Therapeutic Effect of Phenantroline in Two Rat Models of Inflammatory Bowel Disease

Abstract

Background: Phenantroline is a zinc-chelator that inhibits biological activities of matrix metalloproteinases (MMPs). Over-expression of MMPs can accelerate tissue destruction and disrupt subsequent tissue repair. The effects of phenantroline in two rat models of inflammatory bowel disease (IBD) are evaluated: transmural colitis induced by trinitrobenzensulphonic acid (TNBS) and distal colitis caused by dextran sulphate sodium (DSS). Methods: Transmural colitis was induced by TNBS in two groups of 15 rats each, and distal colitis was induced by DSS in two other groups of 15 rats each. Phenantroline was administered by oral gavage at 20 mg kg -1 day -1 to the test groups, whereas matched control groups received oral vehicle. On the last day of dosing, rats were subjected to intracolonic dialysis under anaesthesia for assessment of luminal eicosanoid release (PGE 2 , TXB 2 and LTB 4 ) and euthanized. Colons were removed and lesions were blindly scored according to macroscopic and histological scales. Myeloperoxidase (MPO) activity was measured in homogenates of colonic tissue. Results: In the TNBS model, phenantroline treatment significantly reduced colonic strictures; in the DSS model, phenantroline significantly decreased scores of epithelial injury. In both models, the levels of PGE 2 , TXB 2 and LTB 4 and tissue MPO were not significantly altered. Conclusions: Although phenantroline did not modify the activity of inflammatory mediators, this compound substantially reduced intestinal injury associated with tissue remodelling.

• Dextran Sulphate Sodium Eicosanoids Matrix Metalloproteinases Myeloperoxidase Trinitrobenzensulphonic Acid