Agents and Actions

, Volume 39, Issue 1–2, pp 49–58 | Cite as

Is aspirin a prodrug for antioxidant and cytokine-modulating oxymetabolites

  • D. R. Haynes
  • P. F. A. Wright
  • S. J. Gadd
  • M. W. Whitehouse
  • B. Vernon-Roberts
Inflammation

Abstract

Aspirin and salicylate are transformed by stimulated human polymorphonuclear leucocytes (PMN), likely to be found at inflammatory sites, into both 2,3- and 2,5-dihydroxybenzoates (DHB). These DHB inhibit both the production of hydrogen peroxide by stimulated human PMN and prostaglandin (PG) E2 by activated rat macrophages. In contrast, DHB stimulated production of interleukin (IL)-1 and tumour necrosis factor (TNF) but inhibited IL-6 production by rat macrophages. These effects were probably a consequence of PGE2 inhibition. Gentisate (2,5-DHB) and homogentisate (a tyrosine metabolite) inhibited the lymphoproliferative action of IL-1. Some related phenols, e.g. 5-aminosalicylate, inhibited H2O2 production but had little effect on PGE2 production.

These findings suggest that the local synthesis of DHB may contribute to the overall anti-inflammatory activity of salicylate, which (unlike aspirin) has little direct effect on PG production.

Keywords

Aspirin PGE2 Salicylate Gentisate H2O2 Production 

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Copyright information

© Birkhäuser Verlag 1993

Authors and Affiliations

  • D. R. Haynes
    • 1
  • P. F. A. Wright
    • 2
  • S. J. Gadd
    • 1
  • M. W. Whitehouse
    • 1
    • 3
  • B. Vernon-Roberts
    • 1
    • 3
  1. 1.Department of PathologyUniversity of Adelaide
  2. 2.Key Centre for Applied and Nutritional ToxicologyRoyal Melbourne Institute of TechnologyMelbourneAustralia
  3. 3.Division of Tissue PathologyInstitute of Medical and Veterinary ScienceAdelaide

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