Mechanisms of active oxygen species reduction by non-steroidal anti-inflammatory drugs

Int J Biochem Cell Biol. 1997 Mar;29(3):437-46. doi: 10.1016/s1357-2725(96)00144-6.

Abstract

Many forms of active oxygen have been suggested to participate in the course of inflammation. Anti-inflammatory drugs have been considered to function as active oxygen inhibitors. However, detailed mechanisms for such inhibitory activity remain unclear because of little well established methods to study inhibitory effect of anti-inflammatory drugs on active oxygen species. In this report, the author investigated four non-steroidal anti-inflammatory drugs, including acetaminophen, sodium salicylate, naproxen and flurbiprofen, their elimination and inhibition ability of active oxygen, using of the electron spin resonance spin-trapping method and the horseradish peroxidase method. In this experiment as active oxygen models, superoxide was evolved from a hypoxanthine-xanthine oxidase reaction system, and hydrogen peroxide by the spontaneous dismutation reaction. The data here show that the amount of superoxide was reduced in the manner of concentration of non-steroidal anti-inflammatory drugs in the reaction. Kinetic studies for these reaction showed that acetaminophen and sodium salicylate reacted with superoxide competitively, whereas naproxen and flurbiprofen did not. Analysis of generation of hydrogen peroxide formed by the spontaneous dismutation of superoxide derived from the reaction system revealed that hydrogen peroxide was increased by acetaminophen and decreased by sodium salicylate, naproxen and flurbiprofen.

MeSH terms

  • Allopurinol / chemistry
  • Allopurinol / metabolism
  • Allopurinol / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / metabolism*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Electron Spin Resonance Spectroscopy / methods
  • Horseradish Peroxidase / analysis
  • Horseradish Peroxidase / chemistry
  • Hydrogen Peroxide / analysis
  • Hydrogen Peroxide / chemistry
  • Hydrogen Peroxide / metabolism
  • Hydroxyl Radical / chemistry
  • Hydroxyl Radical / metabolism
  • Hypoxanthine / chemistry
  • Hypoxanthine / metabolism
  • Kinetics
  • Oxidation-Reduction
  • Reactive Oxygen Species / metabolism*
  • Spectrophotometry / methods
  • Superoxide Dismutase / chemistry
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase / pharmacology
  • Superoxides / metabolism
  • Xanthine Oxidase / chemistry
  • Xanthine Oxidase / drug effects
  • Xanthine Oxidase / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Reactive Oxygen Species
  • Superoxides
  • Hypoxanthine
  • Hydroxyl Radical
  • Allopurinol
  • Hydrogen Peroxide
  • Horseradish Peroxidase
  • Superoxide Dismutase
  • Xanthine Oxidase