PMID- 22611311 OWN - NLM STAT- MEDLINE DCOM- 20120917 LR - 20211021 IS - 2219-2840 (Electronic) IS - 1007-9327 (Print) IS - 1007-9327 (Linking) VI - 18 IP - 18 DP - 2012 May 14 TI - Agmatine induces gastric protection against ischemic injury by reducing vascular permeability in rats. PG - 2188-96 LID - 10.3748/wjg.v18.i18.2188 [doi] AB - AIM: To investigate the effect of administration of agmatine (AGM) on gastric protection against ischemia reperfusion (I/R) injury. METHODS: Three groups of rats (6/group); sham, gastric I/R injury, and gastric I/R + AGM (100 mg/kg, i.p. given 15 min prior to gastric ischemia) were recruited. Gastric injury was conducted by ligating celiac artery for 30 min and reperfusion for another 30 min. Gastric tissues were histologically studied and immunostained with angiopoietin 1 (Ang-1) and Ang-2. Vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1) were measured in gastric tissue homogenate. To assess whether AKt/phosphatidyl inositol-3-kinase (PI3K) mediated the effect of AGM, an additional group was pretreated with Wortmannin (WM) (inhibitor of Akt/PI3K, 15 mug/kg, i.p.), prior to ischemic injury and AGM treatment, and examined histologically and immunostained. Another set of experiments was run to study vascular permeability of the stomach using Evan's blue dye. RESULTS: AGM markedly reduced Evan's blue dye extravasation (3.58 +/- 0.975 mug/stomach vs 1.175 +/- 0.374 mug/stomach, P < 0.05), VEGF (36.87 +/- 2.71 pg/100 mg protein vs 48.4 +/- 6.53 pg/100 mg protein, P < 0.05) and MCP-1 tissue level (29.5 +/- 7 pg/100 mg protein vs 41.17 +/- 10.4 pg/100 mg protein, P < 0.01). It preserved gastric histology and reduced congestion. Ang-1 and Ang-2 immunostaining were reduced in stomach sections of AGM-treated animals. The administration of WM abolished the protective effects of AGM and extensive hemorrhage and ulcerations were seen. CONCLUSION: AGM protects the stomach against I/R injury by reducing vascular permeability and inflammation. This protection is possibly mediated by Akt/PI3K. FAU - Al Masri, Abeer A AU - Al Masri AA AD - Department of Physiology, College of Medicine and King Khalid University Hospital, King Saud University, Riyadh 11461, Saudi Arabia. FAU - El Eter, Eman AU - El Eter E LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - World J Gastroenterol JT - World journal of gastroenterology JID - 100883448 RN - 0 (Androstadienes) RN - 0 (Angiopoietin-1) RN - 0 (Angiopoietin-2) RN - 0 (Ccl2 protein, rat) RN - 0 (Chemokine CCL2) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (Protective Agents) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (vascular endothelial growth factor A, rat) RN - 70J407ZL5Q (Agmatine) RN - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - XVA4O219QW (Wortmannin) SB - IM MH - Agmatine/*pharmacology MH - Androstadienes/pharmacology MH - Angiopoietin-1/metabolism MH - Angiopoietin-2/metabolism MH - Animals MH - Capillary Permeability/*drug effects MH - Chemokine CCL2/metabolism MH - Cytoprotection MH - Disease Models, Animal MH - Down-Regulation MH - Gastric Mucosa/metabolism MH - Immunohistochemistry MH - Male MH - Phosphatidylinositol 3-Kinase/metabolism MH - Phosphoinositide-3 Kinase Inhibitors MH - Protective Agents/*pharmacology MH - Protein Kinase Inhibitors/pharmacology MH - Proto-Oncogene Proteins c-akt/antagonists & inhibitors/metabolism MH - Rats MH - Rats, Wistar MH - Reperfusion Injury/metabolism/pathology/*prevention & control MH - Stomach/*blood supply/*drug effects/pathology MH - Vascular Endothelial Growth Factor A/metabolism MH - Wortmannin PMC - PMC3351768 OTO - NOTNLM OT - Agmatine OT - Ischemia reperfusion injury OT - Monocyte chemoattractant protein-1 OT - Stomach OT - Vascular endothelial growth factor OT - Vascular permeability OT - Wortmannin EDAT- 2012/05/23 06:00 MHDA- 2012/09/18 06:00 PMCR- 2012/05/14 CRDT- 2012/05/22 06:00 PHST- 2011/11/26 00:00 [received] PHST- 2012/01/04 00:00 [revised] PHST- 2012/03/09 00:00 [accepted] PHST- 2012/05/22 06:00 [entrez] PHST- 2012/05/23 06:00 [pubmed] PHST- 2012/09/18 06:00 [medline] PHST- 2012/05/14 00:00 [pmc-release] AID - 10.3748/wjg.v18.i18.2188 [doi] PST - ppublish SO - World J Gastroenterol. 2012 May 14;18(18):2188-96. doi: 10.3748/wjg.v18.i18.2188.