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

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-alpha, 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-alpha 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-alpha, 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.