Multiple mechanisms in indomethacin-induced impairment of hepatic cytochrome P450 enzymes in rats.

Abstract:

BACKGROUND & AIMS:Indomethacin impairs liver microsomal monooxygenase activities mediated by cytochrome P450 (CYP). We investigated the inhibition mechanism and the isoform selectivity in vitro and in vivo. METHODS:In an in vitro study, liver microsomes from male Wistar rats were preincubated with indomethacin and a reduced nicotinamide adenine dinucleotide phosphate-generating system, followed by assay of monooxygenase activities indicative of several CYP isoforms. In an in vivo study, rats were intraperitoneally treated with indomethacin, followed by preparation of microsomes and the enzyme assays. RESULTS:The preincubation of microsomes with indomethacin and reduced nicotinamide adenine dinucleotide phosphate decreased CYP3A2 activity but not any other isoforms. Kinetic analysis showed the mechanism-based inactivation of CYP3A2. The metabolism of [14C]indomethacin resulted in covalent binding to microsomal protein, which was diminished by inhibiting CYP3A enzyme. Administration of indomethacin caused impairment of not only CYP3A2 but also other CYP isoforms. Rats were protected from the impairment of the CYP enzymes except CYP3A2 by depleting macrophages and inhibiting inducible nitric oxide synthase. CONCLUSIONS:Metabolism of indomethacin causes inactivation of CYP3A2, which is the result of the covalent binding of its metabolite, whereas partially selective in vivo impairment of CYP isoforms is suggested to be indirect inhibition by inflammatory mediators probably released from Kupffer cells.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

Masubuchi Y,Masuda E,Horie T

doi

10.1053/gast.2002.31886

keywords:

subject

Has Abstract

pub_date

2002-03-01 00:00:00

pages

774-83

issue

3

eissn

0016-5085

issn

1528-0012

pii

S0016508502956428

journal_volume

122

pub_type

杂志文章
  • Proctitis after fecal diversion in Crohn's disease and its elimination with reanastomosis: implications for surgical management. Report of four cases.

    abstract::Diverting the fecal stream has been considered to affect the course of Crohn's disease favorably. Adverse effects on the distal segment have not previously been distinguished from clinical signs and symptoms. The course of four patients with Crohn's disease who underwent fecal diversion with an in situ rectum were obs...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:

    authors: Korelitz BI,Cheskin LJ,Sohn N,Sommers SC

    更新日期:1984-09-01 00:00:00

  • Gallstone dissolution in vitro using methyl tert-butyl ether: radiologic selection criteria.

    abstract::Methyl tert-butyl ether dissolves cholesterol gallbladder stones when infused through a percutaneous transhepatic catheter. All gallstones, however, contain noncholesterol components that are insoluble in lipid solvents and may be too large to be aspirated through a small catheter or flushed from the gallbladder. To i...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/s0016-5085(12)90345-5

    authors: Nelson PE,Moyer TP,Thistle JL

    更新日期:1990-05-01 00:00:00

  • Overt hepatic encephalopathy precipitated by zinc deficiency.

    abstract::Encephalopathy in liver disease may be unresponsive to protein restriction, lactulose, and neomycin. Zinc supplements have been reported to improve psychometric performance in liver cirrhosis, but the importance of zinc deficiency in overt hepatic encephalopathy has not yet been clearly established. A patient with sev...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/0016-5085(91)90290-2

    authors: Van der Rijt CC,Schalm SW,Schat H,Foeken K,De Jong G

    更新日期:1991-04-01 00:00:00

  • Induction and down-regulation of Sox17 and its possible roles during the course of gastrointestinal tumorigenesis.

    abstract:BACKGROUND & AIMS:The activation of Wnt/beta-catenin signaling causes the development of gastric and colon cancers. Sox17 represses Wnt/beta-catenin signaling and is down-regulated in colon cancer. This study was designed to elucidate the role of Sox17 during the course of gastrointestinal tumorigenesis. METHODS:Sox17...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2009.06.041

    authors: Du YC,Oshima H,Oguma K,Kitamura T,Itadani H,Fujimura T,Piao YS,Yoshimoto T,Minamoto T,Kotani H,Taketo MM,Oshima M

    更新日期:2009-10-01 00:00:00

  • Distribution of aneuploid cell populations in ulcerative colitis with dysplasia or cancer.

    abstract::Flow cytometry was used to detect the presence and assess the distribution of aneuploid cell populations in eight proctocolectomy specimens from patients with ulcerative colitis. Mucosal samples were taken according to a systematic protocol for flow cytometry, the surrounding tissue was examined histologically, and th...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/0016-5085(91)90068-v

    authors: Levine DS,Rabinovitch PS,Haggitt RC,Blount PL,Dean PJ,Rubin CE,Reid BJ

    更新日期:1991-11-01 00:00:00

  • Acknowledging joint first authors of published work: the time has come.

    abstract::We are delighted to introduce a new and simple format in the references section of the articles we publish in Gastroenterology that highlights joint first authors of citations. We believe this is an important step to acknowledging equal contribution to published work as research becomes increasingly team-oriented and ...

    journal_title:Gastroenterology

    pub_type: 社论

    doi:10.1053/j.gastro.2012.08.009

    authors: Dubnansky E,Omary MB

    更新日期:2012-10-01 00:00:00

  • Expression of 5-HT3 receptors in the rat gastrointestinal tract.

    abstract:BACKGROUND & AIMS:Functional effects mediated via the 5-hydroxytryptamine3 receptor (5-HT3R) can be elicited from both extrinsic and intrinsic neurons innervating the gastrointestinal (GI) tract. Clinically, 5-HT3 antagonists are important in the treatment of emesis and have been used for the treatment of symptoms in f...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/gast.2002.34245

    authors: Glatzle J,Sternini C,Robin C,Zittel TT,Wong H,Reeve JR Jr,Raybould HE

    更新日期:2002-07-01 00:00:00

  • Stimulation of jejunal mucosal protein synthesis by luminal glucose. Effects with luminal and vascular leucine in fed and fasted rats.

    abstract::This study was conducted to determine whether short-term (1.75 h) luminal glucose perfusion increases the mucosal protein synthesis rate in rat small intestine. A luminal perfusate containing 56 mM glucose was compared with a control perfusate containing mannitol in two jejunal segments constructed in the same animal....

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:

    authors: Weber FL Jr,Fresard KM,Veach GL

    更新日期:1989-03-01 00:00:00

  • Hepatic sinusoidal endothelial cell G1/S arrest correlates with severity of alcoholic liver injury in the rat.

    abstract:BACKGROUND/AIMS:Capillarization of the hepatic sinusoid occurs in alcoholic liver disease. Because endothelial cell proliferation is relevant to capillarization, we used the intragastric feeding rat model to evaluate the relationship between pathological liver injury and endothelial cell proliferation. METHODS:Male Wi...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/0016-5085(94)90132-5

    authors: Nanji AA,Tahan SR,Wei Y,Sadrzadeh SM

    更新日期:1994-09-01 00:00:00

  • Heterogeneities in ICC Ca2+ activity within canine large intestine.

    abstract:BACKGROUND & AIMS:In human and canine colon, both slow (slow waves, 2-8/min) and fast (myenteric potential oscillations [MPOs]; 16-20/min) electrical rhythms in the smooth muscle originate at the submucosal and myenteric borders, respectively. We used Ca(2+) imaging to investigate whether interstitial cells of Cajal (I...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2009.02.060

    authors: Lee HT,Hennig GW,Park KJ,Bayguinov PO,Ward SM,Sanders KM,Smith TK

    更新日期:2009-06-01 00:00:00

  • p53 protein accumulation in Barrett's metaplasia, dysplasia, and carcinoma: a follow-up study.

    abstract:BACKGROUND:There is a significant interobserver and intraobserver variation in grading dysplasia in Barrett's metaplasia. New markers are needed to optimize the assessment of potential risk of cancer development in these patients. The aim of this study is to explore the use of p53 as a marker of neoplastic progression ...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/0016-5085(93)91058-p

    authors: Younes M,Lebovitz RM,Lechago LV,Lechago J

    更新日期:1993-12-01 00:00:00

  • Fibroblast Growth Factor Signaling Controls Liver Size in Mice With Humanized Livers.

    abstract:BACKGROUND & AIMS:The ratio of liver size to body weight (hepatostat) is tightly controlled, but little is known about how the physiologic functions of the liver help determine its size. Livers of mice repopulated with human hepatocytes (humanized livers) grow to larger than normal; the human hepatocytes do not recogni...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2015.05.043

    authors: Naugler WE,Tarlow BD,Fedorov LM,Taylor M,Pelz C,Li B,Darnell J,Grompe M

    更新日期:2015-09-01 00:00:00

  • Saccharomyces boulardii inhibits secretagogue-mediated adenosine 3',5'-cyclic monophosphate induction in intestinal cells.

    abstract:BACKGROUND/AIMS:The yeast Saccharomyces boulardii inhibits the secretion induced by cholera toxin (CT) in rat jejunum. The present study was aimed at unraveling the mechanism by which S. boulardii protects intestinal cells against CT. METHODS:CT-induced adenosine 3',5'-cyclic monophosphate (cAMP) levels were measured ...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/s0016-5085(94)94403-2

    authors: Czerucka D,Roux I,Rampal P

    更新日期:1994-01-01 00:00:00

  • Na+/H+ exchange in isolated hamster enterocytes. Its major role in intracellular pH regulation.

    abstract::The intracellular pH (pHi) of isolated hamster intestinal cells was determined with three techniques: the null-point method with digitonin, the distribution of the weak acid 5,5-dimethyloxazolidine-2,4-dione, and the trapped fluorescent indicator 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. In physiologic saline, ...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/0016-5085(89)91492-3

    authors: Goré J,Hoinard C

    更新日期:1989-10-01 00:00:00

  • Smad7 controls resistance of colitogenic T cells to regulatory T cell-mediated suppression.

    abstract:BACKGROUND & AIMS:Foxp3-expressing regulatory T cells (Tregs) play a key role in the maintenance of the gut immune homeostasis, and an intact transforming growth factor (TGF)-beta signaling is required for their function. In inflammatory bowel disease (IBD), the TGF-beta signaling is impaired because of high expression...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2008.12.053

    authors: Fantini MC,Rizzo A,Fina D,Caruso R,Sarra M,Stolfi C,Becker C,Macdonald TT,Pallone F,Neurath MF,Monteleone G

    更新日期:2009-04-01 00:00:00

  • Chromosomal alterations in ulcerative colitis-related neoplastic progression.

    abstract:BACKGROUND & AIMS:It is unclear whether genomic derangement precedes the histological development of dysplasia in ulcerative colitis (UC)-related neoplastic progression. The primary aim of this study was to determine if chromosomal alterations occur early in the progression pathway of UC-related neoplasia. METHODS:Flu...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/s0016-5085(97)70173-2

    authors: Willenbucher RF,Zelman SJ,Ferrell LD,Moore DH 2nd,Waldman FM

    更新日期:1997-09-01 00:00:00

  • Pin1 interacts with a specific serine-proline motif of hepatitis B virus X-protein to enhance hepatocarcinogenesis.

    abstract:BACKGROUND AND AIMS:The peptidyl prolyl isomerase Pin1 frequently is overexpressed in hepatocellular carcinoma (HCC). Hepatitis B virus (HBV) is the most common etiologic agent in HCC, and its encoded X-protein (HBx) is oncogenic and possesses a serine-proline motif that may bind Pin1. The role of Pin1 in hepatocarcino...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2006.12.030

    authors: Pang R,Lee TK,Poon RT,Fan ST,Wong KB,Kwong YL,Tse E

    更新日期:2007-03-01 00:00:00

  • Cigarette smoke aggravates experimental colitis in rats.

    abstract:BACKGROUND & AIMS:Tobacco smoking has a complex effect on intestinal inflammation, being protective in ulcerative colitis, whereas it aggravates Crohn's disease. The beneficial effect of smoking has been attributed to nicotine, but the mechanisms underlying the adverse effect are still under investigation. The aim of t...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/s0016-5085(99)70346-x

    authors: Galeazzi F,Blennerhassett PA,Qiu B,O'Byrne PM,Collins SM

    更新日期:1999-10-01 00:00:00

  • Ingestion of corrosive acids. Spectrum of injury to upper gastrointestinal tract and natural history.

    abstract::We have prospectively evaluated 41 patients who ingested acid for location, extent, severity, and outcome of the injury to the upper gastrointestinal tract. The injury was assessed within 36 h of acid intake by endoscopy or surgery, or at autopsy. Symptoms and signs were unreliable in predicting the extent and severit...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:

    authors: Zargar SA,Kochhar R,Nagi B,Mehta S,Mehta SK

    更新日期:1989-09-01 00:00:00

  • Genetic testing for inherited colon cancer.

    abstract::The genes associated with each of the inherited syndromes of colon cancer have now been identified, and genetic testing is available for diagnosis. These syndromes include familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, Peutz-Jeghers syndrome, juvenile polyposis syndrome, and, possibly, Cowd...

    journal_title:Gastroenterology

    pub_type: 杂志文章,评审

    doi:10.1053/j.gastro.2005.03.036

    authors: Burt R,Neklason DW

    更新日期:2005-05-01 00:00:00

  • The SH3 binding motif of HCV [corrected] NS5A protein interacts with Bin1 and is important for apoptosis and infectivity.

    abstract:BACKGROUND & AIMS:HCV nonstructural protein 5A (NS5A) has been implicated in regulating cell growth and interferon response. The NS5A protein contains proline-rich regions that are highly conserved among HCV genotypes and match Src homology 3 (SH3)-binding motifs (PxxP) found in various cellular signaling molecules. M...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2005.12.030

    authors: Nanda SK,Herion D,Liang TJ

    更新日期:2006-03-01 00:00:00

  • Long-term outcome of Helicobacter pylori-negative idiopathic bleeding ulcers: a prospective cohort study.

    abstract:BACKGROUND & AIMS:Helicobacter pylori-negative idiopathic ulcers are increasingly recognized. The secular trend and long-term outcome of this condition are unknown. METHODS:We prospectively studied consecutive patients with bleeding gastroduodenal ulcers from January to December 2000. The incidence and etiology of ulc...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2005.03.026

    authors: Hung LC,Ching JY,Sung JJ,To KF,Hui AJ,Wong VW,Leong RW,Chan HL,Wu JC,Leung WK,Lee YT,Chung SC,Chan FK

    更新日期:2005-06-01 00:00:00

  • Regulation of ICAM-1-mediated fibroblast-T cell reciprocal interaction: implications for modulation of gut inflammation.

    abstract:BACKGROUND & AIMS:Immune-nonimmune cell interactions modulate mucosal immunity. We investigated the expression of adhesion molecules by intestinal fibroblasts, the effect of immune cell-derived factor on fibroblast binding of T cells, and the consequences of interfering with adhesion molecule expression on fibroblast-T...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/s0016-5085(99)70447-6

    authors: Musso A,Condon TP,West GA,De La Motte C,Strong SA,Levine AD,Bennett CF,Fiocchi C

    更新日期:1999-09-01 00:00:00

  • Direct transhepatic measurement of portal vein pressure using a thin needle. Comparison with wedged hepatic vein pressure.

    abstract::A technique for the direct measurement of portal vein pressure in fully conscious patients is described. This uses a percutaneous transhepatic approach with a thin Chiba needle and is shown to be simple and safe. The technique has been applied to 123 patients with a variety of liver disorders and the pressure measurem...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:

    authors: Boyer TD,Triger DR,Horisawa M,Redeker AG,Reynolds TB

    更新日期:1977-04-01 00:00:00

  • Systemic lupus erythematosus and intestinal venulitis.

    abstract::A 22-yr-old woman with a 7-yr history of systemic lupus erythematosus presented with anasarca and a serum albumin of 0.8 g/dl. Renal and hepatic function were near normal; the major route of protein loss appeared to be the intestine. A full-thickness section of jejunum obtained at laparotomy demonstrated a severe, dif...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:

    authors: Weiser MM,Andres GA,Brentjens JR,Evans JT,Reichlin M

    更新日期:1981-09-01 00:00:00

  • Use of macroaggregated albumin lung perfusion scan to diagnose hepatopulmonary syndrome: a new approach.

    abstract:BACKGROUND & AIMS:We have reported that contrast echocardiography is a sensitive screening test for the hepatopulmonary syndrome (HPS). However, contrast echocardiography lacks specificity because many cirrhotic patients have positive study results with normal arterial blood gases and therefore do not fulfill criteria ...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/s0016-5085(98)70481-0

    authors: Abrams GA,Nanda NC,Dubovsky EV,Krowka MJ,Fallon MB

    更新日期:1998-02-01 00:00:00

  • Proinflammatory role of leukocyte-derived Egr-1 in the development of murine postoperative ileus.

    abstract:BACKGROUND & AIMS:Early growth response gene-1 (Egr-1) is an important inflammatory transcription factor. We hypothesize that leukocyte-derived Egr-1 plays a key inflammatory role in causing postoperative ileus. METHODS:Wild-type, Egr-1 knockout, and chimera mice (constructed by irradiation followed by injection with ...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2008.05.079

    authors: Schmidt J,Stoffels B,Moore BA,Chanthaphavong RS,Mazie AR,Buchholz BM,Bauer AJ

    更新日期:2008-09-01 00:00:00

  • Aging is associated with decreased pancreatic acinar cell regeneration and phosphatidylinositol 3-kinase/Akt activation.

    abstract:BACKGROUND & AIMS:The effects of aging on pancreatic acinar cell proliferation have not been clearly defined. Phosphatidylinositol 3-kinase (PI3K)-mediated phosphorylation of Akt is a critical step for proliferation of various cell types and insulin secretion from pancreatic endocrine cells; however, its role in acinar...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2005.03.016

    authors: Watanabe H,Saito H,Rychahou PG,Uchida T,Evers BM

    更新日期:2005-05-01 00:00:00

  • Bone disease in cholestatic liver disease.

    abstract::Osteopenia in the form of osteoporosis is a common clinical problem associated with chronic cholestatic liver disease, and clinical morbidity from atraumatic fractures is increasing as more patients with PBC and PSC undergo successful liver transplantation. In the absence of symptomatic fractures, the clinical diagnos...

    journal_title:Gastroenterology

    pub_type: 杂志文章,评审

    doi:10.1016/0016-5085(95)90033-0

    authors: Hay JE

    更新日期:1995-01-01 00:00:00

  • Expression of sterol 12alpha-hydroxylase alters bile acid pool composition in primary rat hepatocytes and in vivo.

    abstract:BACKGROUND & AIMS:The rate of 12alpha-hydroxylation of bile acid intermediates is believed to determine the ratio of cholic acid (CA) to chenodeoxycholic acid (CDCA) biosynthesis and the overall hydrophobicity of the bile acid pool. The aim of this study was to determine the effects of the level of expression of sterol...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/gast.2001.24833

    authors: Pandak WM,Bohdan P,Franklund C,Mallonee DH,Eggertsen G,Björkhem I,Gil G,Vlahcevic ZR,Hylemon PB

    更新日期:2001-06-01 00:00:00