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


  • Effects of vedolizumab in Japanese patients with Crohn's disease: a prospective, multicenter, randomized, placebo-controlled Phase 3 trial with exploratory analyses.

    abstract:BACKGROUND:Vedolizumab is a gut-selective humanized antibody that binds the α4β7 integrin. We evaluated efficacy and safety of vedolizumab in Japanese patients with moderate-to-severe Crohn's disease (CD). METHODS:In this Phase 3, double-blind study (NCT02038920), 157 patients were randomized to receive intravenous ve...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Watanabe K,Motoya S,Ogata H,Kanai T,Matsui T,Suzuki Y,Shikamura M,Sugiura K,Oda K,Hori T,Araki T,Watanabe M,Hibi T

    更新日期:2020-03-01 00:00:00

  • Endoscopic and histopathological characteristics suggesting the presence of gastric mucosal high grade neoplasia foci in cases initially diagnosed as gastric mucosal low grade neoplasia by forceps biopsy in Korea.

    abstract:BACKGROUND:As biopsy sites may miss coexisting gastric mucosal high grade neoplasia (HGN) foci, making a diagnosis of gastric mucosal low grade neoplasia (LGN) based only on forceps biopsy specimens can be inaccurate. Therefore, to achieve an accurate diagnosis, endoscopic mucosal resection (EMR) of the entire lesion i...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Min BH,Kim KM,Kim ER,Park CK,Kim JJ,Lee H,Lee JH,Chang DK,Kim YH,Rhee PL,Rhee JC

    更新日期:2011-01-01 00:00:00

  • Expression of vacuolating cytotoxin in clinical isolates of Helicobacter pylori.

    abstract::Our objective was to determine whether the prevalence of vacuolating cytotoxin production differed among Helicobacter pylori isolates obtained from patients with chronic gastritis, gastric ulcer, or duodenal ulcer. We examined the vacuolating cytotoxin production of 114 clinical H. pylori isolates in rabbit gastic epi...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Kodama K,Fujioka T,Ito A,Kubota T,Murakami K,Nasu M

    更新日期:1996-11-01 00:00:00

  • Analysis of 6381 hepatocellular carcinoma patients in southern Taiwan: prognostic features, treatment outcome, and survival.

    abstract:BACKGROUND:This hospital-based analysis was conducted to identify prognostic factors of hepatocellular carcinoma (HCC) in a hepatitis B virus endemic area. METHODS:A total of 6381 HCC cases, diagnosed from 1986 to 2002, were enrolled, and 2890 (42.3%) of them were not treated. Survival rates were analyzed by correlati...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Changchien CS,Chen CL,Yen YH,Wang JH,Hu TH,Lee CM,Wang CC,Cheng YF,Huang YJ,Lin CY,Lu SN

    更新日期:2008-01-01 00:00:00

  • Vascular endothelial growth factor receptor 1 signaling facilitates gastric ulcer healing and angiogenesis through the upregulation of epidermal growth factor expression on VEGFR1+CXCR4 + cells recruited from bone marrow.

    abstract:BACKGROUND:Angiogenesis is essential for gastric ulcer healing. Recent results suggest that vascular endothelial growth factor receptor 1 (VEGFR1), which binds to VEGF, promotes angiogenesis. In the present study, we investigated the role of VEGFR1 signaling in gastric ulcer healing and angiogenesis. METHODS:Gastric u...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Sato T,Amano H,Ito Y,Eshima K,Minamino T,Ae T,Katada C,Ohno T,Hosono K,Suzuki T,Shibuya M,Koizumi W,Majima M

    更新日期:2014-03-01 00:00:00

  • Epidemiology and clinical characteristics of GERD in the Japanese population.

    abstract::We reviewed articles on the epidemiology and clinical characteristics of gastroesophageal reflux disease (GERD) in Japan to clarify these features of GERD in this country. Although the definition of GERD depends on the individual study, the prevalence of GERD has been increasing since the end of the 1990s. The reasons...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章,评审


    authors: Fujiwara Y,Arakawa T

    更新日期:2009-01-01 00:00:00

  • The genetic classification of pancreatic neoplasia.

    abstract::Cancer is caused by the accumulation of inherited and/or acquired alterations in specific genes. The recent decline in the cost of DNA sequencing has allowed tumor sequencing to be conducted on a large scale, which, in turn, has led to an unprecedented understanding of the genetic events that drive neoplasia. This und...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章,评审


    authors: Matthaei H,Semaan A,Hruban RH

    更新日期:2015-05-01 00:00:00

  • Incidence and clinical outcomes of intestinal Behçet's disease in Korea, 2011-2014: a nationwide population-based study.

    abstract:BACKGROUND:Intestinal Behçet's disease (BD) is very rare, and epidemiologic data regarding BD are scarce. Moreover, there have been no population-based studies focusing on intestinal BD. We conducted a nationwide population-based study to examine the incidence and clinical course of Korean patients with intestinal BD. ...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Han M,Jung YS,Kim WH,Cheon JH,Park S

    更新日期:2017-08-01 00:00:00

  • Immunoreactivity of antimitochondrial autoantibodies in Japanese patients with primary biliary cirrhosis.

    abstract::The incidence and prevalence of primary biliary cirrhosis show wide geographic differences. The frequency of this disease in Japan is lower than in Northern Europe. To elucidate the immunoreactivity of serum with enzymes of the 2-oxo-acid dehydrogenase complex (2-OADC) and the M2 mitochondrial antigenic complex in Jap...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Omagari K,Rowley MJ,Jois JA,Feeney SJ,Komatsu K,Maeda T,Onishi S,Yamazaki K,Suzuki K,Galperin C,Mackay IR

    更新日期:1996-02-01 00:00:00

  • A case of choledochal cyst associated with adenocarcinoma exhibiting sarcomatous features.

    abstract::One complication of choledochal cyst in adulthood is the development of secondary carcinoma, usually well-differentiated adenocarcinoma. We report a case of extrahepatic bile duct carcinoma associated with choledochal cyst and presenting predominantly sarcomatous features. The patient was a 52-year-old female who pres...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Nonomura A,Mizukami Y,Matsubara F,Ueda H

    更新日期:1994-10-01 00:00:00

  • Granular cell tumor occurring in the sigmoid colon treated by endoscopic mucosal resection using a transparent cap (EMR-C).

    abstract::A case of granular cell tumor occurring in the sigmoid colon is reported. The patient, a 56-year-old man, visited our hospital for further evaluation of occult blood in his stool. Endoscopic examination revealed a yellowish, hemispheric submucosal tumor (SMT) with redness, about 6 mm in diameter, in the sigmoid colon....

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章,评审


    authors: Endo S,Hirasaki S,Doi T,Endo H,Nishina T,Moriwaki T,Nakauchi M,Masumoto T,Tanimizu M,Hyodo I

    更新日期:2003-01-01 00:00:00

  • Surveillance programmes for neoplasia in colitis.

    abstract::Patients with longstanding extensive colitis, both ulcerative colitis and Crohn's colitis, have an increased risk of developing colorectal cancer. Because of this risk, colonoscopic surveillance for neoplasia is recommended by most authorities. Although there has been no randomised controlled trial to demonstrate surv...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Rutter MD

    更新日期:2011-01-01 00:00:00

  • A population-based case-control study: proton pump inhibition and risk of hip fracture by use of bisphosphonate.

    abstract:BACKGROUND:Studies on the risk of osteoporotic fractures related to the use of proton pump inhibitors (PPIs) have been inconsistent. One recent cohort study reported that there was an interaction between PPIs and bisphosphonates (BPs). Thus we performed a case-control study aimed at evaluating the risk of hip fractures...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Lee J,Youn K,Choi NK,Lee JH,Kang D,Song HJ,Park BJ

    更新日期:2013-09-01 00:00:00

  • Clinicopathological features of liver injury in patients with type 2 diabetes mellitus and comparative study of histologically proven nonalcoholic fatty liver diseases with or without type 2 diabetes mellitus.

    abstract:BACKGROUND:The Japan Society of Diabetes Mellitus reported that the leading cause of death in patients with diabetes mellitus (DM) was chronic liver disease; however, there are limited studies investigating the cause of liver injury in these patients. Our study aimed to clarify the clinicopathological features of liver...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章,多中心研究


    authors: Shima T,Uto H,Ueki K,Takamura T,Kohgo Y,Kawata S,Yasui K,Park H,Nakamura N,Nakatou T,Tanaka N,Umemura A,Mizuno M,Tanaka J,Okanoue T

    更新日期:2013-04-01 00:00:00

  • Real-time energy metabolism of intestine during arterial versus venous occlusion in the rat.

    abstract:BACKGROUND:Although it is less frequently encountered, mesenteric vein occlusion poses as important a problem as mesenteric artery occlusion. The energy metabolism of intestinal tissue during venous occlusion and reperfusion was studied. METHODS:Male Wistar rats were studied in four groups of 17 animals each. Intestin...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Kimura M,Kataoka M,Kuwabara Y,Sato A,Sugiura M,Fujii Y

    更新日期:2003-01-01 00:00:00

  • Hepatocellular carcinoma in patients with nonalcoholic steatohepatitis.

    abstract:BACKGROUND:There have been few reports on hepatocellular carcinoma (HCC) in nonalcoholic steatohepatitis (NASH) and the natural history of NASH. Accordingly, we assessed the clinical features of HCC in NASH, the risk factors for HCC, and natural history of NASH with advanced fibrosis. PATIENTS AND METHODS:There were 3...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Hashimoto E,Yatsuji S,Tobari M,Taniai M,Torii N,Tokushige K,Shiratori K

    更新日期:2009-01-01 00:00:00

  • Loss of diurnal variation in ornithine decarboxylase and apoptosis in small intestine of Mongolian gerbils.

    abstract::The aim of this study was to examine the diurnal variations in ornithine decarboxylase (ODC) activity and apoptosis in the small intestinal mucosa of Mongolian gerbils. First, the feeding, drinking, and ambulatory patterns of the gerbils were recorded. The results indicated that Mongolian gerbils lost diurnal cyclicit...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Kashiwagi Y,Fujimoto K,Iwakiri R,Yoshida T,Noda T,Aw TY,Niho Y,Sakata T

    更新日期:2000-01-01 00:00:00

  • Intrahepatic cholangiocarcinoma with increased serum CYFRA 21-1 level.

    abstract::CYFRA 21-1 is a fragment of cytokeratin 19 (CK 19). Four patients with large intrahepatic (or peripheral) cholangiocarcinoma (CC) and high serum levels of CYFRA 21-1 (normal, < or = 2 ng/ml) are reported. CYFRA 21-1 levels exceeded 9 ng/ml in all 4 patients. Carcinoembryonic antigen (CEA), was high in 1 (CEA; normal r...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Kashihara T,Ohki A,Kobayashi T,Sato T,Nishizawa H,Ogawa K,Tako H,Kawakami F,Tsuji M,Tamaoka K

    更新日期:1998-06-01 00:00:00

  • Epidemiological study of ulcerative colitis in Japan: incidence and familial occurrence. The Epidemiology Group of the Research Committee of Inflammatory Bowel Disease in Japan.

    abstract::Epidemiological studies of ulcerative colitis (UC) have been conducted once every year since 1973 in Japan. The number of participating hospitals in 1429 and they are distributed throughout Japan. A total number of 10819 patients diagnosed with UC have been registered, including 197 patients with a positive family his...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Kitahora T,Utsunomiya T,Yokota A

    更新日期:1995-11-01 00:00:00

  • Role of extravariceal collateral channels in the development of portal-hypertensive gastropathy before and after sclerotherapy.

    abstract::We investigated whether extravariceal collateral pattern contributed to the development of portal-hypertensive gastropathy (PHG) before and after sclerotherapy. Ninety-nine patients with cirrhosis and large esophageal varices were examined in this retrospective study. They were divided into four groups according to tr...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Nakayama M,Iwao T,Oho K,Toyonaga A,Tanikawa K

    更新日期:1998-04-01 00:00:00

  • Phospholipid turnover in the inflamed intestinal mucosa: arachidonic acid-rich phosphatidyl/plasmenyl-ethanolamine in the mucosa in inflammatory bowel disease.

    abstract::Cytosolic phospholipase A2 (PLase A2) is activated by low Ca2+ concentrations and translocates from the cytosol to the cell membrane, releasing arachidonic acid; the arachidonic acid cascade then leads to the production of many inflammatory mediators. The aim of this study, accordingly, was to investigate the role of ...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Morita H,Nakanishi K,Dohi T,Yasugi E,Oshima M

    更新日期:1999-02-01 00:00:00

  • Prognostic impact of primary tumor location in Stage III colorectal cancer-right-sided colon versus left-sided colon versus rectum: a nationwide multicenter retrospective study.

    abstract:BACKGROUND:Previous studies investigating the impact of tumor location on colorectal cancer prognosis only compared two groups by location, e.g., 'right-sided colon vs. left-sided colon,' 'colon vs. rectum,' and 'right-sided (right-sided colon) vs. left-sided (left-sided colon and rectum).' This nationwide multicenter ...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Shida D,Inoue M,Tanabe T,Moritani K,Tsukamoto S,Yamauchi S,Sugihara K,Kanemitsu Y

    更新日期:2020-10-01 00:00:00

  • Cardiac metastasis from squamous cell carcinoma of gallbladder.

    abstract::A 65-year-old woman was admitted to our hospital with the diagnosis of gallbladder tumor. Right extended hepatic lobectomy plus lymph node dissection of the hepatoduodenal ligament and left hepaticojejunostomy with Roux-en-Y reconstruction was performed in July, 1993. The gallbladder tumor was histologically proven to...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Suganuma M,Marugami Y,Sakurai Y,Ochiai M,Hasegawa S,Imazu H,Matsubara T,Funabiki T,Kuroda M

    更新日期:1997-12-01 00:00:00

  • Chromosome spreading techniques for primary gastrointestinal tumors.

    abstract::The requirement for well spread out chromosomes for the cytogenetic analysis of primary gastrointestinal tumors led us to develop new techniques. These techniques involved two main procedures: (1) preliminary incubation with culture medium in the presence of collagenase, Dispase, and colcemid, for 3 h, and (2) treatme...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Sasai K,Tanaka R,Kawamura M,Honjo K,Matsunaga N,Nakada T,Homma K,Fujimura H

    更新日期:1996-08-01 00:00:00

  • Pharmacologic prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis: protease inhibitors and NSAIDs in a meta-analysis.

    abstract::Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis is the most frequent complication of ERCP. Several meta-analyses have examined the effects of protease inhibitors (gabexate mesilate, ulinastatin, and nafamostat mesilate) and non-steroidal anti-inflammatory drugs (NSAIDs) on post-ERCP pancreatiti...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章,meta分析,评审


    authors: Yuhara H,Ogawa M,Kawaguchi Y,Igarashi M,Shimosegawa T,Mine T

    更新日期:2014-03-01 00:00:00

  • Recurrence of hepatocellular carcinoma 102 months after successful eradication and removal of membranous obstruction of the inferior vena cava.

    abstract::We report a 54-year-old Japanese woman who developed liver tumors 102 months after hepatic resection for hepatocellular carcinoma (HCC) and percutaneous transluminal angioplasty (PTA) for membranous obstruction of the inferior vena cava (MOVC), which is one form of Budd-Chiari syndrome. In the present admission workup...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Takamura M,Ichida T,Yokoyama J,Matsuda Y,Nomoto M,Aoyagi Y

    更新日期:2004-07-01 00:00:00

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

    abstract::We report a case of primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome with concurrent idiopathic thrombocytopenic purpura (ITP) and Hashimoto's disease with positivity for anticentromere antibody. The patient was a 64-year-old woman with symptoms of jaundice and general fatigue. About 30 year...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Arakawa Y,Amaki S,Miyakawa H,Sakai T,Gotou I,Tanaka N,Moriyama M,Iwasaki A,Sugitani M,Arakawa Y

    更新日期:2004-01-01 00:00:00

  • Oral nanotherapeutics: effect of redox nanoparticle on microflora in mice with dextran sodium sulfate-induced colitis.

    abstract:BACKGROUND:Patients with ulcerative colitis (UC) exhibit overproduction of reactive oxygen species (ROS) and imbalance of colonic microflora. We previously developed a novel redox nanoparticle (RNP(O)), which effectively scavenged ROS in the inflamed mucosa of mice with dextran sodium sulfate (DSS)-induced colitis afte...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Vong LB,Yoshitomi T,Morikawa K,Saito S,Matsui H,Nagasaki Y

    更新日期:2014-05-01 00:00:00

  • Eradication of Helicobacter pylori for primary gastric cancer and secondary gastric cancer after endoscopic mucosal resection.

    abstract::Because most gastric cancers develop from a background of Helicobacter pylori-infected gastric mucosa, H. pylori plays an important role in gastric carcinogenesis. Therefore, eradication of H. pylori may inhibit the incidence of gastric cancers. In experimental studies, H. pylori eradication has proved to act as a pro...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章,评审


    authors: Kato M,Asaka M,Ono S,Nakagawa M,Nakagawa S,Shimizu Y,Chuma M,Kawakami H,Komatsu Y,Hige S,Takeda H

    更新日期:2007-01-01 00:00:00

  • A new ABCB11 mutation in two Italian children with familial intrahepatic cholestasis.

    abstract::Progressive familial intrahepatic cholestasis (PFIC) syndromes are characterized by defects in transporters of conjugated bile acids into the bile canaliculus. Three genes (ATP8B1, ABCB11, ABCB4) are associated with the different forms, but no easy genotype-phenotype correlations help in the prioritization for gene te...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Nobili V,Di Giandomenico S,Francalanci P,Callea F,Marcellini M,Santorelli FM

    更新日期:2006-06-01 00:00:00