Lisofylline and lysophospholipids ameliorate experimental colitis in rats.
BACKGROUND
Intestinal inflammatory processes initiate a chain reaction in which membrane-bound lipids generate eicosanoids and phospholipids. Bioactive lipid mediators play a pivotal role in the pathogenesis of intestinal inflammation and colonic mucosa from patients with inflammatory bowel disease contains high levels of phospholipids. Therefore, we investigated the effects of lysophosphatidic acid and lysophosphatidylethanolamine, two natural occurring phospholipids and lisofylline, which decreases lipid peroxidation, in an in-vivo model of intestinal inflammation.


METHODS
Colitis was induced by rectal administration of ethanol and trinitrobenzene sulfonic acid in rats. Rats were treated once daily with either lysophosphatidic acid or lysophosphatidylethanolamine rectally or twice daily intraperitoneally with lisofylline following induction of colitis. Rats were sacrificed after 7 days and the effect of lysophosphatidic acid, lysophosphatidylethanolamine, and lisofylline on colonic damage and inflammation were assessed using standardized macroscopical and histological injury scores.


RESULTS
Treatment with lysophosphatidic acid, lysophosphatidylethanolamine, and lisofylline significantly reduced the degree of inflammation and necrosis in the distal colon compared to control rats. In addition, the weight loss was significantly less in the treatment groups compared to controls. Histological studies revealed a significant reduction of epithelial damage and colonic inflammation.


CONCLUSIONS
The administration of anti-inflammatory lysophospholipids and suppression of proinflammatory lipid metabolites by lisofylline may provide new approaches to ameliorate intestinal inflammation.
Sturm
Andreas
A
Department of Medicine, Divisions of Gastroenterology and Hepatology, Charité-Campus Virchow Clinic, Berlin, Germany.
Zeeh
Jörg
J
Sudermann
Thomas
T
Rath
Heiko
H
Gerken
Guido
G
Dignass
Axel U
AU
D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000517:prevention & control*; D000431:Ethanol; D008246:Lysophospholipids / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D010431:Pentoxifylline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014302:Trinitrobenzenesulfonic Acid
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008246:Lysophospholipids; D000431:Ethanol; D014302:Trinitrobenzenesulfonic Acid; C025189:lisofylline; D010431:Pentoxifylline