Abstract | BACKGROUND: No published study has addressed the effect of genistein postconditioning on gastric ischemia-reperfusion (GI-R) injury in rats. AIM: METHODS AND RESULTS: Chloraldurat-anesthetized rats underwent occlusion of the celiac artery for 30 min, followed by 60 min of reperfusion. Based on this animal model of gastric ischemia-reperfusion injury, genistein at doses of 100, 500 or 1,000 μg/kg was administered via peripheral vein 5 min before reperfusion. The dose of 500 μg/kg was optimal for postconditioning, at which the severity of I-R-induced gastric injury significantly decreased. Immunohistochemistry also showed that gastric mucosal cell apoptosis decreased. Capsazepine (CPZ), a specific antagonist for the capsaicin receptor, was administered (1,000 μg/kg, i.v.) just before ischemia. Capsaicin (50 mg/kg, s.c.) once a day for 4 days reversed the protective effects of genistein. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting showed increased calcitonin gene-related peptide (CGRP) expression in genistein group but not in capsazepine or capsaicin group. CGRP inhibitor CGRP8-37 also prevented the effects of genistein in decreasing gastric mucosal injury index. In addition, PI3K inhibitor LY294002 (1.5 mg/kg) reversed the protective effect of genistein. Compared with genistein group, Western blots also demonstrated decreased Akt phosphorylation in LY294002 group. CONCLUSION: Our data suggest that capsaicin receptors mediated the protective effects of genistein postconditioning. CGRP secreted by activated capsaicin-sensitive neurons played an important role in the protective effects of genistein. PI3K/Akt pathway was also involved in the protective effects of genistein.
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Authors | Dong-Shu Du, Xiao-Bo Ma, Jian-Fu Zhang, Xiao-Yan Zhou, Yu Li, Yong-Mei Zhang, Wei-Li Qiao |
Journal | Digestive diseases and sciences
(Dig Dis Sci)
Vol. 55
Issue 11
Pg. 3070-7
(Nov 2010)
ISSN: 1573-2568 [Electronic] United States |
PMID | 20198432
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Chromones
- Enzyme Inhibitors
- Morpholines
- Phytoestrogens
- TRPV Cation Channels
- 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
- Genistein
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Topics |
- Animals
- Chromones
(pharmacology)
- Enzyme Inhibitors
(pharmacology)
- Genistein
(administration & dosage, therapeutic use)
- In Situ Nick-End Labeling
- Ischemic Preconditioning
(methods)
- Morpholines
(pharmacology)
- Phytoestrogens
(administration & dosage, therapeutic use)
- Rats
- Rats, Sprague-Dawley
- Reperfusion Injury
(prevention & control)
- TRPV Cation Channels
(physiology)
- Up-Regulation
(physiology)
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