Effect of Caffeine on Ibuprofen-induced Gastric Mucosal Damage in Rats

• Published in: Journal of pharmacy and pharmacology 1999-07, Vol.51 (7), p.817-824
• Main Authors: Koyama, Rika, Kataoka, Hirofumi, Tanaka, Yoshiyuki, Nakatsugi, Seiichi, Furukawa, Masumi
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Biological and medical sciences; Caffeine - pharmacology; Central Nervous System Depressants - adverse effects; Central Nervous System Stimulants - pharmacology; Dinoprostone - metabolism; Dose-Response Relationship, Drug; Drug toxicity and drugs side effects treatment; Ethanol - adverse effects; Gastric Mucosa - blood supply; Gastric Mucosa - drug effects; Gastric Mucosa - metabolism; Gastric Mucosa - pathology; Gastrointestinal Motility - drug effects; Hydrochloric Acid - adverse effects; Ibuprofen - adverse effects; Male; Medical sciences; Peroxidase - drug effects; Peroxidase - metabolism; Pharmacology. Drug treatments; Rats; Rats, Inbred Strains; Regional Blood Flow - drug effects; Stomach - drug effects; Stomach - pathology; Stomach Diseases - chemically induced; Stomach Diseases - prevention & control; Time Factors; Toxicity: digestive system
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1211/0022357991773014

During investigations on the effect of caffeine on ibuprofen‐induced gastric 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 18.4mg kg−1). To investigate this protective effect of caffeine, we have studied the effect of caffeine on HCl‐ethanol‐induced gastric mucosal lesions with or without indomethacin pretreatment. Caffeine inhibited the development of HCl‐ethanol‐induced gastric lesions with and without indomethacin pretreatment. These results indicate that caffeine did not act as a mild irritant but, on the contrary, had protective effects. We measured the gastric mucosal prostaglandin E2 (PGE2) concentrations and gastric mucosal blood flow, as representative protective factors for gastric mucosa. Caffeine did not affect the gastric mucosal PGE2 concentrations 4 h after administration of ibuprofen. However, topical administration of caffeine resulted in an increase in gastric mucosal blood flow, as measured by laser Doppler flowmetry. We investigated the gastric acid secretion and gastric mucosal myeloperoxidase activity as representative aggressive factors for gastric mucosa. When caffeine was administered intraduodenally in pylorus‐ligated rats, gastric acid secretion decreased in a dose‐dependent manner, with an ED50 of 44.9mg kg−1. Caffeine decreased ibuprofen‐induced gastric myeloperoxidase activity in a dose‐dependent manner, with an ED50 of 9.1mg kg−1. These findings indicate that caffeine, at least in rats, may inhibit the development of acute gastric mucosal injury. The mechanisms underlying the protective actions of caffeine are unclear, but may be related in part to an increase in gastric mucosal blood flow and suppression of neutrophil activation.