Acute effects of the cys-leukotriene-1 receptor antagonist, montelukast, on experimental colitis in rats.
Cysteinyl leukotrienes play a part in inflammatory reactions such as inflammatory bowel diseases. The aim of the present study was to evaluate the acute effects of a cys-leukotriene-1 receptor antagonist, montelukast, on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. Montelukast (5, 10 or 20 mg kg(-1) day(-1)), a 5-lipoxygenase inhibitor, zileuton (50 or 100 mg kg(-1) day(-1), a positive control), or the vehicle was administered intracolonically to the rats twice daily throughout the study, starting 12 h before the induction of colitis with TNBS. The severity of colitis (macroscopic and histological assessment, as well as myeloperoxidase activity), the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2, and eicosanoid production in colonic tissue incubation were assessed 24 and 72 h after colitis induction. Montelukast increased prostaglandin E(2) production at 24 h and tended to reduce the cyclooxygenase-2 protein expression at 72 h, but did not influence the severity of colitis. Zileuton failed to decrease the inflammatory reaction in spite of reduced leukotriene B(4) production at 72 h. The results suggest that drugs that block cysteinyl leukotriene receptors have limited potential to ameliorate acute TNBS-induced colitis, but that they exert some beneficial effects which make them capable of modulating the course of colitis.
Holma
R
R
Institute of Biomedicine, Pharmacology, Biomedicum Helsinki, P.O. Box 63, FIN-00014 University of Helsinki, Helsinki, Finland.
Salmenperä
P
P
Riutta
A
A
Virtanen
I
I
Korpela
R
R
Vapaatalo
H
H
D000085:Acetates / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D003092:Colitis / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2; D003521:Cyclopropanes; D007527:Isoenzymes / Q000378:metabolism; D020024:Leukotriene Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D018077:Receptors, Leukotriene; D012720:Severity of Illness Index; D013440:Sulfides
D000085:Acetates; D003521:Cyclopropanes; D007527:Isoenzymes; D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D011804:Quinolines; D018077:Receptors, Leukotriene; D013440:Sulfides; D007975:Leukotriene B4; C412375:cysteinyl leukotriene receptor 2; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C083169:leukotriene D4 receptor; C093875:montelukast