Beneficial effect of a novel non-steroidal anti-inflammatory agent with basic character and antioxidant properties on experimental colitis in rats

Ulcerative colitis is a chronic disorder of unknown etiology. Conservative treatment remains empirical, even today. The aim of this study was to test the efficacy of a novel non-steroidal anti-inflammatory agent{5-(2-hydroxy-ethylamino)-1-cyclohexyl-2-pentanone} (compound A), with basic character and antioxidant properties on an experimental model of ulcerative colitis in rats. The effect of this compound was compared with that of methylprednisolone on the histological abnormalities and serum levels of tumor necrosis factor-alpha (TNF-alpha) in experimental colitis produced by 2,4,6-trinitrobenzenesulfonic acid (TNB). A total number of 24 rats were randomly assigned to one of four groups of six rats each, Group 1: colitis without treatment (disease control), group 2: normal animals (control), group 3: induction of experimental colitis treated with methylprednisolone (5.3 x 10(-3) mmol/kg i.v. every day for 7 days) and group 4: induction of experimental colitis plus administration of compound A (0.6 mmol/kg i.v. every day for 7 days). The administration of compound A resulted in a statistically significant reduction of the extent of tissue damage and of certain histological features (edema, inflammatory infiltration) (P<0.05). Compound A also resulted in a statistically significant reduction of the levels of serum TNF-alpha, compared to those of controls (P<0.005). The beneficial effect of this compound was probably due to the combination, on a single molecule, of anti-inflammatory and antioxidant properties as well as to its basic character. The reduction of the serum TNF-alpha levels could be one of the possible mechanism(s) of action of the compound. Further studies are necessary to establish the direct mechanism of action(s) of the drug and to evaluate its long-term efficacy and safety. (C) 2002 Elsevier Science B.V. All rights reserved.