Rolipram, a specific type IV phosphodiesterase inhibitor, ameliorates indomethacin-induced gastric mucosal injury in rats.

Inhibition of type IV phosphodiesterase activity is beneficial in various inflammation mediated by its function to suppress the production of inflammatory cytokines in inflammatory cells. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin are well known to develop gastric mucosal lesion. As pathogenesis of indomethacin induced gastric mucosal lesion, activation of neutrophils and inflammatory cytokine production play critical roles. However, the effect of phosphodiesterase inhibitors on development of gastric mucosal lesion has not been reported. In the present study, we examined the effect of specific type IV phosphodiesterase inhibitor (rolipram) on NSAIDs-induced gastric mucosal lesion. Also, we examined the effect of rolipram on tissue prostaglandin E2 (PGE2) production. Indomethacin-induced gastric mucosal injury was produced by the intragastric administration of indomethacin (30 mg/kg). Rolipram was injected to the rats intraperitoneally 30 min before the indomethacin administration. Ulcer index and tissue myeloperoxidase (MPO) activity of the gastric mucosa was evaluated. The gastric concentration of PGE2 was determined by RIA. Gastric mucosal lesion induced by indomethacin was significantly inhibited with treatment of rolipram. Mucosal MPO activity was also suppressed by administration of rolipram. Gastric mucosal PGE2 concentration was not affected by intraperitoneal injection of rolipram. Based on these data, the beneficial effects of rolipram on indomethacin-induced gastric mucosal injury may be attributed to its anti-inflammatory properties.