Serum and Tissue Transglutaminase Correlates with the Severity of Inflammation in Induced Colitis in the Rat

Abstract

Simple rat models of acute and chronic colonic inflammation were used to study the behaviour in serum and mucosa of transglutaminase (TG), an enzyme recently found to be reduced in serum of patients with inflammatory bowel disease (IBD) and related to the activity index of the disease. In the first model the intraluminal administration of 400 mM lactic acid in the colon caused an acute inflammation resembling that of florid ulcerative colitis in humans. In the second, intraluminal administration of the hapten 2,4,6-trinitrobenzenesulphonic acid (TNB) (10 or 30 mg) in 0.25 ml of ethanol as a ‘barrier breaker’ produced a chronic inflammatory disease. The results showed a reduced TG activity in colon of rats in both acute and chronic induced colitis (447 ± 75 versus 1344 ± 59 mU/g protein (p < 0.001) and 484 ± 59 versus 1204 ± 75 mU/g protein (p < 0.001)). This decreased activity was related to the severity of mucosal damage, which was dose-dependent. Moreover, in severe colitis the immunohistochemistry showed a TG location in repairing tissue. Serum TG activity was decreased after TNB administration (1.36 ± 0.05 versus 3.44 ± 0.20 mU/ml (p < 0.001)) but not after lactic acid treatment (3.97 ± 0.11 versus 3.78 ± 0.16 mU/ml). In summary, the reduction of TG activity in both tissue and serum when the damage is stabilized reflects the altered morphofunctional integrity of the colon and suggests that serum assay of this enzyme could be a simple marker of intestinal mucosal status in IBD.

Key Words:

• Experimental colitis
• histologic activity
• transglutaminase