Article Text

PDF

Intracolonic administration of zileuton, a selective 5-lipoxygenase inhibitor, accelerates healing in a rat model of chronic colitis.
  1. X Bertrán,
  2. J Mañé,
  3. F Fernández-Bañares,
  4. E Castellá,
  5. R Bartolí,
  6. I Ojanguren,
  7. M Esteve,
  8. M A Gassull
  1. Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.

    Abstract

    BACKGROUND: 5-Lipoxygenase products play a part in inflammatory response. AIMS: 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.

    Statistics from Altmetric.com

    Request permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.