comparative study of the effect of peroxisome proliferator - activated receptor gamma [PPAR - gamma] ligands and angiotensin converting enzyme [ACE] inhibitors on experimental colitis in rats

ABSTRACT

Peroxisome proliferator - activated receplor-gamma [PPAR- gamma], a member of the nuclear hormone receptor superfamily originally shown to play a critical role in adipocyte differentiation and glucose homeostasis, has recently been implicated as a regulator of cellular proliferation and inflammatory responses. In addition, increasing evidence supports an association between inflammation and angiotensin converting enzyme [ACE]. The aim of this study was to investigate the efficacy of ACE inhibitors [captopril and enalapril] and a PPAR- gamma ligand [rosiglitazone] on acetic acid-induced colitis in rats. Colitis was induced by intracolonic injection of 2 ml of 3% acetic acid. One hundred adult male albino rats were studied in this work. The animals were divided into two main groups, each of fifty rats group I, of long duration of inflammation and treatment [Three weeks] and group II, of short duration of inflammation and treatment [two days]. Each group was subdivided into five subgroups, each of ten rats namely; control, acetic acid untreated, captopril, enalapril and rosiglitazone-treated rats. The investigated drugs were given two days after induction of colitis and continued daily for three weeks in group I, and for two days before and two days after induction of colitis in group II. Intracolonic injection of acetic acid in rats produced significant inflammation, assessed by the ulcer index score, weight of the colon and the colonic tissue level of myeloperoxidase enzyme in acetic acid untreated rats of both groups. These parameters were significantly improved by administration of captopril, enalapril and rosiglitazone. The effect of rosiglitazone was more potent than captopril and enalapril in both groups. Furthermore, the colonic tissue level of glutathione reductase enzyme was significantly reduced in acetic acid untreated rats of both groups. This reduction was significantly inhibited by the three investigated drugs in both groups, with better results with rosiglitazone than captopril and enalapril - treated rats in both groups. Rosiglitazone, captopril and enalapril also significantly improved the tissue level of lipid peroxides which was significantly elevated in acetic acid - untreated rats of both groups. However, the efficacy of rosiglitazone in reducing the lipid peroxides level was more significant than captopril and enalapril in both groups. this study provides an evidence that the PPAR- gamma ligand, rosiglitazone and the two ACE inhibitors, captopril and enalapril confer a good anti-inflammatory activity against acetic acid-induced colitis in rats. This leads to improvement of oxidative stress induced by the inflammatory insult, with the better results being with rosiglitazone than with captopril and enalapril