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Preventive Effect of Zaprinast and 3-Isobutyl, 1-Methylxanthine (Phosphodiesterase Inhibitors) on Gastric Injury Induced by Nonsteroidal Antiinflammatory Drugs in Rats

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Abstract

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.

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Authors and Affiliations

  1. Servicio de Aparato Digestivo, Hospital Universitario Virgen de la Macarena, 41009, Seville, Spain

    Juan M. Herrerías & Juan M. Herrerías Jr.

  2. Servicio Central de Investigación en Ciencias de la Salud, Universidad de Cádiz, 11002, Cádiz, Spain

    José M. Esteban & Pilar Esteban

  3. Departamento de Medicina, Facultad de Medicina, Universidad de Granada, 18071, Granada, Spain

    Antonio M. Caballero-Plasencia & Manuel Valenzuela-Barranco

  4. Departamento de Farmacología, Facultad de Farmacología, Universidad de Sevilla, 41071, Seville, Spain

    Virginia Motilva, Catalina Alarcón & M. José Martín

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  1. Juan M. Herrerías
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Herrerías, J.M., Esteban, J.M., Caballero-Plasencia, A.M. et al. Preventive Effect of Zaprinast and 3-Isobutyl, 1-Methylxanthine (Phosphodiesterase Inhibitors) on Gastric Injury Induced by Nonsteroidal Antiinflammatory Drugs in Rats. Dig Dis Sci 48, 986–991 (2003). https://doi.org/10.1023/A:1023020201005

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