Effect of nonsteroidal antiinfammatory drugs on lipoxygenase and cyclooxygenase activities on human colon segments from patients with neoplasia.

Effect of nonsteroidal antiinfammatory drugs on lipoxygenase and cyclooxyge nase activities on human colon segments from patients with neoplasia. Lysin e clonixinate (LC) is a nonsteroidal anti-inflammatory drug (NSAID) with go od gastrointestinal tolerance. Treatment with LC at levels equivalent to th ose found in plasma following therapeutic doses resulted in significant inh ibition of both cyclooxygenase 2 (COX-2) and production of 5 hydroxy-eicosa tetraeonic acid (5-HETE) and slightly affected levels of cyclooxygenase 1 ( COX-1) in in vitro studies carried out on human tissues. This study deals w ith the in vivo effect of the drug on human colon segments. Experiment 1: F ive patients about to undergo hemicholechtomy due to colon neoplasia were t reated preoperatively with a continuous infusion of LC, to achieve a steady -state concentration between 4 and 6 mg/ml. Human colon segments from the f ive patients and from another five control patients receiving no treatment with [C-14]-arachidonic acid were incubated. Human colon segments treated w ith LC showed significant inhibition of PGE(2), the only prostaglandin (PG) synthesised by the tissue, as well as of 5-HETE. Experiment 2: Fifteen pat ients received an i.v. bolus of LC 100 mg (n1=5); LC 200mg (n2=5) or indome thacin (INDO) 50 mg (n3=5). Both doses of LC showed greater inhibition of P GE 2 synthesis than the INDO bolus. Both NSAIDs studied proved to have diff erent effects on the production of 5-HETE; while treatment with LC elicited significant Inhibition, levels with INDO remained unchanged. Western blott ing analysis showed expression of both COX isoforms in colon segments, COX- 2 levels being 20% higher. Both types of in vivo studies conducted continuo us infusion and i.v, bolus, revealed that LC exerted significant inhibition of basal synthesis of PGE2 and 5-HETE.