Effect of zileuton and celecoxib on urinary LTE4 and PGE-M levels in smokers Journal Article
| Authors: | Mohebati, A.; Milne, G. L.; Zhou, X. K.; Duffield-Lillico, A. J.; Boyle, J. O.; Knutson, A.; Bosworth, B. P.; Kingsley, P. J.; Marnett, L. J.; Brown, P. H.; Akpa, E. G.; Szabo, E.; Dannenberg, A. J. |
| Article Title: | Effect of zileuton and celecoxib on urinary LTE4 and PGE-M levels in smokers |
| Abstract: | COX-2 and 5-lipoxygenase (5-LO) use arachidonic acid for the synthesis of eicosanoids that have been implicated in carcinogenesis and cardiovascular disease. The ability of celecoxib, a selective COX-2 inhibitor, to redirect arachidonic acid into the 5-LO pathway can potentially reduce its efficacy as a chemopreventive agent and increase the risk of cardiovascular complications. Levels of urinary prostaglandin E metabolite (PGE-M) and leukotriene E 4 (LTE4), biomarkers of the COX and 5-LO pathways, are elevated in smokers. Here, we investigated the effects of zileuton, a 5-LO inhibitor, versus zileuton and celecoxib for 6±1 days on urinary PGE-Mand LTE4 levels in smokers. Treatment with zileuton led to an18% decrease in PGE-M levels (P = 0.03); the combination of zileuton and celecoxib led to a 62% reduction in PGE-M levels (P < 0.001). Levels of LTE4 decreased by61%in subjects treated with zileuton alone (P < 0.001) and were unaffected by the addition of celecoxib. Although zileuton use was associated with a small overall decrease in PGE-M levels, increased PGE-M levels were found in a subset (19 of 52) of subjects. Notably, the addition of celecoxib to the 5-LO inhibitor protected against the increase in urinary PGE-M levels (P=0.03). In conclusion, zileuton was an effective inhibitor of 5-LO activity resulting in marked suppression of urinary LTE4 levels and possible redirection of arachidonic acid into the COX-2 pathway in a subset of subjects. Combining celecoxib and zileuton was associated with inhibition of both the COX-2 and 5-LO pathways manifested as reduced levels of urinary PGE-M and LTE4. |
| Journal Title: | Cancer Prevention Research |
| Volume: | 6 |
| Issue: | 7 |
| ISSN: | 1940-6207 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2013-07-01 |
| Start Page: | 646 |
| End Page: | 655 |
| Language: | English |
| DOI: | 10.1158/1940-6207.capr-13-0083 |
| PROVIDER: | scopus |
| PMCID: | PMC3707304 |
| PUBMED: | 23682075 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 August 2013" - "Source: Scopus" |
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