[Study on the experimental ulcerative colitis (UC) model induced by dextran sulfate sodium (DSS) in rats (3)].
We have already confirmed that symptoms in the experimental UC model in rats induced by ingesting DSS resembled those of human UC. In the present study, to clarify the participation of chemical mediators concerned with the development and etiology of the experimental UC model, we investigated the effects of superoxide dismutase (SOD), 5-aminosalicylic acid (5-ASA), AA-861, an LTB4-receptor antagonist (LTB4-ra), indomethacin (Ind) and OKY-046 on the DSS-induced UC model in rats. The UC model was produced by giving rats drinking water containing 3% DSS, and animals were selected when bloody stool was observed in more than 90% of the animals. After selection, drugs were intrarectally administered once a day, for 7 days, to UC rats that were given drinking water containing 1% DSS. SOD, 5-ASA, AA-861 and LTB4-ra inhibited the formation of erosions in the large intestine. Furthermore, SOD, 5-ASA and LTB4-ra improved the length of the large intestine of rats that had been shortened by ingesting DSS. On the other hand, neither Ind nor OKY-046 improved the shortening and erosion of the large intestine. From these results, it is concluded that the free radical and lipoxygenase metabolites of arachidonic acid may be partially involved in the DSS-induced UC model in rats.
Kimura
I
I
Preclinical Development Laboratories, Nippon Hoechst Marion Roussel Ltd., Shiga, Japan.
Nagahama
S
S
Kawasaki
M
M
Kataoka
M
M
Sato
M
M
D000636:Aminosalicylic Acids / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D003093:Colitis, Ulcerative / Q000139:chemically induced* / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors; D013482:Superoxide Dismutase / Q000494:pharmacology
D000636:Aminosalicylic Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D008689:Methacrylates; D018102:Receptors, Leukotriene B4; D016264:Dextran Sulfate; D013482:Superoxide Dismutase; C034364:ozagrel; D007213:Indomethacin