title: Agmatine induces gastric protection against ischemic injury by reducing vascular permeability in rats.
abstract: OBJECTIVE
  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 μg/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 μg/stomach vs 1.175 ± 0.374 μg/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.
  
  
  CONCLUSIONS
  AGM protects the stomach against I/R injury by reducing vascular permeability and inflammation. This protection is possibly mediated by Akt/PI3K.
authors.affiliation: Department of Physiology, College of Medicine and King Khalid University Hospital, King Saud University, Riyadh 11461, Saudi Arabia.
authors.forename: Abeer A
authors.initials: AA
authors.lastname: Al Masri
authors.forename: Eman
authors.initials: E
authors.lastname: El Eter
mesh_terms: D000376:Agmatine / Q000494:pharmacology*; D000730:Androstadienes / Q000494:pharmacology; D042683:Angiopoietin-1 / Q000378:metabolism; D042702:Angiopoietin-2 / Q000378:metabolism; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D018932:Chemokine CCL2 / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D015536:Down-Regulation; D005753:Gastric Mucosa / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020011:Protective Agents / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013270:Stomach / Q000098:blood supply* / Q000187:drug effects* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D042683:Angiopoietin-1; D042702:Angiopoietin-2; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020011:Protective Agents; D047428:Protein Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D000376:Agmatine; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D000077191:Wortmannin