Low direct cytotoxicity and cytoprotective effects of nitric oxide releasing indomethacin.

Abstract

Nitric oxide (NO) releasing non-steroidal anti-inflammatory drugs (NSAIDs) have shown a marked reduction of gastrointestinal side effects and we here examined the cytotoxicity of NCX 530 (NO-indomethacin). Under conditions where indomethacin clearly induced both necrosis and apoptosis, NCX 530 induced neither. NCX 530 protected cells from celecoxib-induced necrosis and apoptosis. NCX 530 partially suppressed celecoxib-dependent membrane permeabilization and an inhibitor for guanylate cyclase suppressed the cytoprotective effect of NCX 530 against celecoxib. In vivo, NCX 530 alone produced fewer gastric lesions in rats than did indomethacin. A combination of the oral administration of celecoxib together with the intraperitoneal administration of indomethacin, but not of NCX 530, clearly resulted in the production of gastric lesions. The low direct cytotoxicity and the cytoprotective effect of NCX 530 observed in vitro may also act in vivo, thus ensuring that NCX 530 is safe for use on the gastric mucosa.

• Authors: Wataru Tomisato, Ken-Ichiro Tanaka, Shinji Tsutsumi, Tatsuya Hoshino, Kazumi Yokomizo, Keitarou Suzuki, Takashi Katsu, Tohru Mizushima, Tohru Mizushima
• Journal: Digestive diseases and sciences (Dig Dis Sci) Vol. 50 Issue 10 Pg. 1927-37 (Oct 2005) ISSN: 0163-2116 [Print] United States
• PMID: 16187199 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 1-(4-chlorobenzoyl)-5-methoxy-2-1H-indole-3-acetic acid 3-(nitrooxymethyl)phenyl ester
• Acetates
• Anti-Inflammatory Agents, Non-Steroidal
• Indoles
• Indomethacin

Topics

• Acetates (administration & dosage, pharmacology)
• Administration, Oral
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, pharmacology)
• Cell Culture Techniques
• Cell Death (drug effects)
• Cell Survival (drug effects)
• Cytoprotection (drug effects)
• Gastric Mucosa (cytology, drug effects)
• Guinea Pigs
• Indoles (administration & dosage, pharmacology)
• Indomethacin (administration & dosage, pharmacology)
• Male
• Rats
• Rats, Wistar
• Stomach (drug effects)