Preventive effect of zaprinast and 3-isobutyl, 1-methylxanthine (phosphodiesterase inhibitors) on gastric injury induced by nonsteroidal antiinflammatory drugs in rats.
Cyclic GMP plays an important role in maintaining homeostasis in the gastric mucosa. NSAIDs damage the mucosa by mechanisms that may be mediated by alterations in the intragastric concentration of cyclic GMP. To test this hypothesis we studied the effects of the oral administration of acetylsalicylic acid (100, 300, and 500 mg/kg), piroxicam (5, 10, and 20 mg/kg) and sodium diclofenac (10, 25, 50, and 100 mg/kg), and of their interaction with zaprinast (5 mg/kg) and IBMX (10 mg/kg), on intragastric concentrations of cyclic GMP and the gastric erosive index in rats. All determinations were done 3 hr after the NSAID was given. All NSAIDs induced dose-dependent decreases in mucosal concentrations of cyclic GMP, which correlated inversely with the surface area showing mucosal injury. In contrast, cyclic GMP concentrations remained normal, and no intragastric damage was seen in rats given zaprinast (cyclic GMP-specific phosphodiesterase inhibitor) or IBMX (non-specific phosphodiesterase inhibitor) or in combination with NSAIDs. These findings are in line with the hypothesis that cyclic GMP is involved in the biochemical mechanisms of NSAID-induced gastric injury.
Herrerías
Juan M
JM
Servicio de Aparato Digestivo, Hospital Universitario Virgen de la Macarena, 41009 Seville, Spain.
Esteban
José M
JM
Caballero-Plasencia
Antonio M
AM
Valenzuela-Barranco
Manuel
M
Motilva
Virginia
V
Alarcón
Catalina
C
Martín
José
J
Herrerías
Juan M
JM
Esteban
Pilar
P
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D006152:Cyclic GMP / Q000032:analysis*; D004195:Disease Models, Animal; D004347:Drug Interactions; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology*; D005756:Gastritis / Q000473:pathology; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011322:Primary Prevention; D011688:Purinones / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010726:Phosphodiesterase Inhibitors; D011688:Purinones; C011145:zaprinast; D006152:Cyclic GMP; D015056:1-Methyl-3-isobutylxanthine