Beneficial effects of Batimastat (BB-94), a matrix metalloproteinase inhibitor, in rat experimental colitis.
OBJECTIVE
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.
Di Sebastiano
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1st Department of Surgery, Bolzano General Hospital, Bolzano, Italy. diseb@hotmail.com
di Mola
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Artese
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Rossi
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Mascetta
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Pernthaler
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Innocenti
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D000818:Animals; D002908:Chronic Disease; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D006416:Hematoxylin; D007413:Intestinal Mucosa / Q000187:drug effects / Q000293:injuries; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000627:therapeutic use*; D009195:Peroxidase / Q000378:metabolism; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000627:therapeutic use*; D011480:Protease Inhibitors / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013876:Thiophenes / Q000037:antagonists & inhibitors* / Q000627:therapeutic use*; D014302:Trinitrobenzenesulfonic Acid / Q000009:adverse effects
D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D013876:Thiophenes; D010649:Phenylalanine; D014302:Trinitrobenzenesulfonic Acid; C080985:batimastat; D009195:Peroxidase; D020782:Matrix Metalloproteinases; D006416:Hematoxylin