Phosphodiesterase Type 4 Inhibitors Prevent Ischemia-Reperfusion-Induced Gastric Injury in Rats
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- Kyoi Takashi
- Research Laboratories, Nippon Shinyaku Co., Ltd.
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- Kitazawa Satoru
- Research Laboratories, Nippon Shinyaku Co., Ltd.
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- Tajima Koyuki
- Research Laboratories, Nippon Shinyaku Co., Ltd.
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- Zhang Xin
- Research Laboratories, Nippon Shinyaku Co., Ltd.
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- Ukai Yojiro
- Research Laboratories, Nippon Shinyaku Co., Ltd.
書誌事項
- タイトル別名
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- Phosphodiesterase Type IV Inhibitors Prevent Ischemia-Reperfusion-Induced Gastric Injury in Rats
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抄録
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-α (TNF-α) 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-α 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-α levels and MPO activity. It is concluded that the ability of PDE4 inhibitors to inhibit cytokine TNF-α 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.<br>
収録刊行物
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- Journal of Pharmacological Sciences
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Journal of Pharmacological Sciences 95 (3), 321-328, 2004
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390001205177231104
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- NII論文ID
- 10013335124
- 130000074372
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- NII書誌ID
- AA11806667
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- ISSN
- 13478648
- 13478613
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- NDL書誌ID
- 7012067
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- PubMed
- 15272207
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 使用不可