Beneficial effects of Batimastat (BB-94), a matrix metalloproteinase inhibitor, in rat experimental colitis

Background and Aims: Matrix metalloproteinases (MMPs) represent a group of enzymes that regulate cell-matrix com position playing a major role in the inflammatory response. In the present study we evaluated the ability of the MMP inhibitor Batimastat (BB-94) to modify the course of experimental coli tis induced in the rat by trinitrobenzensulfonic acid (TNB). Methods: Colit is was induced in 40 rats by intracolonic administration of TNB. Animals we re divided into four groups of ten rats each: group 1 received only intraco lonic TNB, group 2 received TNB+5 mg/kg intraperitoneal BB-94, group 3 TNB10 mg/kg BB-94 and group 4 TNB+20 mg/kg BB-94. The MMP inhibitor was admini stered 30 min before induction of colitis and twice daily until death. Ten rats receiving only intracolonic 0.9% saline served as controls. Animals we re killed after seven days; segments of colon were removed and used for his tological score of inflammation and myeloperoxidase (MPO) activity. Results : Rats receiving only intracolonic 0.9% saline showed no evidence of coliti s. The inflammation score was 0.9, MPO activity 0.235 U/mg. Group 1 (TNB-tr eated rats) exhibited a high inflammation score (12.4) and MPO activity (0. 715 U/mg). Conversely, BE-94-treated rats showed, compared to the TNB group , a significantly lower inflammation score and MPO activity in a dose-depen dent fashion. Group 2: inflammatory score 10.1, MPO activity 0.474 (p < 0.0 5 vs. TNB); group 3: inflammatory score 8.3, MPO activity 0.287 (p < 0.01 v s. TNB); group 4: inflammatory score 5.0, MPO activity 0.256 (p < 0.01 vs. TNB). Conclusions: Treatment with BB-94 has dose-dependent beneficial effec ts on the inflammatory alterations in rat experimental colitis. Thus, the i nhibition of MMPs may represent a novel therapeutic approach for treatment of intestinal inflammation. Copyright (C) 2001 S. Karger AG, Basel.