Phosphodiesterase type IV inhibitors prevent ischemia-reperfusion-induced gastric injury in rats.
J Pharmacol Sci
; 95(3): 321-8, 2004 Jul.
Article
en En
| MEDLINE
| ID: mdl-15272207
ABSTRACT
The effects of selective inhibitors of phosphodiesterase type IV (PDE4) on ischemia-reperfusion-induced gastric injuries were investigated in rats. Gastric ischemia was induced by applying a small clamp to the celiac artery, and reoxygenation was performed by removal of the clamp. Ischemia-reperfusion produced gastric hemorrhagic injuries and increased the content of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and myeloperoxidase (MPO) activity in gastric mucosa. Rolipram (0.03-0.3 mg/kg, s.c.) and Ro-20-1724 (0.3-3 mg/kg, s.c.) prevented the development of gastric injury in a dose-dependent manner, and it also inhibited the increase in mucosal TNF-alpha content and MPO activity induced by ischemia-reperfusion. The anti-ulcer drug irsogladine (1-10 mg/kg, p.o.), which is known to possess a PDE4 inhibitory action, also inhibited the gastric injury produced by ischemia-reperfusion, as well as the increase in TNF-alpha levels and MPO activity. It is concluded that the ability of PDE4 inhibitors to inhibit cytokine TNF-alpha synthesis and the infiltration of polymorphonuclear leukocytes underlies their gastroprotective effects in ischemia-reperfusion-induced gastric injury. Our experiments suggest that drugs that inhibit PDE4 isoenzyme, such as the anti-ulcer drug irsogladine, may be a useful adjunct therapy for the treatment of the gastric damage that follows ischemia-reperfusion.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Inhibidores de Fosfodiesterasa
/
Úlcera Gástrica
/
Daño por Reperfusión
/
3',5'-AMP Cíclico Fosfodiesterasas
/
Mucosa Gástrica
/
Antiulcerosos
Límite:
Animals
Idioma:
En
Revista:
J Pharmacol Sci
Asunto de la revista:
FARMACOLOGIA
Año:
2004
Tipo del documento:
Article
País de afiliación:
Japón