Changes of L-Arginine Metabolism in Rat`S Colon Mucosa Under the Conditions of COX/LOX Inhibition and Acute Stress Action

Abstract

Introduction. L-arginine is a semi-essential amino acid and a precursor of many biologically active compounds. Polyamines and NO produced from L-arginine take part in the regulation of biochemical processes in colon mucosa. Emotional stress, nonsteroidal anti-inflammatory drugs (NSAIDs) and their combined action can change the activity of L-arginine metabolizing enzymes. The aim of this study was to investigate the single action of NSAIDs with different mechanisms of action and their combination with acute stress on L-arginine metabolism in colon mucosa of rats. Methods. Animals were divided into 8 groups: control group (1), administration of nonselective, COX-2 selective and dual COX-2/5-LOX inhibitors (groups 2-4), acute stress group (5), administration of same NSAIDs as in groups 2-4 under the conditions of acute stress (groups 6-8). The activity of iNOS, cNOS, arginase, concentration of L-arginine, nitrite and nitrate was measured in colon mucosa. Results. Nonselective COX inhibition by naproxen caused the increase in iNOS and decrease in cNOS activity in colon mucosa. Both COX-2 (celecoxib) and dual COX-2/5-LOX (2A5DHT) inhibitors enhanced cNOS and arginase acting in combination with acute stress. The concentration of L-arginine remained unchanged in most of the groups, but combination of dual COX-2/5-LOX inhibitor and acute stress raised this parameter.