Levels of prostaglandin E metabolite and leukotriene E4 are increased in the urine of smokers: Evidence that celecoxib shunts arachidonic acid into the 5-lipoxygenase pathway Academic Article uri icon

Overview

MeSH Major

  • Arachidonate 5-Lipoxygenase
  • Cyclooxygenase 2 Inhibitors
  • Leukotriene E4
  • Prostaglandins E
  • Pyrazoles
  • Smoking
  • Sulfonamides

abstract

  • Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LO) play a role in inflammation and carcinogenesis. Biomarkers that reflect tobacco smoke-induced tissue injury are needed. In this study, levels of urinary prostaglandin E metabolite (PGE-M) and leukotriene E(4) (LTE(4)), biomarkers of the COX and 5-LO pathways, were compared in never smokers, former smokers, and current smokers. The effects of celecoxib, a selective COX-2 inhibitor, on levels of PGE-M and LTE(4) were determined. Baseline levels of PGE-M and LTE(4) were positively associated with smoking status; levels of PGE-M and LTE(4) were higher in current versus never smokers. Treatment with 200 mg celecoxib twice daily for 6 +/- 1 days led to a reduction in urinary PGE-M levels in all groups but exhibited the greatest effect among subjects with high baseline PGE-M levels. Thus, high baseline PGE-M levels in smokers reflected increased COX-2 activity. In individuals with high baseline PGE-M levels, treatment with celecoxib led to a significant increase in levels of urinary LTE(4), an effect that was not found in individuals with low baseline PGE-M levels. In conclusion, increased levels of urinary PGE-M and LTE(4) were found in human smokers, a result that may reflect subclinical lung inflammation. In individuals with high baseline levels of PGE-M (elevated COX-2 activity), celecoxib administration shunted arachidonic acid into the proinflammatory 5-LO pathway. Because 5-LO activity and LTE(4) have been suggested to play a role in cardiovascular disease, these results may help to explain the link between use of COX-2 inhibitors and cardiovascular complications.

publication date

  • April 2009

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2745265

Digital Object Identifier (DOI)

  • 10.1158/1940-6207.CAPR-09-0005

PubMed ID

  • 19336727

Additional Document Info

start page

  • 322

end page

  • 9

volume

  • 2

number

  • 4