Effect of caffeine on ibuprofen-induced gastric mucosal damage in rats

During investigations on the effect of caffeine on ibuprofen-induced gastri c mucosal lesions in rats, we have found that caffeine (p.o.) inhibits the development of ibuprofen-induced gastric lesions in a dose-dependent manner (ED50 18.4 mg kg(-1)). To investigate this protective effect of caffeine, we have studied the effect of caffeine on HCl-ethanol-induced gastric mucos al lesions with or without indomethacin pretreatment. Caffeine inhibited the development of HCl-ethanol-induced gastric lesions w ith and without indomethacin pretreatment. These results indicate that caff eine did not act as a mild irritant but, on the contrary, had protective ef fects. We measured the gastric mucosal prostaglandin E-2 (PGE(2)) concentra tions and gastric mucosal blood flow, as representative protective factors for gastric mucosa. Caffeine did not affect the gastric mucosal PGE2 concen trations 4 h after administration of ibuprofen. However, topical administra tion of caffeine resulted in an increase in gastric mucosal blood flow, as measured by laser Doppler flowmetry. We investigated the gastric acid secre tion and gastric mucosal myeloperoxidase activity as representative aggress ive factors for gastric mucosa. When caffeine was administered intraduodena lly in pylorus-ligated rats, gastric acid secretion decreased in a dose-dep endent manner, with an ED50 of 44.9 mg kg(-1). Caffeine decreased ibuprofen -induced gastric myeloperoxidase activity in a dose-dependent manner, with an ED50 of 9.1 mg kg(-1) These findings indicate that caffeine, at least in rats, may inhibit the de velopment of acute gastric mucosal injury. The mechanisms underlying the pr otective actions of caffeine are unclear, but may be related in part to an increase in gastric mucosal blood flow and suppression of neutrophil activa tion.