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The protective effect of capsaicin receptor-mediated genistein postconditioning on gastric ischemia-reperfusion injury in rats.

AbstractBACKGROUND:
No published study has addressed the effect of genistein postconditioning on gastric ischemia-reperfusion (GI-R) injury in rats.
AIM:
To examine whether capsaicin receptor-mediated genistein postconditioning protects against gastric ischemia-reperfusion injury via the PI3K/Akt signal pathway.
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.
AuthorsDong-Shu Du, Xiao-Bo Ma, Jian-Fu Zhang, Xiao-Yan Zhou, Yu Li, Yong-Mei Zhang, Wei-Li Qiao
JournalDigestive diseases and sciences (Dig Dis Sci) Vol. 55 Issue 11 Pg. 3070-7 (Nov 2010) ISSN: 1573-2568 [Electronic] United States
PMID20198432 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Chromones
  • Enzyme Inhibitors
  • Morpholines
  • Phytoestrogens
  • TRPV Cation Channels
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Genistein
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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