands plays an important role in limitation of the deleterious effects of testosterone on ulcer healing.
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PMID:Gastric secretion, proinflammatory cytokines and epidermal growth factor (EGF) in the delayed healing of lingual and gastric ulcerations by testosterone. 1804 13

Evidences suggest Peroxisome Proliferator Activated Receptor-gamma (PPAR-gamma) ligand, pioglitazone results in the attenuation of gastric mucosal injury. But the molecular mechanism through which these agonists actually elicit gastroprotection through modulating inflammatory responses has not yet been established. Chronic gastric ulcer induced in rats by intraluminal application of acetic acid resulted in elevation of proinflammatory cytokines gene expression, such as, TNF-alpha (Tumor Necrosis Factor-alpha), IL-1beta (Interleukin-1beta) and the protein levels of nuclear p65 subunit of NF-kappaB (Nuclear Factor-kappaB) but decreased levels of PPAR-gamma gene expression. Pioglitazone treatment reduced the severity of ulceration, repressed levels of TNF-alpha, IL-1beta and nuclear p65 subunit as well as increased the abundance of PPAR-gamma in gastric mucosa. Moreover, it significantly upregulated protein levels of glucocorticoid receptor demonstrating its possible involvement in pioglitazone mediated ulcer healing along with PPAR-gamma. Administration of pioglitazone reverted back the decreased levels of both PPAR-gamma and glucocorticoid receptor, resulting in their redistribution to the nucleus from the cytosol in course of ulcer healing. Moreover, pharmacological inhibition of glucocorticoid receptor function by its antagonist (RU486) inhibited pioglitazone mediated downregulation of TNF-alpha and IL-1beta gene expression confirming involvement of glucocorticoid receptor in pioglitazone mediated ulcer healing. Co-immunoprecipitation studies further established association of PPAR-gamma with glucocorticoid receptor during ulcer healing which was enhanced following pioglitazone administration. Thus, the present study is first of its kind bearing direct relevance to the participation of both PPAR-gamma and glucocorticoid receptor and their physical association in influencing amelioration of inflammatory responses during pioglitazone mediated gastric ulcer healing.
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PMID:Involvement of glucocorticoid receptor and peroxisome proliferator activated receptor-gamma in pioglitazone mediated chronic gastric ulcer healing in rats. 1928 8

The pathogenesis of gastric ulcer is associated with remodeling of extracellular matrix (ECM) by various matrix metalloproteinases (MMPs). However, how MMPs are regulated during nonsteroidal anti-inflammatory drug (NSAID)-induced acute gastric ulceration is not well studied. In this study, different NSAIDs (80 mg/kg b.w.) were applied to generate acute gastric ulcer in the BALB/c mouse and the regulation of MMPs were investigated. NSAIDs caused dose-dependent induction in MMP-9 and -3 activities and expressions in ulcerated gastric tissues along with significant infiltration of inflammatory cells and disruption of gastric mucosal layer. In addition, an increase in tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-8 expression, excessive generation of hydroxyl radical ((*)OH), and protein oxidation and lipid peroxidation were observed in acute ulcerated gastric tissues. In this study, the efficacy of melatonin on activities of MMP-9 and -3 during prevention of gastric ulcers was tested. Melatonin at a dose of 60 mg/kg b.w. downregulated MMP-9 and -3 both at the enzyme and protein levels in mouse gastric tissues during prevention as well as healing of acute gastric ulcers. It also blocked oxidative stress via inhibition of protein oxidation, lipid peroxidation, (*)OH generation and SOD-2 expression. Moreover, it suppressed myeloperoxidase activity and expressions of TNF-alpha, IL-1beta and IL-8. This study documents for the first time that induction of MMP-9 and -3 activities accompany NSAID-induced inflammation and oxidative stress in gastric tissues and indicates that, melatonin may be a preventive or therapeutic remedy for gastric ulcers.
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PMID:Induction of matrix metalloproteinase-9 and -3 in nonsteroidal anti-inflammatory drug-induced acute gastric ulcers in mice: regulation by melatonin. 1952 38

The effect of tacrolimus (FK506) on peptic ulcer was evaluated using pyloric ligation (PL) model in rats. Tacrolimus was administered orally at different doses (1, 2 and 3 mg/kg) and it showed a gastric ulcer healing effect in a dose dependent manner. Gastric volume, total and free acidity and ulcerative index parameters were reduced in the tacrolimus treated rats as compared to pyloric ligated rats. The higher dose (3 mg/kg) treated group produced significant results similar to that of the ranitidine (50 mg/kg) treated group. Pretreatment with tacrolimus also produced significant (p<0.05) reduction in TBARS, total calcium, TNF-alpha, IL-8 and MPO whereas it showed an increase in GSH level at higher dose. The anti-secretory and anti-ulcerative effect of tacrolimus may be due to immunosuppressive actions by inhibition of calcineurin and the oxidative pathway. It can be concluded that tacrolimus can play an important role in the treatment of peptic ulcer disorder to improve the quality of life.
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PMID:Activity of tacrolimus: an immunosuppressant, in pyloric ligation-induced peptic ulcer in the rat. 1995 32

In recent years, gastric ulceration has been recognized as a common, possibly performance-limiting disease, of adult horses. The aim of this study was to compare endoscopic features, histological diagnosis, and mRNA levels of various cytokines (TNF-alpha, IL-1beta, and IL-13) from horse gastric biopsies. Eleven horses suffering from equine gastric ulcer syndrome and seven horses with normal histological gastric features were assessed. No correlation between endoscopic features and histology (i.e., the gold standard) was observed. Based on histological diagnosis, a significant (p < 0.05) increase in cytokine mRNA levels (specifically, TNF-alpha and IL-13) was observed in horses affected by equine ulcerative gastric syndrome.
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PMID:Comparison of endoscopy, histology, and cytokine mRNA of the equine gastric mucosa. 2047 66

Intestinal subepithelial myofibroblasts play crucial role in the growth and development of the intestine. Colitis, small bowel injury, gastric ulcer disease and inflammatory bowel disease (IBD) accompany the increase of number of activated myofibroblasts. In the last few years, the increasing production of electromagnetic (EMF) and static magnetic fields (SMF), due to the expanding use of electronic devices in everyday life, has led to a number of studies on the effects of these fields on living organisms. EMF therapy, because of its anti-inflammatory properties, may be used in medicine in IBD treatment. This mechanism has not been elucidated yet. In the present work normal human colon myofibroblasts CCD-18Co were exposed to SMF with a flux density of 300 mT. After 24 h incubation TNF-alpha-dependent IL-6 secretion was determined with ELISA kit (RandD Systems).The influence of magnetic field and its effect on cell proliferation were determined with TOX-2 (In Vitro Toxicology Assay Kit XTT Based, TOX-2, Sigma) and CyQUANT NF cell proliferation assay kit (Molecular Probes). It was shown that SMF inhibited TNF-alpha-dependent IL-6 secretion. The observed effects were statistically significant and depended on the time of incubation. Moreover, SMF triggered cell proliferation whereas it did not alter cell viability. IL-6 belongs to pro-inflammatory cytokines family and plays a crucial role in IBD. Inhibition of IL-6 secretion by SMF and lack of its cytotoxic effect seem to be advantageous whilst SMF is implicated in the treatment of inflammatory diseases associated by increase in number of activated myofibroblasts.
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PMID:Effects of 300 mT static magnetic field on IL-6 secretion in normal human colon myofibroblasts. 2328 97


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