Experimental colitis in mice: effects of olsalazine on eicosanoid production in colonic tissue

Agents Actions. 1992:Spec No:C76-8.

Abstract

In rodents colitis can be induced by adding 2% (w/v) carrageenan (CARR) for 4 weeks or 10% (w/v) dextran sulphate sodium (DSS) for 7 days to their drinking water. These models are suitable to test anti-inflammatory drugs used in inflammatory bowel disease in man. Mice were treated with olsalazine (400 mg/kg body wt) starting 7 days before the DSS or CARR administration. Colonic tissues were incubated with [1-14C]-arachidonic acid and stimulated with A23187 and, thereafter, the pattern of eicosanoids was determined by separation on HPLC. DSS and CARR produced a marked diffuse inflammatory response in the colon and a subsequent 5-fold increase of all eicosanoids after DSS, whereas after CARR only a 2-fold increase of PGs was observed. Olsalazine treatment decreased all cyclooxygenase and lipoxygenase products to baseline levels.

MeSH terms

  • Aminosalicylic Acids / pharmacology*
  • Animals
  • Arachidonic Acid / pharmacology
  • Calcimycin / pharmacology
  • Carrageenan
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / metabolism
  • Colon / drug effects*
  • Colon / metabolism
  • Dextran Sulfate
  • Disease Models, Animal
  • Eicosanoids / biosynthesis*
  • Female
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Mice
  • Mice, Inbred BALB C

Substances

  • Aminosalicylic Acids
  • Eicosanoids
  • Arachidonic Acid
  • Calcimycin
  • Carrageenan
  • Dextran Sulfate
  • olsalazine