Mitochondrial damage: a possible mechanism of the "topical" phase of NSAID induced injury to the rat intestine.

Abstract:

BACKGROUND:The "topical" effect of non-steroidal anti-inflammatory drugs (NSAIDs) seems to be an important cause of NSAID induced gastrointestinal damage. AIM:To examine the possible mechanism of the "topical" phase of damage in the small intestine. METHODS:Electron microscopy and subcellular organelle marker enzyme studies were done in rat small intestine after oral administration of indomethacin (doses varied between 5 and 30 mg/kg). The effect of conventional and non-acidic NSAIDs on rat liver mitochondrial respiration was measured in vitro in a Clarke-type oxygen electrode. RESULTS:The subcellular organelle marker enzymes showed mitochondrial and brush border involvement within an hour of indomethacin administration. Electron microscopy showed dose dependent mitochondrial changes following indomethacin administration consistent with uncoupling of oxidative phosphorylation (or inhibition of electron transport) which were indistinguishable from those seen with the uncoupler dinitrophenol. Parenteral indomethacin caused similar changes, but not in rats with ligated bile ducts. A range of NSAIDs, but not paracetamol or non-acidic NSAIDs which have a favourable gastrointestinal tolerability profile, uncoupled oxidative phosphorylation in vitro at micromolar concentrations and inhibited respiration at higher concentrations. In vivo studies with nabumetone and aspirin further suggested that uncoupling or inhibition of electron transport underlies the "topical" phase of NSAID induced damage. CONCLUSION:Collectively, these studies suggest that NSAID induced changes in mitochondrial energy production may be an important component of the "topical" phase of damage induction.

journal_name

Gut

journal_title

Gut

authors

Somasundaram S,Rafi S,Hayllar J,Sigthorsson G,Jacob M,Price AB,Macpherson A,Mahmod T,Scott D,Wrigglesworth JM,Bjarnason I

doi

10.1136/gut.41.3.344

subject

Has Abstract

pub_date

1997-09-01 00:00:00

pages

344-53

issue

3

eissn

0017-5749

issn

1468-3288

journal_volume

41

pub_type

杂志文章

相关文献

GUT文献大全
  • Young-onset colorectal cancer risk among individuals with iron-deficiency anaemia and haematochezia.

    abstract:OBJECTIVE:Young-onset colorectal cancer (YCRC) incidence is rising. Scant data exist on YCRC risk after presentation with concerning symptoms such as iron-deficiency anaemia (IDA) or haematochezia. We examined the association between IDA and YCRC, and haematochezia and YCRC. DESIGN:Cohort study of US Veterans aged 18-...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gutjnl-2020-321849

    authors: Demb J,Liu L,Murphy CC,Doubeni CA,Martínez ME,Gupta S

    更新日期:2020-12-18 00:00:00

  • Inhibition of nocturnal acidity is important but not essential for duodenal ulcer healing.

    abstract::We have determined the relative importance of day and night time gastric acid inhibition for duodenal ulcer healing by comparing the anti-ulcer efficacy of a single morning with that of a single bedtime dose of ranitidine. One hundred and thirty patients with active duodenal ulcer were randomly assigned to a double-bl...

    journal_title:Gut

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1136/gut.31.4.397

    authors: Bianchi Porro G,Parente F,Sangaletti O

    更新日期:1990-04-01 00:00:00

  • Faecal immunochemical tests versus guaiac faecal occult blood tests: what clinicians and colorectal cancer screening programme organisers need to know.

    abstract::Although colorectal cancer (CRC) is a common cause of cancer-related death, it is fortunately amenable to screening with faecal tests for occult blood and endoscopic tests. Despite the evidence for the efficacy of guaiac-based faecal occult blood tests (gFOBT), they have not been popular with primary care providers in...

    journal_title:Gut

    pub_type: 杂志文章,评审

    doi:10.1136/gutjnl-2014-308074

    authors: Tinmouth J,Lansdorp-Vogelaar I,Allison JE

    更新日期:2015-08-01 00:00:00

  • Early gastric cancer in Europe.

    abstract::Despite mass population screening and an incidence of EGC in Japan that is at least double that of the West, there seem to be no genuine differences in the clinicopathological features of the disease between the two regions. The macroscopic appearance, size, depth of invasion, frequency of lymph node invasion, and his...

    journal_title:Gut

    pub_type: 杂志文章,评审

    doi:10.1136/gut.41.2.142

    authors: Everett SM,Axon AT

    更新日期:1997-08-01 00:00:00

  • Effect of Helicobacter pylori eradication on development of dyspeptic and reflux disease in healthy asymptomatic subjects.

    abstract:BACKGROUND AND AIM:There are few data on the course of Helicobacter pylori infection in asymptomatic subjects. The aim of this study was to assess the effect of eradication therapy on the development of dyspeptic and gastro-oesophageal reflux disease in a cohort of asymptomatic individuals observed over a prolonged per...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.52.11.1543

    authors: Vaira D,Vakil N,Rugge M,Gatta L,Ricci C,Menegatti M,Leandro G,Holton J,Russo VM,Miglioli M

    更新日期:2003-11-01 00:00:00

  • Interferon alfa-2b for decompensated liver disease caused by either chronic hepatitis B or C: preliminary results of a pilot study.

    abstract::This pilot study was designed to assess the tolerance and effectiveness of interferon alfa-2b in patients with decompensated liver disease caused by chronic hepatitis B (n = 7) or C (n = 5). Preliminary results suggest that patients may benefit from small doses of interferon (improvement in liver function tests and re...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.34.2_suppl.s104

    authors: Dimopoulou M,Fafoutis K,Basiliou K,Ketikoglou J,Karvountzis G

    更新日期:1993-01-01 00:00:00

  • Gut microbiome analysis as a tool towards targeted non-invasive biomarkers for early hepatocellular carcinoma.

    abstract:OBJECTIVE:To characterise gut microbiome in patients with hepatocellular carcinoma (HCC) and evaluate the potential of microbiome as non-invasive biomarkers for HCC. DESIGN:We collected 486 faecal samples from East China, Central China and Northwest China prospectively and finally 419 samples completed Miseq sequencin...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gutjnl-2017-315084

    authors: Ren Z,Li A,Jiang J,Zhou L,Yu Z,Lu H,Xie H,Chen X,Shao L,Zhang R,Xu S,Zhang H,Cui G,Chen X,Sun R,Wen H,Lerut JP,Kan Q,Li L,Zheng S

    更新日期:2019-06-01 00:00:00

  • Gastric B-cell mucosa associated lymphoid tissue lymphoma: a clinicopathological study in 56 patients.

    abstract::Clinico-pathological features of 56 patients with primary gastric lymphoma were evaluated retrospectively. All cases were regraded according to a classification of Isaacson et al into high grade and low grade B-cell mucosa associated lymphoid tissue lymphoma. A third group of mixed grade was recognised in 11 patients ...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.33.10.1307

    authors: Castrillo JM,Montalban C,Obeso G,Piris MA,Rivas MC

    更新日期:1992-10-01 00:00:00

  • Cancer surveillance in longstanding ulcerative colitis: endoscopic appearances help predict cancer risk.

    abstract:BACKGROUND AND AIMS:The risk of colorectal cancer is increased in ulcerative colitis (UC). Patients with UC have diverse colonoscopic appearances. Determining colonoscopic markers for cancer risk could allow patient risk stratification. PATIENTS AND METHODS:Following on from an earlier study which demonstrated a corre...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.2003.038505

    authors: Rutter MD,Saunders BP,Wilkinson KH,Rumbles S,Schofield G,Kamm MA,Williams CB,Price AB,Talbot IC,Forbes A

    更新日期:2004-12-01 00:00:00

  • Effect of ICS 205-930 (a specific 5-HT3 receptor antagonist) on gastric emptying of a solid meal in normal subjects.

    abstract::The effects on gastric emptying of a solid meal of the specific 5-HT3-receptor antagonist ICS 205-930, 10 mg and 20 mg intravenously were assessed with a scintigraphic technique in 12 normals. The 50% emptying time was less, the lag phase was shorter and the post lag emptying rate was faster after 20 mg ICS 205-930 (p...

    journal_title:Gut

    pub_type: 临床试验,杂志文章

    doi:10.1136/gut.29.9.1249

    authors: Akkermans LM,Vos A,Hoekstra A,Roelofs JM,Horowitz M

    更新日期:1988-09-01 00:00:00

  • Treatment of bone loss in osteopenic patients with Crohn's disease: a double-blind, randomised trial of oral risedronate 35 mg once weekly or placebo, concomitant with calcium and vitamin D supplementation.

    abstract:OBJECTIVE:Osteoporosis and fractures are frequently encountered in patients with Crohn's disease. In order to prevent fractures, treatment with bone protecting drugs appears warranted early in the course of bone disease when bone loss is not yet prominent. We therefore aimed to demonstrate a beneficial effect on bone d...

    journal_title:Gut

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1136/gutjnl-2013-305523

    authors: van Bodegraven AA,Bravenboer N,Witte BI,Dijkstra G,van der Woude CJ,Stokkers PC,Russel MG,Oldenburg B,Pierik M,Roos JC,van Hogezand RA,Dik VK,Oostlander AE,Netelenbos JC,van de Langerijt L,Hommes DW,Lips P,Dutch Initiat

    更新日期:2014-09-01 00:00:00

  • Clinical presentation, diagnosis and long-term outcome of Wilson's disease: a cohort study.

    abstract:BACKGROUND:Wilson's disease is a rare inborn disease related to copper storage, leading to liver cirrhosis and neuropsychological deterioration. Clinical data on larger cohorts are limited owing to low disease frequency. OBJECTIVE AND METHODS:We performed a retrospective analysis of 163 patients with Wilson's disease,...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.2005.087262

    authors: Merle U,Schaefer M,Ferenci P,Stremmel W

    更新日期:2007-01-01 00:00:00

  • Predictive value of oesophageal pH variables in children with gastro-oesophageal reflux.

    abstract::Sixty three 24 hour oesophageal pH studies were performed in children with known or suspected gastro-oesophageal reflux and their progress was followed for at least a year. Forty two studies were of children who were well at follow up who were not receiving medical treatment for gastro-oesophageal reflux, and had not ...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.31.4.370

    authors: Colson DJ,Campbell CA,Wright VA,Watson BW

    更新日期:1990-04-01 00:00:00

  • Optimum bile acid treatment for rapid gall stone dissolution.

    abstract::To determine the optimum bile acid regimen for rapid gall stone dissolution, 48 gall stone patients were divided into four groups of 12 according to stone diameter and were randomly allocated to receive one of four treatment regimens: bedtime or mealtime chenodeoxycholic acid (CDCA, 12 mg/kg/day) and bedtime or mealti...

    journal_title:Gut

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1136/gut.33.3.381

    authors: Jazrawi RP,Pigozzi MG,Galatola G,Lanzini A,Northfield TC

    更新日期:1992-03-01 00:00:00

  • Long-term performance of colorectal cancerscreening programmes based on the faecal immunochemical test.

    abstract:BACKGROUND:The long-term performance of colorectal cancer (CRC) screening programmes based on a 2-year faecal immunochemical test (FIT) is still unclear. METHODS:In a sample of 50 to 69-year-olds repeatedly screened with the FIT (OC-Hemodia latex agglutination test; cut-off: 20 µg haemoglobin/g faeces), we examined: (...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gutjnl-2017-314753

    authors: Zorzi M,Hassan C,Capodaglio G,Fedato C,Montaguti A,Turrin A,Rosano A,Monetti D,Stocco C,Baracco S,Russo F,Repici A,Rugge M

    更新日期:2018-12-01 00:00:00

  • Papaverine stimulation of prostaglandin E2 production by cultured rabbit gastric mucosa.

    abstract::Prostaglandins (PGs) are synthesised by gastric mucosa, and have been shown to inhibit gastric acid secretion and ulcer formation in man and experimental animals. Recently exogenous PGs, mainly of the E group, have been used for the treatment of peptic ulcer disease. We therefore searched for a drug that would stimula...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.20.10.882

    authors: Ligumsky M,Rachmilewitz D,Zor U

    更新日期:1979-10-01 00:00:00

  • A monoclonal anti-interleukin 8 antibody (WS-4) inhibits cytokine response and acute lung injury in experimental severe acute necrotising pancreatitis in rabbits.

    abstract:BACKGROUND:Interleukin 8 (IL-8) has recently been proposed to have an important role in mediating the development of the systemic sequelae associated with severe acute pancreatitis. AIMS:To define the role of IL-8 in acute pancreatitis by neutralising its effects with a monoclonal anti-IL-8 antibody (WS-4), in a rabbi...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.43.2.232

    authors: Osman MO,Kristensen JU,Jacobsen NO,Lausten SB,Deleuran B,Deleuran M,Gesser B,Matsushima K,Larsen CG,Jensen SL

    更新日期:1998-08-01 00:00:00

  • Gastroparesis: separate entity or just a part of dyspepsia?

    abstract::Gastroparesis is defined by the presence of delayed gastric emptying (GE) in the absence of mechanical obstruction. Symptoms that have been attributed to gastroparesis include postprandial fullness, early satiation nausea and vomiting. Gastroprokinetic drugs are the preferred treatment option. A number of problems wit...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gutjnl-2013-306084

    authors: Stanghellini V,Tack J

    更新日期:2014-12-01 00:00:00

  • Improving the selection of patients for upper gastrointestinal endoscopy.

    abstract::A retrospective study was undertaken to investigate how endoscopies yielding positive findings differ a priori from those yielding negative findings: and how those judged 'helpful' (in the sense of influencing management) differ a priori from those judged 'unhelpful'. A total of 483 patients undergoing endoscopy was s...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.34.2.187

    authors: Naji SA,Brunt PW,Hagen S,Mowat NA,Russell IT,Sinclair TS,Tang TM

    更新日期:1993-02-01 00:00:00

  • Periampullary cyst: a surgically remediable cause of pancreatitis.

    abstract::We report two patients with periampullary cysts associated with recurrent attacks of acute pancreatitis. In both patients the diagnosis was made preoperatively by upper gastrointestinal endoscopy and ERCP, which was also useful in determining the relationship of the cysts to the biliary and pancreatic ductal systems. ...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.28.3.358

    authors: Kalvaria I,Bornman PC,Girdwood AH,Marks IN

    更新日期:1987-03-01 00:00:00

  • Coeliac disease in the father affects the newborn.

    abstract:BACKGROUND AND AIMS:Untreated coeliac disease in the mother is associated with lower birth weight. We examined the risk of adverse neonatal outcome when the infant's mother, father, or other relative suffered from known coeliac disease. METHODS:Mothers answered a questionnaire a few days after the birth of their infan...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.49.2.169

    authors: Ludvigsson JF,Ludvigsson J

    更新日期:2001-08-01 00:00:00

  • Leadership training to improve adenoma detection rate in screening colonoscopy: a randomised trial.

    abstract:OBJECTIVE:Suboptimal adenoma detection rate (ADR) at colonoscopy is associated with increased risk of interval colorectal cancer. It is uncertain how ADR might be improved. We compared the effect of leadership training versus feedback only on colonoscopy quality in a countrywide randomised trial. DESIGN:40 colonoscopy...

    journal_title:Gut

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1136/gutjnl-2014-307503

    authors: Kaminski MF,Anderson J,Valori R,Kraszewska E,Rupinski M,Pachlewski J,Wronska E,Bretthauer M,Thomas-Gibson S,Kuipers EJ,Regula J

    更新日期:2016-04-01 00:00:00

  • Effect of anticoagulants and NSAIDs on accuracy of faecal immunochemical tests (FITs) in colorectal cancer screening: a systematic review and meta-analysis.

    abstract:OBJECTIVE:Most colorectal cancer (CRC) screening programmes are nowadays based on faecal immunochemical testing (FIT). Eligible subjects often use oral anticoagulants (OACs) or non-steroidal anti-inflammatory drugs (NSAIDs), which could possibly stimulate bleeding from both benign and premalignant lesions in the colon....

    journal_title:Gut

    pub_type: 杂志文章,meta分析

    doi:10.1136/gutjnl-2018-316344

    authors: Nieuwenburg SAV,Vuik FER,Kruip MJHA,Kuipers EJ,Spaander MCW

    更新日期:2019-05-01 00:00:00

  • Dual prognostic significance of tumour-associated macrophages in human pancreatic adenocarcinoma treated or untreated with chemotherapy.

    abstract:OBJECTIVE:Tumour-associated macrophages (TAMs) play key roles in tumour progression. Recent evidence suggests that TAMs critically modulate the efficacy of anticancer therapies, raising the prospect of their targeting in human cancer. DESIGN:In a large retrospective cohort study involving 110 patients with pancreatic ...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gutjnl-2015-309193

    authors: Di Caro G,Cortese N,Castino GF,Grizzi F,Gavazzi F,Ridolfi C,Capretti G,Mineri R,Todoric J,Zerbi A,Allavena P,Mantovani A,Marchesi F

    更新日期:2016-10-01 00:00:00

  • Spirochaetosis of the human rectum associated with an intraepithelial mast cell and IgE plasma cell response.

    abstract::In two patients presenting with mild intestinal symptoms, rectal spirochaetosis was the only morphological abnormality diagnosed by light microscopy. A re-evaluation of the morphological changes using electron microscopy and immunohistochemistry showed certain unusual features: the microorganisms were observed within ...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.28.5.588

    authors: Gebbers JO,Ferguson DJ,Mason C,Kelly P,Jewell DP

    更新日期:1987-05-01 00:00:00

  • Reduced mucosal antimicrobial activity in Crohn's disease of the colon.

    abstract:OBJECTIVES:In order to maintain the mucosal barrier against luminal microorganisms the intestinal epithelial cells synthesise various broad-spectrum antimicrobial peptides including defensins and cathelicidins. Recent studies indicate that both may be deficient in Crohn's disease. To elucidate the possible functional c...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.2006.118646

    authors: Nuding S,Fellermann K,Wehkamp J,Stange EF

    更新日期:2007-09-01 00:00:00

  • Psychological treatments of the irritable bowel syndrome: a review.

    abstract::Psychological treatments are increasingly being used to help patients with the irritable bowel syndrome (IBS), but the efficacy of such treatments is still debated. This review indicates that there are three ways in which they might have been effective in published studies to date; relating bowel symptoms to stress, s...

    journal_title:Gut

    pub_type: 杂志文章,评审

    doi:10.1136/gut.30.11.1601

    authors: Creed F,Guthrie E

    更新日期:1989-11-01 00:00:00

  • Prednisolone absorption in acute colitis.

    abstract::Peak plasma levels were reduced after an oral dose of 40 mg prednisolone in six patients with severe acute colitis as compared with six normal subjects, though total absorption appeared to be similar; the findings suggest that prednisolone absorption was delayed in acute colitis. A dilutional fall in plasma albumin wa...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.21.1.49

    authors: Elliott PR,Powell-Tuck J,Gillespie PE,Laidlow JM,Lennard-Jones JE,English J,Chakraborty J,Marks V

    更新日期:1980-01-01 00:00:00

  • Plasminogen fragment K1-5 improves survival in a murine hepatocellular carcinoma model.

    abstract:BACKGROUND:The prognosis of patients with hepatocellular carcinoma (HCC) remains poor, and new alternative treatments are needed. AIMS:To comparatively test the angiostatic and antitumour effects of adenoviral gene transfer of angiostatin (PlgK1-4, amino acids 1-440) and full kringles 1-5 (PlgK1-5, amino acids 1-546) ...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.2005.088583

    authors: Schmitz V,Raskopf E,Gonzalez-Carmona MA,Vogt A,Rabe C,Leifeld L,Kornek M,Sauerbruch T,Caselmann WH

    更新日期:2007-02-01 00:00:00

  • General and cancer specific mortality of a population based cohort of patients with inflammatory bowel disease: the Florence Study.

    abstract:BACKGROUND:A population based epidemiological study identified all the patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) resident in the Florence area in the period 1978-1992. AIMS:To assess the mortality of unselected patients with inflammatory bowel disease (IBD) in a Mediterranean country. ME...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.42.2.175

    authors: Palli D,Trallori G,Saieva C,Tarantino O,Edili E,D'Albasio G,Pacini F,Masala G

    更新日期:1998-02-01 00:00:00