Prophylactic potential of montelukast against mild colitis induced by dextran sulphate sodium in rats.
Cysteinyl leukotrienes play a part in inflammatory processes such as inflammatory bowel diseases. The present study aimed to evaluate the effects of the cys-LT-1 receptor antagonist montelukast on a mild colitis model in rats. Colitis was induced by administrating 4% dextran sulphate sodium (DSS, MW 45,000) in drinking water for 9 days. Montelukast (10 mg/kg/day) or vehicle was given by gastric gavage once daily simultaneously with DSS administration. A healthy control group receiving water as drinking fluid and vehicle by gastric gavage was included. Body weight loss, consistency of faeces (loose/diarrhoea) and occult blood in the faeces/ gross bleeding were assessed on days 6 - 9. After sacrifice, the following were assessed: colonic histology, the expression of inducible nitric oxide synthase, macrophage/monocyte marker ED1, cyclooxygenase-1 and cyclooxygenase-2, as well as the production of leukotriene B(4) and E(4), prostaglandin E(2), its metabolite bicyclic-prostaglandin E(2) and thromboxane B(2) in the colonic tissue incubation in vitro. Rats receiving DSS exhibited bloody diarrhoea from day 6 onwards. Montelukast significantly reduced the occult blood in the faeces/ gross bleeding, maintained normal body weight gain and tended to decrease the ratio of leukotriene B(4)/ prostaglandin E(2) production in the colon in vitro. The results indicate that montelukast has some potential to ameliorate mild experimental colitis induced by DSS.
Holma
R
R
Institute of Biomedicine, Pharmacology, University of Helsinki, Finland.
Salmenperä
P
P
Virtanen
I
I
Vapaatalo
H
H
Korpela
R
R
D000085:Acetates / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000284:Administration, Oral; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003521:Cyclopropanes; D016264:Dextran Sulfate / Q000008:administration & dosage / Q000633:toxicity*; D015232:Dinoprostone / Q000378:metabolism; D007120:Immunochemistry; D007074:Immunoglobulin G / Q000378:metabolism; D020024:Leukotriene Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009780:Occult Blood; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D013440:Sulfides; D013929:Thromboxane B2 / Q000378:metabolism
D000085:Acetates; D001643:Bridged Bicyclo Compounds; D003521:Cyclopropanes; D007074:Immunoglobulin G; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D007975:Leukotriene B4; D013929:Thromboxane B2; D016264:Dextran Sulfate; D052247:Nitric Oxide Synthase Type II; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone; C093875:montelukast