Effects of thromboxane synthase inhibition on in vivo release of inflammatory mediators in chronic ulcerative colitis.
OBJECTIVE
To evaluate the effects of a thromboxane inhibitor on the production of eicosanoids by the colonic mucosa of patients with chronic ulcerative colitis.


METHODS
Fourteen patients with active left-sided ulcerative colitis were divided into in two treatment groups. Seven patients received oral ridogrel (300 mg twice daily) and seven 5-aminosalicylic acid (5-ASA; 1 g twice daily) for 4 weeks. Intracolonic eicosanoid and elastase release were measured using a colonic double-lumen perfusion technique. An isotonic solution was infused 50 cm from the anal verge at the rate of 5 ml/min, and recovered by siphonage 30 cm distally. Effluents were assayed for thromboxane B2 (TXB2), prostaglandin E2 (PGE2), and leukotriene B4 (LTB4) by radioimmunoassay (RIA), and for polymorphonuclear elastase by immunoactivation. Clinical and colonoscopic criteria were used to determine activity before and after treatment.


RESULTS
Four of the seven patients in the ridogrel group and five of the seven in the 5-ASA group showed clinical and colonoscopic improvement. Intraluminal elastase release decreased in every responding patient in the 5-ASA group (P < 0.05) and in three out of seven responders in the ridogrel group. Basal eicosanoid release was similar in both groups. In the responders, 5-ASA significantly reduced the release of the three eicosanoids (P < 0.05). Ridogrel reduced the release of TXB2 to 31% of basal levels (P < 0.01) but the release of PGE2 and LTB4 was not affected.


CONCLUSIONS
These results suggest that ridogrel is an oral active selective inhibitor of thromboxane synthetase, which modifies the pattern of colonic eicosanoid generation in patients with chronic ulcerative colitis. Oral ridogrel may be a useful treatment for patients with non-severe ulcerative colitis, although specific indications require further studies.
Casellas
F
F
Digestive System Research Unit, Vall d'Hebron General Hospital, Barcelona, Spain.
Papo
M
M
Guarner
F
F
Antolín
M
M
Segura
R M
RM
Armengol
J R
JR
Malagelada
J R
JR
D000328:Adult; D000368:Aged; D000636:Aminosalicylic Acids / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002908:Chronic Disease; D003093:Colitis, Ulcerative / Q000378:metabolism*; D003106:Colon / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007975:Leukotriene B4 / Q000096:biosynthesis; D008297:Male; D019804:Mesalamine; D008875:Middle Aged; D010196:Pancreatic Elastase / Q000378:metabolism; D010421:Pentanoic Acids / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D013929:Thromboxane B2 / Q000096:biosynthesis*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D000636:Aminosalicylic Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D010421:Pentanoic Acids; D011725:Pyridines; D007975:Leukotriene B4; D019804:Mesalamine; D013929:Thromboxane B2; D010196:Pancreatic Elastase; D013930:Thromboxane-A Synthase; D015232:Dinoprostone; C060219:ridogrel