Similarities between ileal Crohn’s disease and indomethacin experimental jejunal ulcers in the rat

Anthony, A; Pounder, RE; Dhillon, A. P.; Wakefield, AJ

doi:10.1046/j.1365-2036.2000.00694.x

Cited by 38 publications

(34 citation statements)

References 14 publications

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“…After the first week, these parameters returned to normal values. Moreover, a high increase of blood leukocyte levels was also observed, from 10,872 Ϯ 140 to 25,695 Ϯ 707 cells/mm 3 , followed by a cyclic oscillation of this parameter (Fig. 1A).…”

Section: Animal Monitoringmentioning

confidence: 92%

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Intestinal motor disorders associated with cyclical bacterial overgrowth in a rat model of enteritis

Porras¹,

Martín²,

Soler³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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Porras, Monica, María Teresa Martín, Mercè Soler, and Patri Vergara. Intestinal motor disorders associated with cyclical bacterial overgrowth in a rat model of enteritis. Am J Physiol Gastrointest Liver Physiol 287: G58 -G64, 2004. First published February 12, 2004 10.1152/ajpgi.00513.2003.-The aims of this study were: 1) to obtain an experimental model reproducing the characteristics of chronicity and spontaneous relapses found in inflammatory bowel disease (IBD) and 2) to correlate these changes with intestinal motility and bacteria translocation. For this purpose, two groups of Sprague-Dawley rats were used: a treated group that received two subcutaneous injections of indomethacin (7.5 mg/kg) 48 h apart and a control group that received saline. Blood leukocytes, TNF, and fecal parameters were monitored for 90 days after treatment. In treated rats, a cyclic oscillation of blood leukocytes and TNF concomitant with an inverse correlation of fecal output was observed. Treated rats were then selected either during their highest or lowest blood leukocyte values for motor activity and microbiological evaluation. Controls were obtained in age-matched rats. Rats with high leukocyte levels showed a decrease of motor activity. In contrast, animals with low leukocyte levels presented hypermotility. Bacterial overgrowth accompanied by bacterial translocation was found in the group with high leukocytes, whereas no differences were observed between the control and indomethacin groups during the lowest leukocyte phase. We obtained a model of IBD characterized by a chronic cyclic oscillation of intestinal motility, flora, and inflammatory blood parameters. During the high-leukocyte stage, motor activity decrease is related to bacterial translocation. This phase is followed by a reactive one characterized by hypermotility associated with a decrease in both bacterial growth and leukocytes. However, as in IBD, this reaction seems unable to prevent a return to relapse. inflammatory bowel disease; gastrointestinal motility; gut flora; leukocytes INFLAMMATORY BOWEL DISEASE (IBD) in its more common forms, Crohn's disease (CD) and ulcerative colitis, is characterized by presenting alternative phases of activity and quiescence and by its chronicity (11). Several studies (12,22,29) indicate an abnormal immune reactivity to intestinal flora as the cause for the inflammation, probably caused by impairment of the mucosal barrier function.Systemic administration of indomethacin in the rat has been used to cause inflammation of the small intestine, which presents some histopathological similarities to lesions found in CD (5, 37). It has been suggested that inhibition of cyclooxygenase activity induced by this drug alters mucosal permeability (7), facilitating the entry of bacteria and other harmful substances into the lamina propia and producing inflammation (24). Luminal bacteria seems to be critical to the induction of intestinal damage, because both germ-free rats (24) and animals treated with antibiotics (8) develop minimal lesions a...

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Section: Animal Monitoringmentioning

confidence: 92%

“…Histological similarities between the rat indomethacin model and CD are well known (3,5). However, because the described protocols using indomethacin cause extensive intestinal damage (19,37), studies could only be performed a few (27), we obtained rats with less-severe lesions, which allowed us to perform chronic studies.…”

Section: Discussionmentioning

confidence: 99%

Intestinal motor disorders associated with cyclical bacterial overgrowth in a rat model of enteritis

Porras¹,

Martín²,

Soler³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…An indirect proof of the role exerted by gut bacteria in the pathogenesis of NSAID enteropathy is represented by the similarities between indomethacin-induced intestinal damage and Crohn's disease [234,246]. Not only are these lesions anatomically (both macro-and microscopically) similar [246], but also sensitive to the same drugs, e.g.…”

Section: Prevention Of Nonsteroidal Anti-inflammatory Drug-induced Enmentioning

confidence: 99%

“…Not only are these lesions anatomically (both macro-and microscopically) similar [246], but also sensitive to the same drugs, e.g. sulfasalazine [234,247], steroids [234,247], immunosuppressive compounds [248], and antibiotics [234][235][236][237].…”

Section: Prevention Of Nonsteroidal Anti-inflammatory Drug-induced Enmentioning

confidence: 99%

Rifaximin, a Poorly Absorbed Antibiotic: Pharmacology and Clinical Potential

2005

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Rifaximin (4-deoxy-4′-methylpyrido[1′,2′-1,2]imidazo- [5,4-c]-rifamycin SV) is a synthetic antibiotic designed to modify the parent compound, rifamycin, in order to achieve low gastrointestinal (GI) absorption while retaining good antibacterial activity. Both experimental and clinical pharmacology clearly show that this compound is a nonsystemic antibiotic with a broad spectrum of antibacterial action covering Gram-positive and Gram-negative organisms, both aerobes and anaerobes. Being virtually nonabsorbed, its bioavailability within the GI tract is rather high with intraluminal and fecal drug concentrations that largely exceed the minimal inhibitory concentration values observed in vitro against a wide range of pathogenic organisms. The GI tract represents, therefore, the primary therapeutic target and GI infections the main indication. The appreciation of the pathogenic role of gut bacteria in several organic and functional GI diseases has increasingly broadened its clinical use, which is now extended to hepatic encephalopathy, small intestine bacterial overgrowth, inflammatory bowel disease and colonic diverticular disease. Potential indications include the irritable bowel syndrome and chronic constipation, Clostridium difficile infection and bowel preparation before colorectal surgery. Because of its antibacterial activity against the microorganism and the lack of strains with primary resistance, some preliminary studies have explored the rifaximin potential for Helicobacter pylori eradication. Oral administration of this drug, by getting rid of enteric bacteria, could also be employed to achieve selective bowel decontamination in acute pancreatitis, liver cirrhosis (thus preventing spontaneous bacterial peritonitis) and nonsteroidal anti-inflammatory drug (NSAID) use (lessening in that way NSAID enteropathy). This antibiotic has, therefore, little value outside the enteric area and this will minimize both antimicrobial resistance and systemic adverse events. Indeed, the drug proved to be safe in all patient populations, including young children. Although rifaximin has stood the test of time, it still attracts the attention of both basic scientists and clinicians. As a matter of fact, with the advancement of the knowledge on microbial-gut interactions in health and disease novel indications and new drug regimens are being explored. Besides widening the clinical use, the research on rifaximin is also focused on the synthesis of new derivatives and on the development of original formulations designed to expand the spectrum of its clinical use.

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“…[11][12][13][14] Similar observations have been made in animal models. 15,16) Recently, although selective COX-2 inhibitors have been developed that were expected to produce less gastric injury, they retain the ability to cause bowel damage. 8) These reports indicate that the methods for reducing the enteropathy are needed and important in NSAIDs therapy.…”

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confidence: 99%

An Herbal Medicine Orengedokuto Prevents Indomethacin-Induced Enteropathy

Miura

Fukutake

Yamamoto

et al. 2007

Biological & Pharmaceutical Bulletin

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Prostaglandin E2 (PGE2) is a key regulator of gastrointestinal, immunological, and mucosal homeostasis. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the prostaglandin-producing enzyme cyclooxygenases (COXs), and can induce serious complications, such as gastrointestinal damage, with long-term treatment. Orengedokuto (OGT), a Japanese traditional herbal medicine (Kampo medicine), is effective in various animal models of enteropathy. In the present study we examined whether OGT prevents enteropathy induced by NSAIDs in mice. Ulceration in the small intestine was induced with 2 subcutaneous injections of indomethacin (20 mg/kg body weight). Orally administered OGT prevented or reduced lethality, intestinal lesions, bleeding, increased serum nitrate/nitrite levels, and reduction of mucosal PGE2 induced by indomethacin. These beneficial effects of OGT were accompanied by increased production of PGE2 and interleukin 10 by isolated lamina propria mononuclear cells; COX-2 in these cells may be a major source of PGE2 in normal intestines. These findings suggest that OGT could be an effective therapeutic agent for the treatment of inflammatory bowel disease and adverse reactions to NSAIDs.Key words nonsteroidal anti-inflammatory drug; interleukin 10; herbal medicine; inflammatory bowel disease; prostaglandin E2

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Similarities between ileal Crohn’s disease and indomethacin experimental jejunal ulcers in the rat

Abstract: For anatomical reasons apparently related to the vasculature of the human and rodent small bowel, specific sites along the mesenteric margin are susceptible to Crohn's disease ulceration and NSAID damage, respectively.

Cited by 38 publications

References 14 publications

Intestinal motor disorders associated with cyclical bacterial overgrowth in a rat model of enteritis

Intestinal motor disorders associated with cyclical bacterial overgrowth in a rat model of enteritis

Rifaximin, a Poorly Absorbed Antibiotic: Pharmacology and Clinical Potential

An Herbal Medicine Orengedokuto Prevents Indomethacin-Induced Enteropathy

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