TITLE

EP4 agonist alleviates indomethacin-induced gastric lesions and promotes chronic gastric ulcer healing

AUTHOR(S)
Guang-Liang Jiang; Wha Bin Im; Donde, Yariv; Wheeler, Larry A.
PUB. DATE
November 2009
SOURCE
World Journal of Gastroenterology;11/7/2009, Vol. 15 Issue 41, p5149
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
AIM: To investigate EP4-selective agonist effect on indomethacin-induced gastric lesions and on the spontaneous healing of chronic gastric ulcers. METHODS: In a mouse model of gastric bleeding with high dose of indomethacin (20 mg/kg), an EP4-selective agonist was administered orally. Stomach lesions and gastric mucous regeneration were monitored. In a mouse model of chronic gastric ulcer induced by acetic acid, EP4 agonist effect on the healing of chronic gastric ulcer was evaluated in the presence or absence of low dose indomethacin (3 mg/kg). In cultured human gastric mucous cells, EP4 agonist effect on indomethacin-induced apoptosis was assessed by flow cytometry. RESULTS: The EP4-selective agonist reduced high dose indomethacin-induced acute hemorrhagic damage and promoted mucous epithelial regeneration. Low-dose indomethacin aggravated ulcer bleeding and inflammation, and delayed the healing of the established chronic gastric ulcer. The EP4 agonist, when applied locally, not only offset indomethacin-induced gastric bleeding and inflammation, but also accelerated ulcer healing. In the absence of indomethacin, the EP4 agonist even accelerated chronic gastric ulcer healing and suppressed inflammatory cell infiltration in the granulation tissue. In vitro, the EP4 agonist protected human gastric mucous cells from indomethacin-induced apoptosis. CONCLUSION: EP4-selective agonist may prevent indomethacin-induced gastric lesions and promote healing of existing and indomethacin-aggravated gastric ulcers, via promoting proliferation and survival of mucous epithelial cells.
ACCESSION #
45308180

 

Related Articles

  • Prostaglandins and Acid Peptic Disease. Sontag, Stephen J. // American Journal of Gastroenterology;Nov1986, Vol. 81 Issue 11, p1021 

    Naturally occurring PGs are considered important in maintaining the integrity of the gastrointestinal mucosa. Evidence indicates that synthetic analogs of PGs heal gastroduodenal ulcers in doses that suppress gastric acid. No consistent benefit of this class of drugs compared with already...

  • Mechanisms Behind the Increased Vulnerability of the Aging Stomach to NSAID-Related Injury: Perhaps Not As Simple As We May Think. Tang, Raymond; Chan, Francis // Digestive Diseases & Sciences;Jan2013, Vol. 58 Issue 1, p11 

    No abstract available.

  • Factors Influencing Effects of Specific COX-2 Inhibitor NSAIDs on Growth and Differentiation of Mouse Osteoblasts on Titanium Surfaces. Arpornmaeklong, Premijt; Akarawatcharangura, Butsakorn; Pripatnanont, Prisana // International Journal of Oral & Maxillofacial Implants;2008, Vol. 23 Issue 6, p1071 

    Purpose: To investigate the influence of exposure time and stages of cell growth on the effects of specific COX-2 inhibitor NSAIDs on growth and differentiation of osteoblasts on smooth titanium surfaces. Materials and Methods: The study was categorized into 5 groups: group A, 0.1 μM...

  • Effect of Ketoprofen and Indomethacin on Methotrexate Pharmacokinetics in Mice Plasma and Tumor Tissues. Elmorsi, Yasmine M.; El-Haggar, Sahar M.; Ibrahim, Osama M.; Mabrouk, Mokhtar M. // Journal of Applied Pharmaceutical Science;Jun2012, Vol. 2 Issue 6, p90 

    Methotrexate (MTX) has been used in combination with nonsteroidal antiinflammatory drugs (NSAIDs) in the treatment of inflammatory diseases and malignancies. Severe adverse effects with this combination may occur, usually resulting from inhibition of renal transporters. Solid Ehrlich Carcinoma...

  • β-GLUCAN-INDOMETHACIN COMBINATION PRODUCES NO LETHAL EFFECTS. Vetvicka, Vaclav; Vetvickova, Jana // Biomedical Papers of the Medical Faculty of Palacky University i;2009, Vol. 153 Issue 2, p111 

    Background: The most important quality of β-glucans and the reason why so much attention has been devoted to them are their physiological effects. They are typical biological response modifiers with pronounced immunomodulating activity. However, some questions about possible side effects...

  • Preventing Ulcers. Herthel, Doug; Abelshauser, Reina // Dressage Today;May2014, Vol. 20 Issue 9, p21 

    The article discusses symptoms and management of gastric ulcers in horses. It instructs looking for clinical signs of ulcers in horses including mild to severe non-specific colic, excessive salivation, and mild diarrhea. It mentions behavioral changes and problems caused by ulcer in horses, such...

  • Protective effect of mirtazapine on indomethacin-induced ulcer in rats and its relationship with oxidant and antioxidant parameters. Bilici, Mehmet; Ozturk, Cengiz; Dursun, Hakan; Albayrak, Fatih; Saglam, Mustafa Bahadir; Uyanik, Abdullah; Gulaboglu, Mine; Tekin, Salim Basol // Digestive Diseases & Sciences;Sep2009, Vol. 54 Issue 9, p1868 

    Even though there are many drugs for the treatment of gastric ulcers, these drugs sometimes cannot succeed. Since the 1950s, antidepressant drugs have been used for several non-psychiatric indications. A lot of antidepressant drugs have been shown experimentally to produce antiulcer activity in...

  • The inflammatory network in the gastrointestinal tumor microenvironment: lessons from mouse models. Oshima, Hiroko; Oshima, Masanobu // Journal of Gastroenterology;Feb2012, Vol. 47 Issue 2, p97 

    Accumulating evidence has indicated that inflammatory responses are important for cancer development. Epidemiological studies have shown that regular use of non-steroidal anti-inflammatory drugs (NSAIDs) reduces the risk of colon cancer development. Subsequently, mouse genetic studies have shown...

  • Molecular Mechanisms Elucidating Why Old Stomach Is More Vulnerable to Indomethacin-Induced Damage than Young Stomach. Hong, Hua; Kim, Eun-Hee; Lee, Ho; Kim, Yoon; Lee, Jong; Hahm, Ki // Digestive Diseases & Sciences;Jan2013, Vol. 58 Issue 1, p61 

    Background/Aims: Detailed underlying changes have never been explored to explain how old stomach is more susceptible to non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastric damage than young stomach, although presumptively speculated as weakened mucosal defense system as well as...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics