Membrane permeabilization by non-steroidal anti-inflammatory drugs

Wataru Tomisato, Ken Ichiro Tanaka, Takashi Katsu, Hiroki Kakuta, Kenji Sasaki, Shinji Tsutsumi, Tatsuya Hoshino, Mayuko Aburaya, Daiwei Li, Tomofusa Tsuchiya, Keitarou Suzuki, Kazumi Yokomizo, Tohru Mizushima

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79 Citations (Scopus)

Abstract

The cytotoxicity of non-steroidal anti-inflammatory drugs (NSAIDs) is involved in the formation of NSAID-induced gastric lesions. The mechanism(s) behind these cytotoxic effects, however, is not well understood. We found here that several NSAIDs tested caused hemolysis when employed at concentrations similar to those that result in cytotoxicity. Moreover, these same NSAIDs were found to directly permeabilize the membranes of calcein-loaded liposomes. Given the similarity in NSAID concentrations for cytotoxic and membrane permeabilization effects, the cytotoxic action of these NSAIDs may be mediated through the permeabilization of biological membranes. Increase in the intracellular Ca 2+ level can lead to cell death. We here found that all of NSAIDs tested increased the intracellular Ca 2+ level at concentrations similar to those that result in cytotoxicity. Based on these results, we consider a possibility that membrane permeabilization by NSAIDs induces cell death through increase in the intracellular Ca 2+ level.

Original languageEnglish
Pages (from-to)1032-1039
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume323
Issue number3
DOIs
Publication statusPublished - Oct 22 2004

Keywords

  • Cytotoxicity
  • Gastric mucosal cells
  • Intracellular Ca level
  • Membrane fluidity
  • Membrane permeabilization
  • NSAIDs

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Tomisato, W., Tanaka, K. I., Katsu, T., Kakuta, H., Sasaki, K., Tsutsumi, S., Hoshino, T., Aburaya, M., Li, D., Tsuchiya, T., Suzuki, K., Yokomizo, K., & Mizushima, T. (2004). Membrane permeabilization by non-steroidal anti-inflammatory drugs. Biochemical and Biophysical Research Communications, 323(3), 1032-1039. https://doi.org/10.1016/j.bbrc.2004.08.205