Experimental colitis in mice: effects of olsalazine on eicosanoid production in colonic tissue.
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.
Zijlstra
F J
FJ
Department of Pharmacology, Erasmus University, Rotterdam, The Netherlands.
Garrelds
I M
IM
van Dijk
A P
AP
Wilson
J H
JH
D000636:Aminosalicylic Acids / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002351:Carrageenan; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D015777:Eicosanoids / Q000096:biosynthesis*; D005260:Female; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C
D000636:Aminosalicylic Acids; D015777:Eicosanoids; D016718:Arachidonic Acid; D000001:Calcimycin; D002351:Carrageenan; D016264:Dextran Sulfate; C032587:olsalazine