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

研究成果: Article査読

30 被引用数 (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.

ジャーナルBiological and Pharmaceutical Bulletin
出版ステータスPublished - 2010 3月

ASJC Scopus subject areas

  • 薬理学
  • 薬科学


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