Low direct cytotoxicity of loxoprofen on gastric mucosal cells

Naoki Yamakawa, Shintaro Suemasu, Ayumi Kimoto, Yasuhiro Arai, Tomoaki Ishihara, Kazumi Yokomizo, Yoshinari Okamoto, Masami Otsuka, Ken Ichiro Tanaka, Tohru Mizushima

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)


Pro-drugs of non-steroidal anti-inflammatory drugs (NSAIDs), such as loxoprofen are widely used for clinical purposes because they are not so harmful to the gastrointestinal mucosa. We recently showed that NSAIDs such as indomethacin and celecoxib have direct cytotoxicity (ability to induce necrosis and apoptosis in gastric mucosal cells) due to their membrane permeabilizing activities, which is involved in NSAID-induced gastric lesions. We show here that under conditions where indomethacin and celecoxib clearly induce necrosis and apoptosis, loxoprofen and its active metabolite loxoprofen-OH, do not have such effects in primary culture of guinea pig gastric mucosal cells. Loxoprofen and loxoprofen-OH induced apoptosis more effectively in cultured human gastric cancer cells than in the primary culture. Loxoprofen and loxoprofen-OH exhibited much lower membrane permeabilizing activities than did indomethacin and celecoxib. We thus consider that the low direct cytotoxicity of loxoprofen observed in vitro is involved in its relative safety on production of gastric lesions in clinical situation.

Original languageEnglish
Pages (from-to)398-403
Number of pages6
JournalBiological and Pharmaceutical Bulletin
Issue number3
Publication statusPublished - 2010 Mar


  • Gastric lesion
  • Gastric mucosal cell
  • Loxoprofen
  • Membrane permeabilization

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science


Dive into the research topics of 'Low direct cytotoxicity of loxoprofen on gastric mucosal cells'. Together they form a unique fingerprint.

Cite this