Selective inhibition of human TNF-alpha action by flecainide acetate, an antiarrhythmic drug.

S. Nojima, Hirotsugu Kobuchi, T. Saibara, T. Yasuda, K. Utsumi

Research output: Contribution to journalArticle

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Abstract

It is now generally accepted that human tumor necrosis factor-alpha (hTNF-alpha) affects not only tumor cells but also normal cells, providing critical tissue damage. hTNF-alpha also enhanced the response of polymorphonuclear neutrophils (PMN) by its priming action and resulted in the increased generation of active oxygen which in turn may be responsible for the tissue injury. Seeking a conventional drug to attenuate the cytolytic activity of tumor necrosis factor (TNF-alpha) and thereby prevent excessive tissue injury, we focused on the cytolytic action of hTNF-alpha against L929 cells, which are sensitive to TNF-alpha, and found that flecainide acetate [N-(2-piperidylmethyl) 1,5-bis-(2,2,2-trifluoroethoxy) benzamide acetate] inhibited specifically the cytolytic action of hTNF-alpha against L929 cells. Flecainide acetate also specifically inhibited the priming action of hTNF-alpha which enhance the formylmethionyl-leucyl-phenylalanine (FMLP)-induced receptor-mediated superoxide (O.2-) generation of human peripheral polymorphonuclear neutrophils (hPMN). The ID50 values for hTNF-alpha induced cytotoxicity in L929 cells and hTNF-alpha primed FMLP-induced O.2- generation of hPMN were 30 and 50-60 microM, respectively. However, the drug does not inhibit the FMLP- or phorbol myristate acetate (PMA)-induced O.2- generation of nonprimed hPMN and has a weak cytotoxic effect on L929 cells. From these results, it is concluded that flecainide acetate suppressed specifically the action of hTNF-alpha.

Original languageEnglish
Pages (from-to)77-89
Number of pages13
JournalPhysiological Chemistry and Physics and Medical NMR
Volume27
Issue number2
Publication statusPublished - 1995

Fingerprint

Flecainide
Anti-Arrhythmia Agents
Tumor Necrosis Factor-alpha
N-Formylmethionine Leucyl-Phenylalanine
Neutrophils
Tissue
human TNF protein
Wounds and Injuries
Tetradecanoylphorbol Acetate
Cytotoxicity
Superoxides
Pharmaceutical Preparations
Tumors
Reactive Oxygen Species
Acetates

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Biophysics
  • Physiology
  • Physiology (medical)
  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology

Cite this

Selective inhibition of human TNF-alpha action by flecainide acetate, an antiarrhythmic drug. / Nojima, S.; Kobuchi, Hirotsugu; Saibara, T.; Yasuda, T.; Utsumi, K.

In: Physiological Chemistry and Physics and Medical NMR, Vol. 27, No. 2, 1995, p. 77-89.

Research output: Contribution to journalArticle

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