Protective role of cyclooxygenase inhibitors in the adverse action of passive cigarette smoking on the initiation of experimental colitis in rats

Eur J Pharmacol. 2001 Jan 5;411(1-2):193-203. doi: 10.1016/s0014-2999(00)00914-6.

Abstract

Clinical and experimental findings had indicated that cigarette smoke exposure, and cyclooxygenase-2, are strongly associated with inflammatory bowel disease. The present study aimed to evaluate the role of cyclooxygenase-2 in the pathogenesis of experimental inflammatory bowel disease as well as in the adverse action of cigarette-smoke exposure. Rats were pretreated with different cyclooxygenase-2 inhibitors (indomethacin, nimesulide, or SC-236 (4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide)) along with cigarette-smoke exposure before 2,4,6-trinitrobenzenesulfonic acid-enema. Results indicated that pretreatment with cyclooxygenase-2 inhibitors not only protected against 2,4,6-trinitrobenzenesulfonic acid-induced inflammatory bowel disease, but also attenuated the potentiating effect of cigarette-smoke exposure on colonic damage. Furthermore, the colonic cyclooxygenase-2 protein and mRNA expression was markedly induced by 2,4,6-trinitrobenzenesulfonic acid-enema, and it was potentiated further by cigarette-smoke exposure, while the cyclooxygenase-1 expression was not changed. The present study suggests that the highly induced cyclooxygenase-2 expression not only plays a pathogenic role in 2,4,6-trinitrobenzenesulfonic acid-induced inflammatory bowel disease, but also contributes to the adverse action of cigarette-smoke exposure on this disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Colitis / enzymology
  • Colitis / etiology
  • Colitis / prevention & control*
  • Colon / drug effects
  • Colon / metabolism
  • Colon / pathology
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology*
  • Gene Expression Regulation, Enzymologic / drug effects
  • Indomethacin / pharmacology
  • Inflammation / enzymology
  • Inflammation / prevention & control
  • Inflammatory Bowel Diseases / chemically induced
  • Inflammatory Bowel Diseases / enzymology
  • Inflammatory Bowel Diseases / prevention & control
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Leukotriene B4 / metabolism
  • Male
  • Membrane Proteins
  • Peroxidase / drug effects
  • Peroxidase / metabolism
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Prostaglandins / biosynthesis
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sulfonamides / pharmacology
  • Tobacco Smoke Pollution / adverse effects*
  • Trinitrobenzenesulfonic Acid / administration & dosage

Substances

  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Membrane Proteins
  • Prostaglandins
  • RNA, Messenger
  • Sulfonamides
  • Tobacco Smoke Pollution
  • Leukotriene B4
  • Trinitrobenzenesulfonic Acid
  • Peroxidase
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Ptgs1 protein, rat
  • nimesulide
  • Indomethacin