Celecoxib use and circulating oxylipins in a colon polyp prevention trial.

Drugs that inhibit cyclooxygenase (COX)-2 and the metabolism of arachidonic acid (ARA) to prostaglandin E2 are potent anti-inflammatory agents used widely in the treatment of joint and muscle pain. Despite their benefits, daily use of these drugs has been associated with hypertension, cardiovascular and gastrointestinal toxicities. It is now recognized that ARA is metabolized to a number of bioactive oxygenated lipids (oxylipins) by cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP450) enzymes. Currently, the contribution of individual variability in ARA metabolism in response to the COX-2 inhibitors and potential adverse effects remains poorly understood. Using patient samples from the randomized, placebo-controlled phase III selenium/celecoxib (Sel/Cel) trial for the prevention of colorectal adenomatous polyps, we analyzed plasma concentrations of 74 oxylipins in a subset of participants who received celecoxib (n = 90) or placebo (n = 95). We assessed the effect of celecoxib (with and without low dose aspirin) on circulating oxylipins and systolic blood pressure (SBP). Individual CYP450- and LOX- but not COX-derived metabolites were higher with celecoxib than placebo (P<0.05) and differences were greater among non-aspirin users. LOX derived 5- and 8-HETE were elevated with celecoxib and positively associated with systolic blood pressure (P = 0.011 and P = 0.019 respectively). 20-HETE, a prohypertensive androgen-sensitive CYP450 metabolite was higher with celecoxib absent aspirin and was positively associated with SBP in men (P = 0.040) but not women. Independent of celecoxib or aspirin, LOX derived metabolites from ARA were strongly associated with SBP including 5- and 8-HETE. These findings support oxylipins, particularly the ARA LOX-derived, in blood pressure control and indicate that pharmacologic inhibition of COX-2 has effects on LOX and CYP450 ARA metabolism that contribute to hypertension in some patients.

A three-stage treatment system for highly polluted urban road runoff.

A three-stage treatment device for polluted urban road runoff was installed and tested at a highly trafficked urban road over a period of one year. In the first stage coarse material and particles from the runoff are removed by a special gutter system. The second stage eliminates particles using a hydrodynamic separator. In the third stage dissolved pollutants are adsorbed in a filter unit with lignite as filter material. Twenty-four rain events were sampled over the one year period and analyzed for dissolved and particulate copper (Cu), zinc (Zn), lead (Pb), suspended solids (SS), total organic carbon (TOC), sodium (Na), and pH value. The treatment system was able to safely retain all relevant pollutants during the investigated period, except Na. In the effluent of the treatment device Pb could never be detected, values measured for Zn were in the range of the detection limit. Cu, the element most frequently detected in the effluent, never exceeded the critical value of 50 µg/L set by the German Federal Soil Protection Act and Ordinance. The median Cu concentration in the effluent of the treatment system was 8.13 µg/L. The treatment system proved to be very effective. Highly polluted road runoff can be purified by the system to an extent that no contamination risk for soil and groundwater remains when infiltrated into the soil.