title: Antioxidant properties of glutamine and its role in VEGF-Akt pathways in portal hypertension gastropathy.
abstract: OBJECTIVE
  To investigate the effects of glutamine on oxidative/nitrosative stress and the vascular endothelial growth factor (VEGF)-Akt-endothelial nitric oxide synthase (eNOS) signaling pathway in an experimental model of portal hypertension induced by partial portal vein ligation (PPVL).
  
  
  METHODS
  Portal hypertension was induced by PPVL. The PPVL model consists of a partial obstruction of the portal vein, performed using a 20 G blunt needle as a guide, which is gently removed after the procedure. PPVL model was performed for 14 d beginning treatment with glutamine on the seventh day. On the fifteenth day, the mesenteric vein pressure was checked and the stomach was removed to test immunoreactivity and oxidative stress markers. We evaluated the expression and the immunoreactivity of proteins involved in the VEGF-Akt-eNOS pathway by Western blotting and immunohistochemical analysis. Oxidative stress was measured by quantification of the cytosolic concentration of thiobarbituric acid reactive substances (TBARS) as well as the levels of total glutathione (GSH), superoxide dismutase (SOD) activity, nitric oxide (NO) production and nitrotyrosine immunoreactivity.
  
  
  RESULTS
  All data are presented as the mean ± SE. The production of TBARS and NO was significantly increased in PPVL animals. A reduction of SOD activity was detected in PPVL + G group. In the immunohistochemical analyses of nitrotyrosine, Akt and eNOS, the PPVL group exhibited significant increases, whereas decreases were observed in the PPVL + G group, but no difference in VEGF was detected between these groups. Western blotting analysis detected increased expression of phosphatidylinositol-3-kinase (PI3K), P-Akt and eNOS in the PPVL group compared with the PPVL + G group, which was not observed for the expression of VEGF when comparing these groups. Glutamine administration markedly alleviated oxidative/nitrosative stress, normalized SOD activity, increased levels of total GSH and blocked NO overproduction as well as the formation of peroxynitrite.
  
  
  CONCLUSIONS
  Glutamine treatment demonstrated to reduce oxidative damage but does not reduce angiogenesis induced by PH in gastric tissue, demonstrating a beneficial role for the PI3K-Akt-eNOS pathway.
authors.affiliation: Universidade Federal do Rio Grande do Sul-PPG Fisiologia, Porto Alegre 90000100, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Marques
authors.forename: Francielli
authors.initials: F
authors.lastname: Licks
authors.forename: Ingrid
authors.initials: I
authors.lastname: Zattoni
authors.forename: Beatriz
authors.initials: B
authors.lastname: Borges
authors.forename: Luiz Eduardo Rizzo
authors.initials: LE
authors.lastname: de Souza
authors.forename: Claudio Augusto
authors.initials: CA
authors.lastname: Marroni
authors.forename: Norma Possa
authors.initials: NP
authors.lastname: Marroni
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004195:Disease Models, Animal; D004932:Esophageal and Gastric Varices / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology / Q000473:pathology; D005973:Glutamine / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006975:Hypertension, Portal / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008297:Male; D009389:Neovascularization, Pathologic; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D013270:Stomach / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D017392:Thiobarbituric Acid Reactive Substances; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D005973:Glutamine; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D013482:Superoxide Dismutase; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D005978:Glutathione
keywords: Glutamine; Oxidative stress; Partial portal vein ligation; Portal hypertension; Rats
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