Inflammatory mediator changes in cotton-top tamarins (CTT) after SC-41930 anti-colitic therapy.
Use of the CTT model provides insight into the inflammatory mediator contribution in the pathogenesis of idiopathic colitis. To evaluate anti-colitic efficacy, the leukotriene B4 receptor antagonist and anti-inflammatory agent, SC-41930, was administered (10 mg/kg BW by gavage BID) for 8 weeks to CTTs with histologically confirmed persistent and defined active colitis. The inflammatory mediators LTB4, PGE2, TXB2, and PAF were assayed in colonic dialysate that was collected after 1 1/2 h from four CTTs pre-, mid-, and post-treatment, frozen at -70 degrees C, and analyzed by RIA after HPLC purification. LTB4 levels were lower at mid- and post-treatment and had little inter-animal variation post-treatment. PGE2 and PAF levels were elevated during SC-41930 treatment, but there was a trend towards lower thromboxane B2 levels. Reduced LTB4 (PMN degranulation and chemotaxis) and increased PGE2 (mucosal-protective effect) may, in part, explain the observed efficacy of SC-41930 in active tamarin colitis.
Clapp
N
N
Marmoset Research Center, Oak Ridge (MARCOR), Oak Ridge Associated Universities, TN.
Henke
M
M
Hansard
R
R
Carson
R
R
Walsh
R
R
Widomski
D
D
Anglin
C
C
Fretland
D
D
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000378:metabolism*; D001578:Benzopyrans / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D003092:Colitis / Q000188:drug therapy / Q000378:metabolism*; D003106:Colon / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D010972:Platelet Activating Factor / Q000378:metabolism*; D011863:Radioimmunoassay; D012452:Saguinus; D013929:Thromboxane B2 / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001095:Arachidonic Acids; D001578:Benzopyrans; D010972:Platelet Activating Factor; C059950:SC 41930; D007975:Leukotriene B4; D013929:Thromboxane B2; D015232:Dinoprostone