- Mohebati A, Milne GL, Zhou XK, Duffield-Lillico AJ, Boyle JO, Knutson A, Bosworth BP, Kingsley PJ, Marnett LJ, Brown PH, Akpa EG, Szabo E, Dannenberg AJ. Effect of zileuton and celecoxib on urinary LTE4 and PGE-M levels in smokers. Cancer prevention research (Philadelphia, Pa.). 2013 Jul;6(7). 646-55. PMID: 23682075 [PubMed]. PMCID: PMC3707304. NIHMSID: NIHMS479713.
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 E4 (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-M and LTE4 levels in smokers. Treatment with zileuton led to an 18% decrease in PGE-M levels (P = 0.03); the combination of zileuton and celecoxib led to a 62% reduction in PGE-M levels (P