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Amelioration of TNBS-induced colon inflammation in rats by phospholipase A₂ inhibitor

¹Department of Biochemistry, Hadassah Medical School, ²Gastroenterology Unit, Hadassah University Hospital, ³Department of Oral Biology, School of Dental Medicine, and ⁴Department of Pharmacology, School of Pharmacy, Hebrew University Faculty of Medicine, Jerusalem, Israel 91120

Submitted 28 October 2002 ; accepted in final form 23 April 2003

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 trinitrobenzenesulfonic acid-induced colitis. Intraperitoneal 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 mediator production by PLA₂ inhibition is a plausible approach to the treatment of colitis and introduces the ExPLIs as a prototype of a novel NSAID for the treatment of intestinal inflammation.

inflammatory bowel disease; colitis; nonsteroidal anti-inflammatory drugs

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