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.