Original Article
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World J Gastroenterol. Jul 28, 2013; 19(28): 4464-4474
Published online Jul 28, 2013. doi: 10.3748/wjg.v19.i28.4464
Antioxidant properties of glutamine and its role in VEGF-Akt pathways in portal hypertension gastropathy
Camila Marques, Francielli Licks, Ingrid Zattoni, Beatriz Borges, Luiz Eduardo Rizzo de Souza, Claudio Augusto Marroni, Norma Possa Marroni
Camila Marques, Francielli Licks, Universidade Federal do Rio Grande do Sul-PPG Fisiologia, Porto Alegre 90000100, Brazil
Ingrid Zattoni, Beatriz Borges, Luiz Eduardo Rizzo de Souza, Universidade Federal do Paraná, Curitiba 81531900, Brazil
Claudio Augusto Marroni, Departamento de Medicina, Interna-Gastroenterologia-Universidade, Federal de Ciências da Saúde de Porto Alegre, Porto Alegre 90000100, Brazil
Norma Possa Marroni, Universidade Federal do Rio Grande do Sul-PPG Fisiologia, Universidade Luterana do Brasil, Porto Alegre 90000100, Brazil
Author contributions: Marques C, Licks F, Borges B, Souza LER, Marroni CA and Marroni NP contributed equally to this work; Marroni NP designed the research; Marques C, Licks F, Zattoni I, Borges B and Souza LER performed the research; Marques C wrote the manuscript.
Supported by Hospital de Clínicas de Porto Alegre, FIPE 07284 e 09195, CNPq
Correspondence to: Norma Possa Marroni, PhD, Universidade Federal do Rio Grande do Sul-PPG Fisiologia, Universidade Luterana do Brasil, Porto Alegre 90000100, Brazil. nmarroni@terra.com.br
Telephone: +55-51-99643011 Fax: +55-51-33083453
Received: December 27, 2011
Revised: March 15, 2012
Accepted: April 12, 2012
Published online: July 28, 2013
Abstract

AIM: 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.

CONCLUSION: 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.

Keywords: Partial portal vein ligation; Oxidative stress; Glutamine; Portal hypertension; Rats