A protective effect of the synthetic coumarine derivative Cloricromene against DNB-colitis in the rat.
Biologic therapies, namely antibodies against tumor necrosis factor-alpha (TNF- alpha) or its receptors, have been recently introduced for the treatment of patients with inflammatory bowel disease (IBD). In the present study the effects of cloricromene, an agent with known antithrombotic actions and with demonstrated anti-TNF- alpha activity were investigated in a rat model of experimental colitis induced with dinitrobenzenesulphonic acid (DNB)/ethanol. We investigated three experimental groups: (i) sham-colitis with vehicle-treatment (controls, n = 6), (ii) colitis with vehicle-treatment (saline, 0.1 ml s.c., daily) (DNB-V, n = 7), (iii) colitis with cloricromene-treatment (10 mg/kg/day s.c.; DNB-C, n = 8). After 7 days, the weight gain, colon wet weight, macroscopic damage score, coagulation parameters, colon mucosal myeloperoxidase activity (MPO), and tissue concentrations of TNF- alpha and of macrophage inhibitory peptide-2 (MIP-2) were assessed. The macroscopic damage scores, colon wet weights, and tissue MIP-2 levels were significantly increased in untreated and in cloricromene-treated rats compared with controls. Cloricromene treatment was associated with a minor body weight loss (p < 0.025) and significantly reduced tissue concentrations of MPO and TNF-alpha (p < 0.02, both). Blood coagulation parameters were not affected by treatment. In the DNB-model treatment with cloricromene effectively reduces tissue levels of TNF- alpha and of myeloperoxidase, whereas MIP-2 concentrations were not influenced. Blood coagulation parameters remained unchanged indicating safety of treatment. Since biological therapies frequently fail to improve disease course of IBD, other therapies with similar targets should be further investigated.
Fries
Walter
W
Dipartimento di Medicina Interna e Terapia Medica, Università di Messina, Italy. walter.fries@flashnet.it
Mazzon
Emanuela
E
Sturiale
Sergio
S
Giofré
Maria R
MR
Lo Presti
Maria A
MA
Cuzzocrea
Salvatore
S
Campo
Giuseppe M
GM
Caputi
Achille P
AP
Longo
Giuseppe
G
Sturniolo
Giacomo C
GC
D000818:Animals; D001557:Benzenesulfonates; D001835:Body Weight / Q000187:drug effects; D054426:Chemokine CXCL2; D002866:Chromonar / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D007279:Injections, Subcutaneous; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D015846:Monokines / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001557:Benzenesulfonates; D054426:Chemokine CXCL2; D015846:Monokines; D010975:Platelet Aggregation Inhibitors; D014409:Tumor Necrosis Factor-alpha; C007488:dinitrobenzenesulfonic acid; C025945:cloricromen; D009195:Peroxidase; D002866:Chromonar