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

Digestion. 2001;63(4):234-9. doi: 10.1159/000051895.


Background and aims: Matrix metalloproteinases (MMPs) represent a group of enzymes that regulate cell-matrix composition 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 colitis induced in the rat by trinitrobenzensulfonic acid (TNB).

Methods: Colitis was induced in 40 rats by intracolonic administration of TNB. Animals were divided into four groups of ten rats each: group 1 received only intracolonic TNB, group 2 received TNB+5 mg/kg intraperitoneal BB-94, group 3 TNB+10 mg/kg BB-94 and group 4 TNB+20 mg/kg BB-94. The MMP inhibitor was administered 30 min before induction of colitis and twice daily until death. Ten rats receiving only intracolonic 0.9% saline served as controls. Animals were killed after seven days; segments of colon were removed and used for histological score of inflammation and myeloperoxidase (MPO) activity.

Results: Rats receiving only intracolonic 0.9% saline showed no evidence of colitis. The inflammation score was 0.9, MPO activity 0.235 U/mg. Group 1 (TNB-treated rats) exhibited a high inflammation score (12.4) and MPO activity (0.715 U/mg). Conversely, BB-94-treated rats showed, compared to the TNB group, a significantly lower inflammation score and MPO activity in a dose-dependent fashion. Group 2: inflammatory score 10.1, MPO activity 0.474 (p < 0.05 vs. TNB); group 3: inflammatory score 8.3, MPO activity 0.287 (p < 0.01 vs. 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 effects on the inflammatory alterations in rat experimental colitis. Thus, the inhibition of MMPs may represent a novel therapeutic approach for treatment of intestinal inflammation.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Chronic Disease
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / etiology
  • Disease Models, Animal
  • Hematoxylin
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / injuries
  • Male
  • Matrix Metalloproteinase Inhibitors*
  • Matrix Metalloproteinases / therapeutic use*
  • Peroxidase / metabolism
  • Phenylalanine / analogs & derivatives
  • Phenylalanine / antagonists & inhibitors*
  • Phenylalanine / therapeutic use*
  • Protease Inhibitors / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Severity of Illness Index
  • Thiophenes / antagonists & inhibitors*
  • Thiophenes / therapeutic use*
  • Trinitrobenzenesulfonic Acid / adverse effects


  • Matrix Metalloproteinase Inhibitors
  • Protease Inhibitors
  • Thiophenes
  • Phenylalanine
  • Trinitrobenzenesulfonic Acid
  • batimastat
  • Peroxidase
  • Matrix Metalloproteinases
  • Hematoxylin