Role of direct cytotoxic effects of NSAIDs in the induction of gastric lesions

Wataru Tomisato, Shinji Tsutsumi, Tatsuya Hoshino, Hyun Jung Hwang, Mitsunobu Mio, Tomofusa Tsuchiya, Tohru Mizushima

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

A major clinical problem encountered with the use of non-steroidal anti-inflammatory drugs (NSAIDs), is gastrointestinal complications. We previously reported that NSAIDs induce both necrosis and apoptosis in vitro. We here examined the cyclooxygenase (COX) dependency of this cytotoxic effect of NSAIDs and its involvement in NSAID-induced gastric lesions. Necrosis and apoptosis by NSAIDs was observed with all selective COX-2 inhibitors except rofecoxib and was not inhibited by exogenously added prostaglandin E 2, suggesting that cytotoxicity of NSAIDs seems to be independent of the inhibition of COX. Intravenously administered indomethacin, which completely inhibited COX activity at gastric mucosa, did not produce gastric lesions. Orally administered selective COX-2 inhibitors, which did not inhibit COX at gastric mucosa, also did not produce gastric lesions. Interestingly, a combination of the oral administration of each of all selective COX-2 inhibitors except rofecoxib with the intravenous administration of indomethacin clearly produced gastric lesions. These results suggest that in addition to COX inhibition by NSAIDs, direct cytotoxicity of NSAIDs may be involved in NSAID-induced gastric lesions.

Original languageEnglish
Pages (from-to)575-585
Number of pages11
JournalBiochemical Pharmacology
Volume67
Issue number3
DOIs
Publication statusPublished - 2004 Feb 1
Externally publishedYes

Fingerprint

Stomach
Anti-Inflammatory Agents
Prostaglandin-Endoperoxide Synthases
Pharmaceutical Preparations
Gastrointestinal Agents
Cyclooxygenase 2 Inhibitors
Cytotoxicity
Gastric Mucosa
Indomethacin
Necrosis
Apoptosis
Prostaglandins E
Intravenous Administration
Oral Administration

Keywords

  • Cyclooxygenase
  • Direct cytotoxicity
  • Gastric lesions
  • NSAIDs
  • Prostaglandin E
  • Selective cyclooxygenase-2 inhibitors

ASJC Scopus subject areas

  • Pharmacology

Cite this

Tomisato, W., Tsutsumi, S., Hoshino, T., Hwang, H. J., Mio, M., Tsuchiya, T., & Mizushima, T. (2004). Role of direct cytotoxic effects of NSAIDs in the induction of gastric lesions. Biochemical Pharmacology, 67(3), 575-585. https://doi.org/10.1016/j.bcp.2003.09.020

Role of direct cytotoxic effects of NSAIDs in the induction of gastric lesions. / Tomisato, Wataru; Tsutsumi, Shinji; Hoshino, Tatsuya; Hwang, Hyun Jung; Mio, Mitsunobu; Tsuchiya, Tomofusa; Mizushima, Tohru.

In: Biochemical Pharmacology, Vol. 67, No. 3, 01.02.2004, p. 575-585.

Research output: Contribution to journalArticle

Tomisato, W, Tsutsumi, S, Hoshino, T, Hwang, HJ, Mio, M, Tsuchiya, T & Mizushima, T 2004, 'Role of direct cytotoxic effects of NSAIDs in the induction of gastric lesions', Biochemical Pharmacology, vol. 67, no. 3, pp. 575-585. https://doi.org/10.1016/j.bcp.2003.09.020
Tomisato W, Tsutsumi S, Hoshino T, Hwang HJ, Mio M, Tsuchiya T et al. Role of direct cytotoxic effects of NSAIDs in the induction of gastric lesions. Biochemical Pharmacology. 2004 Feb 1;67(3):575-585. https://doi.org/10.1016/j.bcp.2003.09.020
Tomisato, Wataru ; Tsutsumi, Shinji ; Hoshino, Tatsuya ; Hwang, Hyun Jung ; Mio, Mitsunobu ; Tsuchiya, Tomofusa ; Mizushima, Tohru. / Role of direct cytotoxic effects of NSAIDs in the induction of gastric lesions. In: Biochemical Pharmacology. 2004 ; Vol. 67, No. 3. pp. 575-585.
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