Document Detail


Low direct cytotoxicity of nabumetone on gastric mucosal cells.
MedLine Citation:
PMID:  16133963     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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
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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    
Affiliation:
Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Japan.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Animals
Anti-Inflammatory Agents, Non-Steroidal / administration & dosage,  adverse effects*,  pharmacology*
Butanones / administration & dosage,  adverse effects*,  pharmacology*
Cell Culture Techniques
Cell Membrane Permeability
Erythrocytes
Gastric Mucosa / cytology,  drug effects*,  pathology*
Guinea Pigs
Hemolysis
Pyrazoles / adverse effects,  pharmacology
Rats
Severity of Illness Index
Sulfonamides / adverse effects,  pharmacology
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Butanones; 0/Pyrazoles; 0/Sulfonamides; 169590-42-5/celecoxib; 42924-53-8/nabumetone

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