Identification of a unique nsaid, fluoro-loxoprofen with gastroprotective activity

Shintaro Suemasu, Naoki Yamakawa, Tomoaki Ishihara, Teita Asano, Kayoko Tahara, Ken Ichiro Tanaka, Hirofumi Matsui, Yoshinari Okamoto, Masami Otsuka, Koji Takeuchi, Hidekazu Suzuki, Tohru Mizushima

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

We previously proposed that direct cytotoxicity of NSAIDs due to their membrane permeabilization activity, together with their ability to decrease gastric prostaglandin E2, contributes to production of gastric lesions. Compared to loxoprofen (LOX), fluoro-loxoprofen (F-LOX) has much lower membrane permeabilization and gastric ulcerogenic activities but similar anti-inflammatory activity. In this study, we examined the mechanism for this low ulcerogenic activity in rats. Compared to LOX, the level of gastric mucosal cell death was lower following administration of F-LOX. However, the gastric level of prostaglandin E2 was similar in response to treatment with the two NSAIDs. Oral pre-administration of F-LOX conferred protection against the formation of gastric lesions produced by subsequent administration of LOX and orally administered F-LOX resulted in a higher gastric pH value and mucus content. In the presence of a stimulant of gastric acid secretion, the difference in the ulcerogenic activity of F-LOX and LOX was less apparent. Furthermore, an increase in the mucus was observed in gastric cells cultured in the presence of F-LOX in a manner dependent of increase in the cellular level of cAMP. These results suggest that low ulcerogenic activity of F-LOX involves its both low direct cytotoxicity and protective effect against the development of gastric lesions. This protective effect seems to be mediated through an increase in a protective factor (mucus) and a decrease in an aggressive factor (acid).

Original languageEnglish
Pages (from-to)1470-1481
Number of pages12
JournalBiochemical Pharmacology
Volume84
Issue number11
DOIs
Publication statusPublished - 2012 Dec 1

Fingerprint

Stomach
Mucus
Non-Steroidal Anti-Inflammatory Agents
Cytotoxicity
Dinoprostone
Membranes
Acids
Cell death
fluoro-loxoprofen
Gastric Acid
Rats
Anti-Inflammatory Agents
Oral Administration
Cultured Cells
Cell Death
loxoprofen

Keywords

  • Gastrointestinal complications
  • Mucus
  • NSAIDs

ASJC Scopus subject areas

  • Pharmacology
  • Biochemistry

Cite this

Suemasu, S., Yamakawa, N., Ishihara, T., Asano, T., Tahara, K., Tanaka, K. I., ... Mizushima, T. (2012). Identification of a unique nsaid, fluoro-loxoprofen with gastroprotective activity. Biochemical Pharmacology, 84(11), 1470-1481. https://doi.org/10.1016/j.bcp.2012.09.016

Identification of a unique nsaid, fluoro-loxoprofen with gastroprotective activity. / Suemasu, Shintaro; Yamakawa, Naoki; Ishihara, Tomoaki; Asano, Teita; Tahara, Kayoko; Tanaka, Ken Ichiro; Matsui, Hirofumi; Okamoto, Yoshinari; Otsuka, Masami; Takeuchi, Koji; Suzuki, Hidekazu; Mizushima, Tohru.

In: Biochemical Pharmacology, Vol. 84, No. 11, 01.12.2012, p. 1470-1481.

Research output: Contribution to journalArticle

Suemasu, S, Yamakawa, N, Ishihara, T, Asano, T, Tahara, K, Tanaka, KI, Matsui, H, Okamoto, Y, Otsuka, M, Takeuchi, K, Suzuki, H & Mizushima, T 2012, 'Identification of a unique nsaid, fluoro-loxoprofen with gastroprotective activity', Biochemical Pharmacology, vol. 84, no. 11, pp. 1470-1481. https://doi.org/10.1016/j.bcp.2012.09.016
Suemasu S, Yamakawa N, Ishihara T, Asano T, Tahara K, Tanaka KI et al. Identification of a unique nsaid, fluoro-loxoprofen with gastroprotective activity. Biochemical Pharmacology. 2012 Dec 1;84(11):1470-1481. https://doi.org/10.1016/j.bcp.2012.09.016
Suemasu, Shintaro ; Yamakawa, Naoki ; Ishihara, Tomoaki ; Asano, Teita ; Tahara, Kayoko ; Tanaka, Ken Ichiro ; Matsui, Hirofumi ; Okamoto, Yoshinari ; Otsuka, Masami ; Takeuchi, Koji ; Suzuki, Hidekazu ; Mizushima, Tohru. / Identification of a unique nsaid, fluoro-loxoprofen with gastroprotective activity. In: Biochemical Pharmacology. 2012 ; Vol. 84, No. 11. pp. 1470-1481.
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