Therapeutic effect of phenantroline in two rat models of inflammatory bowel disease.
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 (PGE2, TXB2 and LTB4) 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 PGE2, TXB2 and LTB4 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.
Medina
C
C
Digestive Disease Research Unit, Hospital Vall d'Hebron, Barcelona, Spain.
Videla
S
S
Radomski
A
A
Radomski
M
M
Antolín
M
M
Guarner
F
F
Vilaseca
J
J
Salas
A
A
Malagelada
J R
JR
D000818:Animals; D002614:Chelating Agents / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D003106:Colon / Q000473:pathology; D016264:Dextran Sulfate; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D010618:Phenanthrolines / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D014302:Trinitrobenzenesulfonic Acid; D015032:Zinc
D002614:Chelating Agents; D010618:Phenanthrolines; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate; D008666:Metalloendopeptidases; D015032:Zinc