Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 7, 2017; 23(25): 4529-4537
Published online Jul 7, 2017. doi: 10.3748/wjg.v23.i25.4529
Glutamine prevents oxidative stress in a model of portal hypertension
Gilmara Pandolfo Zabot, Gustavo Franco Carvalhal, Norma Possa Marroni, Francielli Licks, Renata Minuzzo Hartmann, Vinícius Duval da Silva, Henrique Sarubbi Fillmann
Gilmara Pandolfo Zabot, Gustavo Franco Carvalhal, Henrique Sarubbi Fillmann, Department of Surgery, School of Medicine, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil
Norma Possa Marroni, Francielli Licks, Renata Minuzzo Hartmann, Department of Gastroenterology, School of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS 90035-903, Brazil
Vinícius Duval da Silva, Department of Pathology, School of Medicine, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil
Author contributions: Zabot GP and Fillmann HS designed and performed the research, analysed the data and wrote the paper; Carvalhal GF analysed the data and wrote the paper; Marroni NP designed the research; Licks F and Hartmann RM performed the research; da Silva VD analysed the pathological data; all authors read and approved the final manuscript.
Institutional review board statement: The study was reviewed and approved by the School of Medicine, Pontifical Catholic University of Rio Grande do Sul.
Institutional animal care and use committee statement: Animal care was in compliance with the normative resolution 04/97 of the Research and Ethics Committee of the Health Research Group and Graduate Teaching Hospital of Porto Alegre.
Conflict-of-interest statement: There are no conflicts of interest.
Data sharing statement: The authors declare that they compared all data from the study.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Gilmara Pandolfo Zabot, Ms, Sci, Department of Surgery, School of Medicine, Pontifical Catholic University of Rio Grande do Sul; Duque de Caxias Street, 1012/19, Porto Alegre, RS 90610-000, Brazil. gilmarapandolfo@terra.com.br
Telephone: +55-51-999357780 Fax: +55-51-34787000
Received: February 2, 2017
Peer-review started: February 9, 2017
First decision: February 23, 2017
Revised: March 3, 2017
Accepted: June 12, 2017
Article in press: June 12, 2017
Published online: July 7, 2017
Processing time: 154 Days and 13.1 Hours
Abstract
AIM

To evaluate the protective effects of glutamine in a model of portal hypertension (PH) induced by partial portal vein ligation (PPVL).

METHODS

Male Wistar rats were housed in a controlled environment and were allowed access to food and water ad libitum. Twenty-four male Wistar rats were divided into four experimental groups: (1) control group (SO) - rats underwent exploratory laparotomy; (2) control + glutamine group (SO + G) - rats were subjected to laparotomy and were treated intraperitoneally with glutamine; (3) portal hypertension group (PPVL) - rats were subjected to PPVL; and (4) PPVL + glutamine group (PPVL + G) - rats were treated intraperitoneally with glutamine for seven days. Local injuries were determined by evaluating intestinal segments for oxidative stress using lipid peroxidation and the activities of glutathione peroxidase (GPx), endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) after PPVL.

RESULTS

Lipid peroxidation of the membrane was increased in the animals subjected to PH (P < 0.01). However, the group that received glutamine for seven days after the PPVL procedure showed levels of lipid peroxidation similar to those of the control groups (P > 0.05). The activity of the antioxidant enzyme GTx was decreased in the gut of animals subjected to PH compared with that in the control group of animals not subjected to PH (P < 0.01). However, the group that received glutamine for seven days after the PPVL showed similar GTx activity to both the control groups not subjected to PH (P > 0.05). At least 10 random, non-overlapping images of each histological slide with 200 × magnification (44 pixel = 1 μm) were captured. The sum means of all areas, of each group were calculated. The mean areas of eNOS staining for both of the control groups were similar. The PPVL group showed the largest area of staining for eNOS. The PPVL + G group had the second highest amount of staining, but the mean value was much lower than that of the PPVL group (P < 0.01). For iNOS, the control (SO) and control + G (SO + G) groups showed similar areas of staining. The PPVL group contained the largest area of iNOS staining, followed by the PPVL + G group; however, this area was significantly smaller than that of the group that underwent PH without glutamine (P < 0.01).

CONCLUSION

Treatment with glutamine prevents gut mucosal injury after PH in rats.

Keywords: Portal hypertension; Endothelial nitric oxide synthase; Glutamine; Glutathione peroxidase; Inducible nitric oxide synthase; Lipid peroxidation

Core tip: Portal hypertension (PH) is characterized by an increased portal pressure gradient. The progressive increase in portal pressure leads to the formation of portosystemic shunts and intestinal hypoxia. Many enzymes have been implicated in this process, among them endothelial nitric oxide synthase and inducible nitric oxide synthase. Some substances, such as glutamine, have been studied as protective agents against oxidative stress. In an experimental model of PH induced by partial portal vein ligation, we have found that glutamine reduced lipid peroxidation and preserved intestinal glutathione peroxidase activity, suggesting a protective role of this amino acid in the setting of PH.