Intracolonic administration of zileuton, a selective 5-lipoxygenase inhibitor, accelerates healing in a rat model of chronic colitis.
BACKGROUND
5-Lipoxygenase products play a part in inflammatory response.


OBJECTIVE
The effect of intracolonic administration of zileuton (a 5-lipoxygenase inhibitor) on colonic damage and eicosanoid local release was assessed in a rat model of colitis.


METHODS
Ninety rats with trinitrobenzenesulphonic acid induced colitis were randomised to receive placebo, 5-aminosalicylic acid (50 mg/kg), or zileuton (50 mg/kg) intracolonically for four weeks. Local eicosanoid release was monitored by intracolonic dialysis throughout the study. The colon was removed for macroscopic and histological assessment at weeks 1, 2, and 4 after colitis induction in 10 rats of each group.


RESULTS
Zileuton significantly reduced macroscopic damage score after four weeks of treatment in comparison with the other two groups (p = 0.034). In addition, zileuton administration significantly increased the intracolonic release of both thromboxane B2 at week 1 (p = 0.05) and prostaglandin E2 at weeks 2 and 4 (p < 0.05). Zileuton and 5-aminosalicylic acid decreased leukotriene B4 release by 90% at day 3.


CONCLUSIONS
Intracolonic zileuton, compared with 5-aminosalicylic acid and placebo, seems to improve the course of the disease in a model of chronic colitis. This effect may be related to an increased and maintained production of prostaglandin E2 together with inhibition of leukotriene B4 synthesis.
Bertrán
X
X
Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
Mañé
J
J
Fernández-Bañares
F
F
Castellá
E
E
Bartolí
R
R
Ojanguren
I
I
Esteve
M
M
Gassull
M A
MA
D000636:Aminosalicylic Acids / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use; D002908:Chronic Disease; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D003106:Colon / Q000187:drug effects / Q000473:pathology*; D015777:Eicosanoids / Q000032:analysis*; D005260:Female; D006918:Hydroxyurea / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016859:Lipoxygenase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use*; D019804:Mesalamine; D011863:Radioimmunoassay; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology
D000636:Aminosalicylic Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015777:Eicosanoids; D016859:Lipoxygenase Inhibitors; D019804:Mesalamine; D014302:Trinitrobenzenesulfonic Acid; C063449:zileuton; D006918:Hydroxyurea