Involvement of reactive oxygen species in indomethacin-induced apoptosis of small intestinal epithelial cells.


BACKGROUND:The precise pathogenic mechanism of nonsteroidal antiinflammatory drug-induced small intestinal injury is still unknown. In the present study, we investigated the mechanism by which indomethacin induced mucosal injury by using an in vitro model of small intestine. METHODS:The colon cancer cell line Caco-2, exhibiting a small intestinal phenotype starting as a crypt cell and differentiating to a villous phenotype, and RIE, a rat intestinal epithelial cell line, were employed. Indomethacin was added to differentiated the Caco-2 and RIE monolayer, and cell death was quantified by MTT assay and LDH release in the cell culture supernatant. Indomethacin-induced cell death was also qualified by fluorescent probes under the fluorescent microscope. As a functional study, the permeability of the Caco-2 monolayer was assessed by measuring transepithelial electrical resistance (TEER) and the flux of FITC-conjugated dextran across the monolayer. Indomethacin-induced reactive oxygen species production in Caco-2 and RIE was evaluated by redoxsensitive fluorogenic probes using a fluorometer. In some experiments, antioxidants were used to clarify the role of reactive oxygen species on indomethacin-induced Caco-2 cell death. RESULTS:Indomethacin caused cell death (mainly apoptosis) of Caco-2 and RIE in a dose-and time-dependent manner that was correlated with increased permeability of the Caco-2 monolayer. Exposure of Caco-2 and RIE with indomethacin also resulted in a significant reactive oxygen species production that was inhibited by the pretreatment of these cells with antioxidants. CONCLUSIONS:Taken together, reactive oxygen species production is one of the mechanisms by which indomethacin induced small intestinal injury.


J Gastroenterol


Omatsu T,Naito Y,Handa O,Hayashi N,Mizushima K,Qin Y,Hirata I,Adachi S,Okayama T,Kishimoto E,Takagi T,Kokura S,Ichikawa H,Yoshikawa T




Has Abstract


2009-01-01 00:00:00








44 Suppl 19


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    authors: Toyama N,Kamiyama H,Suminaga Y,Namai K,Ota M,Konishi F

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    abstract:BACKGROUND:The levels of serum HER2 extracellular domain (ECD) are highly correlated with tissue HER2 status in metastatic gastric cancer (AGC). We sought to explore whether serum HER2 ECD could predict the efficacy of trastuzumab-treated HER2-positive AGC. MATERIALS AND METHODS:From 2011 to 2013, trastuzumab-treated ...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Zhou J,Peng Z,Liu Y,Gong J,Zhang X,Lu M,Gao J,Li Y,Li Y,Shen L

    更新日期:2015-09-01 00:00:00

  • A new prognostic formula for adult acute liver failure using computer tomography-derived hepatic volumetric analysis.

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    authors: Yamagishi Y,Saito H,Ebinuma H,Kikuchi M,Ojiro K,Kanamori H,Tada S,Horie Y,Kato S,Hibi T

    更新日期:2009-01-01 00:00:00

  • Significance of modes of adherence in esophageal Candida albicans.

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    pub_type: 杂志文章


    authors: Hoshika K,Mine H

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  • Nationwide epidemiological survey of autoimmune pancreatitis in Japan in 2016.

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  • Does gastroesophageal reflux have an influence on bleeding from esophageal varices?

    abstract:BACKGROUND:Mucosal breaks induced by gastroesophageal reflux of gastric contents were more frequently found on the right anterior wall of the lower esophagus. Bleeding from esophageal varices may be also derived from gastroesophageal reflux. The circumferential location of the ruptured esophageal varices was evaluated ...

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    authors: Okamoto E,Amano Y,Fukuhara H,Furuta K,Miyake T,Sato S,Ishihara S,Kinoshita Y

    更新日期:2008-01-01 00:00:00

  • Intestine-specific homeobox (ISX) induces intestinal metaplasia and cell proliferation to contribute to gastric carcinogenesis.

    abstract:BACKGROUND:Helicobacter pylori induces chronic inflammation and intestinal metaplasia (IM) through genetic and epigenetic changes and activation of intracellular signaling pathways that contribute to gastric carcinogenesis. However, the precise mechanism of IM in gastric carcinogenesis has not been fully elucidated. We...

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    pub_type: 杂志文章


    authors: Sue S,Shibata W,Kameta E,Sato T,Ishii Y,Kaneko H,Miwa H,Sasaki T,Tamura T,Kondo M,Maeda S

    更新日期:2016-10-01 00:00:00

  • Impairment of chemical clearance and mucosal integrity distinguishes hypersensitive esophagus from functional heartburn.

    abstract:BACKGROUND:Hypersensitive esophagus (HE) is defined by endoscopy-negative heartburn with a normal acid exposure time but positive symptom association probability (SAP) and/or symptom index (SI) on impedance-pH monitoring, and proton pump inhibitor (PPI) responsiveness. Functional heartburn (FH) is distinguished by nega...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章,多中心研究


    authors: Frazzoni M,de Bortoli N,Frazzoni L,Furnari M,Martinucci I,Tolone S,Farioli A,Marchi S,Fuccio L,Savarino V,Savarino E

    更新日期:2017-04-01 00:00:00

  • An experimental study of gastric mucosal blood flow in endotoxemia of the rat, with special reference to the vagus nerve and EDRF.

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    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Sakano T,Itoh K,Tanaka M,Arakawa Y,Matsuo Y

    更新日期:1995-02-01 00:00:00

  • Is genetic analysis helpful for diagnosing chronic pancreatitis in its early stage?

    abstract::Diagnosis of chronic pancreatitis in its early stage is an extremely difficult task. If the genetic predispositions are identified, it may help make possible the earlier diagnosis of chronic pancreatitis or the detection of patients at risk. There are two major hypotheses about the pathogenesis of chronic pancreatitis...

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    pub_type: 杂志文章,评审


    authors: Naruse S,Fujiki K,Ishiguro H

    更新日期:2007-01-01 00:00:00

  • Circular RNA TMEM87A promotes cell proliferation and metastasis of gastric cancer by elevating ULK1 via sponging miR-142-5p.

    abstract:BACKGROUND:Circular RNAs (circRNAs) act as vital regulators of gene expression in a variety of cancers. However, the role of circRNAs in gastric cancer (GC) remains largely unexplored. Herein, we identified that circTMEM87A sponges miR-142-5p to promote GC progression through up-regulating ULK1 expression. METHODS:The...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Wang H,Sun G,Xu P,Lv J,Zhang X,Zhang L,Wang S,Cao J,Xia Y,Xuan Z,Li B,Huang X,Jiang T,Fang L,Xu Z

    更新日期:2020-11-06 00:00:00

  • Treatment of bleeding stomal varices by balloon-occluded retrograde transvenous obliteration.

    abstract::Although stomal varices are a rare complication, bleeding stomal varices often need to be treated owing to symptoms of hypovolemic shock, recurrence of stomal bleeding, or deterioration in the quality of life. Various treatment strategies for the management of bleeding stomal varices have thus far been reported. We re...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Minami S,Okada K,Matsuo M,Kamohara Y,Sakamoto I,Kanematsu T

    更新日期:2007-01-01 00:00:00

  • Inhibition of neutrophil elastase prevents the development of murine dextran sulfate sodium-induced colitis.

    abstract:BACKGROUND:Neutrophil elastase (NE) is a major secretory product from activated neutrophils and a major contributor to tissue destruction. However, little is known about the pathogenic contribution of NE to ulcerative colitis (UC). This study was designed to investigate the contribution of NE by measuring NE activity i...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Morohoshi Y,Matsuoka K,Chinen H,Kamada N,Sato T,Hisamatsu T,Okamoto S,Inoue N,Takaishi H,Ogata H,Iwao Y,Hibi T

    更新日期:2006-04-01 00:00:00

  • Sex differences in relation to serum hepatitis B e antigen and alanine aminotransferase levels among asymptomatic hepatitis B surface antigen carriers.

    abstract::This study aimed to investigate sex differences in relation to hepatitis B e antigen (HBeAg) and serum alanine aminotransferase (ALT) levels in chronic asymptomatic hepatitis B virus (HBV) infection. HBeAg and ALT level were determined in 636 asymptomatic hepatitis B surface antigen carriers. There was no significant ...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Tsai JF,Chuang LY,Jeng JE,Ho MS,Lin ZY,Hsieh MY,Wang LY,Tsai JH

    更新日期:2000-01-01 00:00:00

  • Nitric oxide: a regulator of mucosal defense and injury.

    abstract::There is an abundance of evidence that nitric oxide plays a critical role in regulating several components of gastrointestinal mucosal defense. Suppression of nitric oxide synthesis increases susceptibility to injury, while administration of nitric oxide donors increases resistance to injury. On the other hand, nitric...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章,评审


    authors: Elliott SN,Wallace JL

    更新日期:1998-12-01 00:00:00

  • Cellular membrane fluidity measurement by fluorescence polarization in indomethacin-induced gastric cellular injury in vitro.

    abstract:BACKGROUND:Gastric complications of indomethacin involve generation of reactive oxygen species, which induce gastric mucosal injury via lipid peroxidation of cell membranes. Peroxidation by reactive oxygen species alters the amounts of unsaturated fatty acids in the cell membrane and thus affects membrane fluidity. Ind...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Kaneko T,Matsui H,Shimokawa O,Nakahara A,Hyodo I

    更新日期:2007-12-01 00:00:00

  • Primary intestinal lymphangiectasia successfully treated with octreotide.

    abstract::A 21-year-old man with diarrhea and edema was admitted to our hospital and diagnosed with protein-losing enteropathy caused by primary intestinal lymphangiectasia. He was placed, in turn, on a low-fat diet, an elemental diet, and, subsequently, fasting therapy with total parenteral nutrition (TPN) support. However, hi...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Kuroiwa G,Takayama T,Sato Y,Takahashi Y,Fujita T,Nobuoka A,Kukitsu T,Kato J,Sakamaki S,Niitsu Y

    更新日期:2001-02-01 00:00:00

  • Sex-related influence of angiotensin-converting enzyme polymorphisms on fibrosis progression due to recurrent hepatitis C after liver transplantation.

    abstract:BACKGROUND:Experimental evidence and clinical studies suggest that the renin-angiotensin system and its inhibitors may play a role in regulating the mechanisms of liver fibrosis development. The present study aimed to verify whether carriage of specific angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) all...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Fabris C,Toniutto P,Bitetto D,Minisini R,Fornasiere E,Smirne C,Pirisi M

    更新日期:2007-07-01 00:00:00

  • Early activation of interferon-stimulated genes in human liver allografts: relationship with acute rejection and histological outcome.

    abstract:BACKGROUND:Innate immunity mechanisms have been shown to play a paramount role in organ transplantation. Our aim was to investigate the hypothesis that activation of the interferon system may affect clinically relevant outcomes, such as acute rejection and/or early fibrosis progression, after liver transplantation. ME...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Minisini R,Giarda P,Grossi G,Bitetto D,Toniutto P,Falleti E,Avellini C,Occhino G,Fabris C,Pirisi M

    更新日期:2011-11-01 00:00:00

  • Esophagectomy for superficial esophageal cancer after non-curative endoscopic resection.

    abstract:BACKGROUND:Additional surgical treatment after non-curative endoscopic resection for superficial esophageal cancer should be considered unless the tumor is pathologically proven to be categorized within the absolute indication of endoscopic resection. However, the significance of this treatment strategy has been poorly...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Saeki H,Watanabe M,Mine S,Shigaki H,Oya S,Ishiyama A,Tsuchida T,Fujisaki J,Baba H,Maehara Y,Sano T

    更新日期:2015-04-01 00:00:00

  • An expert review on the use of tenofovir alafenamide for the treatment of chronic hepatitis B virus infection in Asia.

    abstract::Asia has intermediate-to-high prevalence and high morbidity of hepatitis B virus (HBV) infection. The use of guideline-recommended nucleos(t)ide analogs with high barrier to resistance, such as entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF), is one of the key interventions for cu...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章,评审


    authors: Charlton MR,Alam A,Shukla A,Dashtseren B,Lesmana CRA,Duger D,Payawal DA,Duy Cuong D,Jargalsaikhan G,Cua IHY,Sollano JD,Singh KR,Madan K,Win KM,Kyi KP,Tun KS,Salih M,Rastogi M,Saraf N,Thuy PTT,Hien PTD,Gani RA,

    更新日期:2020-09-01 00:00:00

  • The efficacy of nocturnal administration of branched-chain amino acid granules to improve quality of life in patients with cirrhosis.

    abstract:BACKGROUND:Nocturnal administration of branched-chain amino acid (BCAA) granules improves serum albumin levels in patients with cirrhosis. However, it is unclear whether or not this administration method can improve the patients' quality of life (QOL). In this study, we aimed to investigate the efficacy of BCAA granule...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Hidaka H,Nakazawa T,Kutsukake S,Yamazaki Y,Aoki I,Nakano S,Asaba N,Minamino T,Takada J,Tanaka Y,Okuwaki Y,Watanabe M,Shibuya A,Koizumi W

    更新日期:2013-02-01 00:00:00

  • Clinical utility of quantitative HBsAg in natural history and nucleos(t)ide analogue treatment of chronic hepatitis B: new trick of old dog.

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    authors: Tseng TC,Kao JH

    更新日期:2013-01-01 00:00:00

  • The protective effect of catechin on gastric mucosal lesions in rats, and its hormonal mechanisms.

    abstract:BACKGROUND:Catechin, a polyphenol contained in tea (a cup of tea contains approximately 0.1% [w/v] catechin), has various physiological effects. The aim of this study was to investigate the mechanism of the inhibitory effect of catechin on gastric mucosal lesions. METHODS:We studied the effect of catechin on gastric m...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Sato H,Matsui T,Arakawa Y

    更新日期:2002-01-01 00:00:00

  • A case of gallbladder cancer associated with a common bile duct neuroma, and a cystic lesion of the liver with histologic findings similar to those of an inflammatory pseudotumor.

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    pub_type: 杂志文章


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  • Distribution of ghrelin-immunoreactive cells in human gastric mucosa: comparison with that of parietal cells.

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    更新日期:2005-04-01 00:00:00

  • PBC-AIH overlap syndrome with concomitant ITP and Hashimoto's disease with positivity for anti-centromere antibody.

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    更新日期:2014-10-01 00:00:00

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    pub_type: 杂志文章


    authors: Gribovskaja-Rupp I,Kwak JM,Takahashi T,Ludwig K

    更新日期:2014-05-01 00:00:00