Neuroprotective effects of non-steroidal anti-inflammatory drugs by direct scavenging of nitric oxide radicals

Masato Asanuma, Sakiko Nishibayashi-Asanuma, Ikuko Miyazaki, Masahiro Kohno, Norio Ogawa

Research output: Contribution to journalArticle

167 Citations (Scopus)

Abstract

Recently, it has been reported that inflammatory processes are associated with the pathophysiology of Alzheimer's disease and that treatment of non-steroidal anti-inflammatory drugs reduce the risk for Alzheimer's disease. In the present study, we examined nitric oxide radical quenching activity of non-steroidal anti-inflammatory drugs and steroidal drugs using our established direct in vitro nitric oxide radical detecting system by electron spin resonance spectrometry. The non-steroidal anti-inflammatory drugs, aspirin, mefenamic acid, indomethacin and ketoprofen directly and dose-dependently scavenged generated nitric oxide radicals. In experiments of nitric oxide radical donor, NOC18-induced neuronal damage, these four non-steroidal drugs significantly prevented the NOC18-induced reduction of cell viability and apoptotic nuclear changes in neuronal cells without affecting the induction of inducible nitric oxide synthase-like immunoreactivity. However, ibuprofen, naproxen or steroidal drugs, which had less or no scavenging effects in vitro, showed almost no protective effects against NOC18-induced cell toxicity. These results suggest that the protective effects of the former four non-steroidal anti-inflammatory drugs against apoptosis might be mainly due to their direct nitric oxide radical scavenging activities in neuronal cells. These direct NO quenching activities represent novel effects of nonsteroidal anti-inflammatory drugs. Our findings identified novel pharmacological mechanisms of these drugs to exert not only their anti-inflammatory, analgesic, antipyretic activities but also neuroprotective activities against neurodegeneration.

Original languageEnglish
Pages (from-to)1895-1904
Number of pages10
JournalJournal of Neurochemistry
Volume76
Issue number6
DOIs
Publication statusPublished - 2001

Keywords

  • Aspirin
  • Indomethacin
  • Ketoprofen
  • Mefenamic acid
  • Nitric oxide
  • Non-steroidal anti-inflammatory drugs

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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