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Differential role of platelet-activating factor in gastric mucosal ulcer healing

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Platelet-activating factor (PAF) is a potent phospholipid-derived messenger involved in a number of diverse pathological conditions, including mediation of inflammatory cascades associated with wound healing. In this study, we investigated the effect of a specific PAF antagonist, BN52020, on the course of experimentally induced gastric mucosal ulcer healing by analyzing apoptotic processes and the mucosal expression of TNF-α, COX-2, and the activity of inducible nitric oxide synthase (NOS-2). Groups of rats were intragstrically pretreated with BN52020 either 24 and 4 h before acetic acid injury (prophylactic) or 24 and 44 h after the injury (therapeutic) and their mucosal tissue subjected to assessment of ulcer healing rate and biochemical measurements. Compared with the controls, the prophylactic administration of BN52020 produced dose-dependent acceleration in ulcer healing, accompanied by an increase in COX-2 expression and a marked reduction in the extent of mucosal apoptosis, TNF-α and NOS-2 activity. A delay in ulcer healing, however, occurred with BN52020 administered therapeutically, and this effect of the agent was reflected in a decreased COX-2 protein expression and a significant increase in the rate of epithelial cell apoptosis, TNF-α, and the mucosal NOS-2 activity. Thus, PAF antagonist, BN52020, when administered prophylactically exerts anti-inflammatory effects that accelerate gastric ulcer healing, while given therapeutically interferes with COX-2 enzyme expression that leads to a protracted inflammatory responses that delay ulcer healing.

Affiliations: 1: Research Center, Room C 875, University of Medicine and Dentistry of New Jersey, NJ Dental School, 110 Bergen Street, P.O. Box 1709, Newark, NJ 07103-2400, USA. Email: slomianybr@umdnj.edu

10.1163/156856003322315587
/content/journals/10.1163/156856003322315587
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/content/journals/10.1163/156856003322315587
2003-09-01
2016-12-05

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