Effect of nonsteroidal antiinflammatory drugs on colonic lipoxygenase and cyclooxygenase activities from patients with colonic neoplasia

• Published in: Medicina (Buenos Aires) Vol. 61; no. 5 Pt 1; p. 566
• Main Authors: Di Girolamo, G, Franchi, A, De Los Santos, A R, Martí, M L, Farina, M, Fernández de Gimeno, M A
• Format: Journal Article
• Language: Spanish
• Published: Argentina 2001
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Arachidonate 5-Lipoxygenase - biosynthesis; Arachidonate 5-Lipoxygenase - drug effects; Clonixin - analogs & derivatives; Clonixin - pharmacology; Colon - drug effects; Colon - enzymology; Colonic Neoplasms - enzymology; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - pharmacology; Dinoprostone - biosynthesis; Humans; Hydroxyeicosatetraenoic Acids - biosynthesis; Indomethacin - pharmacology; Isoenzymes - metabolism; Lipoxygenase Inhibitors - pharmacology; Lysine - analogs & derivatives; Lysine - pharmacology; Membrane Proteins; Prostaglandin-Endoperoxide Synthases - biosynthesis; Prostaglandin-Endoperoxide Synthases - drug effects; Prostaglandin-Endoperoxide Synthases - metabolism
• ISSN: 0025-7680

Lysine clonixinate (LC) is a nonsteroidal anti-inflammatory drug (NSAID) with good gastrointestinal tolerance. Treatment with LC at levels equivalent to those found in plasma following therapeutic doses resulted in significant inhibition of both cyclooxygenase 2 (COX-2) and production of 5 hydroxy-eicosatetraeonic acid (5-HETE) and slightly affected levels of cyclooxygenase 1 (COX-1) in in vitro studies carried out on human tissues. This study deals with the in vivo effect of the drug on human colon segments. Experiment 1: Five patients about to undergo hemicholectomy due to colon neoplasia were treated preoperatively with a continuous infusion of LC, to achieve a steady-state concentration between 4 and 6 mg/ml. Human colon segments from the five patients and from another five control patients receiving no treatment with [14C]-arachidonic acid were incubated. Human colon segments treated with LC showed significant inhibition of PGE2, the only prostaglandin (PG) synthesised by the tissue, as well as of 5-HETE. Experiment 2: Fifteen patients received an i.v. bolus of LC 100 mg (n1 = 5); LC 200 mg (n2 = 5) or indomethacin (INDO) 50 mg (n3 = 5). Both doses of LC showed greater inhibition of PGE2 synthesis than the INDO bolus. Both NSAIDs studied proved to have different effects on the production of 5-HETE; while treatment with LC elicited significant inhibition, levels with INDO remained unchanged. Western blotting analysis showed expression of both COX isoforms in colon segments, COX-2 levels being 20% higher. Both types of in vivo studies conducted continuous infusion and i.v. bolus, revealed that LC exerted significant inhibition of basal synthesis of PGE2 and 5-HETE.