Document Detail

Low direct cytotoxicity of nabumetone on gastric mucosal cells.
MedLine Citation:
PMID:  16133963     Owner:  NLM     Status:  MEDLINE    
Prodrugs of non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for clinical purposes because they are not harmful to the gastrointestinal mucosa. We recently showed that NSAIDs have direct cytotoxicity in NSAID-induced gastric lesions. We show here that under conditions where the NSAIDs indomethacin and celecoxib clearly induce cell death, an NSAID prodrug, nabumetone, and its active metabolite 6-methoxy-2-naphthylacetic acid (6MNA), did not have such effects. Moreover, nabumetone and 6MNA exhibited much lower membrane permeabilizing activities than did indomethacin and celecoxib. We recently reported that when an orally administered NSAID was used in combination with a low dose of intravenously administered indomethacin, the severity of gastric lesions produced in rats depended on the cytotoxicity of the orally administered NSAID. Using a similar protocol, we show here that gastric lesions were produced when the orally administered NSAID was celecoxib, but not when nabumetone was used. We thus propose that the low direct cytotoxicity of nabumetone observed in vitro is maintained in vivo, and that the use of nabumetone does not harm the gastric mucosa.
Yasuhiro Arai; Ken-Ichiro Tanaka; Hironori Ushijima; Wataru Tomisato; Shinji Tsutsumi; Mayuko Aburaya; Tatsuya Hoshino; Kazumi Yokomizo; Keitarou Suzuki; Takashi Katsu; Tomofusa Tsuchiya; Tohru Mizushima
Related Documents :
10632653 - A retrospective study of the usefulness of acid secretory testing.
19166613 - Fatty acid composition of subcutaneous adipose tissue and gastric mucosa: is there a re...
7521313 - A multicenter randomized controlled dose study of ursodeoxycholic acid for chronic hepa...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Digestive diseases and sciences     Volume:  50     ISSN:  0163-2116     ISO Abbreviation:  Dig. Dis. Sci.     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-08-31     Completed Date:  2005-09-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7902782     Medline TA:  Dig Dis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1641-6     Citation Subset:  AIM; IM    
Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Japan.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Administration, Oral
Anti-Inflammatory Agents, Non-Steroidal / administration & dosage,  adverse effects*,  pharmacology*
Butanones / administration & dosage,  adverse effects*,  pharmacology*
Cell Culture Techniques
Cell Membrane Permeability
Gastric Mucosa / cytology,  drug effects*,  pathology*
Guinea Pigs
Pyrazoles / adverse effects,  pharmacology
Severity of Illness Index
Sulfonamides / adverse effects,  pharmacology
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Butanones; 0/Pyrazoles; 0/Sulfonamides; 169590-42-5/celecoxib; 42924-53-8/nabumetone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Nitro-arginine methyl ester, a non-selective inhibitor of nitric oxide synthase reduces ibuprofen-in...
Next Document:  Relationships between gastric accommodation and gastrointestinal sensations in healthy volunteers. A...