Agmatine ameliorates acetic acid-induced colitis in rats: involvement of nitrergic system.

AIM: The aim of the present study is to investigate the anti-inflammatory effect of agmatine through the inhibition of iNOS enzyme in acetic acid-induced rat colitis.

METHODS: Acute colitis was induced by administration of 2 mL of diluted acetic acid (4%) solution rectally. Two hours after colitis induction, animals were treated with normal saline, dexamethasone (2 mg/kg), agmatine (2, 5, 10 mg/kg), L-NAME (30 mg/kg), Aminoguanidine (20 mg/kg), agmatine (2 mg/kg) with L-NAME (30 mg/kg) and agmatine (2 mg/kg) with aminoguanidine (20 mg/kg) intraperitoneally and continued for 3 consecutive days. Assessment of macroscopic and microscopic damage was performed. MPO activity was evaluated by biochemical method. Furthermore, the tissue level of TNF-α was determined by ELISA and the expression level of iNOS protein was detected by immunohistochemistry (IHC).

RESULTS: Dexamethasone (2 mg/kg) and agmatine (5, 10 mg/kg) and subeffective doses of agmatine (2 mg/kg) with aminoguanidine (20 mg/kg) improved macroscopic and microscopic damage compared to acetic acid group (p < .001). In addition, these drugs reduced the activity of MPO (p < .001) and the level of TNF-α (p < .001) in colon tissue compared to acetic acid group. Furthermore, they decreased acetic acid-induced expression of iNOS protein in colon tissue (p < .01, p < .001).

CONCLUSION: It is suggested that the anti-inflammatory activity of agmatine on acetic acid-induced rat colitis may involve the inhibition of iNOS enzyme.