Levels of prostaglandin E metabolite and leukotriene E(4) are increased in the urine of smokers: Evidence that celecoxib shunts arachidonic acid into the 5-lipoxygenase pathway Journal Article
| Authors: | Duffield-Lillico, A. J.; Boyle, J. O.; Xi, K. Z.; Ghosh, A.; Butala, G. S.; Subbaramaiah, K.; Newman, R. A.; Morrow, J. D.; Milne, G. L.; Dannenberg, A. J. |
| Article Title: | Levels of prostaglandin E metabolite and leukotriene E(4) are increased in the urine of smokers: Evidence that celecoxib shunts arachidonic acid into the 5-lipoxygenase pathway |
| 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. ©2009 American Association for Cancer Research. |
| Keywords: | signal transduction; controlled study; major clinical study; clinical trial; drug withdrawal; recommended drug dose; treatment duration; comparative study; mass spectrometry; metabolism; controlled clinical trial; inflammation; smoking; drug effect; pneumonia; celecoxib; cyclooxygenase 2 inhibitor; pyrazole derivative; sulfonamide; cardiovascular disease; chemically induced disorder; cyclooxygenase 2 inhibitors; pyrazoles; sulfonamides; cyclooxygenase 2; arthritis; urine; arachidonate 5 lipoxygenase; drug blood level; arachidonic acid; leukotriene e4; prostaglandin e; absence of side effects; concentration (parameters); liquid chromatography; prostaglandin blood level; urine level; arachidonate 5-lipoxygenase; prostaglandins e |
| Journal Title: | Cancer Prevention Research |
| Volume: | 2 |
| Issue: | 4 |
| ISSN: | 1940-6207 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2009-04-01 |
| Start Page: | 322 |
| End Page: | 329 |
| Language: | English |
| DOI: | 10.1158/1940-6207.capr-09-0005 |
| PUBMED: | 19336727 |
| PROVIDER: | scopus |
| PMCID: | PMC2745265 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 9" - "Export Date: 30 November 2010" - "Source: Scopus" |
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