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

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25 Citations (Scopus)

Abstract

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
Volume33
Issue number3
DOIs
Publication statusPublished - 2010 Mar

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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  • Cite this

    Yamakawa, N., Suemasu, S., Kimoto, A., Arai, Y., Ishihara, T., Yokomizo, K., Okamoto, Y., Otsuka, M., Tanaka, K. I., & Mizushima, T. (2010). Low direct cytotoxicity of loxoprofen on gastric mucosal cells. Biological and Pharmaceutical Bulletin, 33(3), 398-403. https://doi.org/10.1248/bpb.33.398