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1 Department of Biochemistry, Hadassah Medical School, Jerusalem, Israel
2 Gastroenterology Unit, Hadassah University Hospital, Jerusalem, Israel
3 Department of Oral Biology, Hebrew University, School of Dental Medicine, Jerusalem, Israel
4 Department of Pharmacology, Hebrew University, School of Pharmacy, Jerusalem, Israel
* To whom correspondence should be addressed. E-mail: yedgar{at}md2.huji.ac.il.
The pathophysiology of inflammatory bowel disease (IBD) involves the production of diverse lipid mediators, namely eicosanoids, lysophospholipids, and platelet activating factor, in which phospholipase A2 (PLA2) is the key enzyme. Accordingly, it has been postulated that control of lipid mediator production by inhibition of PLA2, would be useful for the treatment of IBD. This hypothesis was tested in the present study, by examining the therapeutic effect of a novel extracellular PLA2 inhibitor (ExPLI), composed of carboxymethylcellulose-linked phosphatidylethanolamine (CMPE), on trinitrobenzene-sulfonic acid (TNBS)-induced colitis. I.P. administration of CMPE suppressed the colitis, as measured by mortality rate, intestinal permeability, plasma PLA2 activity, intestinal myeloperoxidase activity and histological morphometry. Current therapeutic approaches for inflammatory conditions focus on the selective control of a lipid mediator(s) (e.g., prostaglandins or leukotrienes). The present study supports the concept that inclusive control of lipid mediators production by PLA2 inhibition is a plausible approach in the treatment of colitis, and introduces the ExPLIs as a prototype of novel NSAID for the treatment of intestinal inflammation.
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