Phosphodiesterase Type IV Inhibitors Prevent Ischemia-Reperfusion-Induced Gastric Injury in Rats

Abstract

Abstract. The effects of selective inhibitors of phosphodiesterase type IV (PDE4) on ischemiareperfusion-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-a (TNF-a ) 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-a content and MPO activity induced by ischemiareperfusion. 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-a levels and MPO activity. It is concluded that the ability of PDE4 inhibitors to inhibit cytokine TNF-a 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.

Description of a Novel Phosphodiesterase (PDE)-3 Inhibitor Protecting Mice From Ischemic Stroke Independent From Platelet Function

“…27–31 Additionally, PDEs show beneficial effects after ischemia-reperfusion injury in different organs such as the lung, the kidney, the gut, and especially the brain. 4,32–34 These largely consistent findings in CNS disorders of different causes support the principal therapeutic potential of PDE inhibitors in the field of neurology.…”

Gastric submucosal microdialysis in the detection of rat stomach ischemia—a comparison of the3H2O efflux technique with metabolic monitoring

“…These findings were associated with stable plasma thiols. The present study is not the only one questioning the effect of pure IR on the production of marked hemorrhagic lesions (Kyoi et al 2004).…”

Pharmacological mechanisms underlying the anti-ulcer activity of methanol extract and canthin-6-one of Simaba ferruginea A. St-Hil. in animal models

“…Reduction in intrinsic production of PGs in the gastric mucosa and the increase production of pro-inflammatory cytokines (such as IL-8, IL-1␤ and TNF-␣) in the gastric and plasma, the production of ROS, lipid peroxidation and neutrophil infiltration are intimately associated with the gastric mucosal damage induced by NSAIDs (Kyoi et al, 2004;Akhiani, 2005). TNF-␣ seems to be one of the key factors for several forms of mucosal gastric lesions including those associated with NSAIDs (Martin and Wallace, 2006).…”