Randomized Controlled Trial
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World J Gastroenterol. Aug 28, 2014; 20(32): 11406-11414
Published online Aug 28, 2014. doi: 10.3748/wjg.v20.i32.11406
Glutamine prevents oxidative stress in a model of mesenteric ischemia and reperfusion
Gilmara Pandolfo Zabot, Gustavo Franco Carvalhal, Norma Possa Marroni, 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, 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, analyzed the data and wrote the paper; Carvalhal GF analyzed the data and wrote the paper; Marroni NP designed the research; Hartmann RM performed the research; da Silva VD analyzed the pathological data; all authors read an approved the final manuscript.
Supported by Grant from Pro-bolsas/PUCRS
Correspondence to: Gilmara Pandolfo Zabot, Ms Sci, Department of Surgery, School of Medicine, Pontifical Catholic University of Rio Grande do Sul, Rua Duque de Caxias, 1012/19, Marechal Rondon, Porto Alegre, RS 90610-000, Brazil. gilmarapandolfo@terra.com.br
Telephone: +55-51-99357780 Fax: +55-51-30317723
Received: January 17, 2014
Revised: March 14, 2014
Accepted: April 30, 2014
Published online: August 28, 2014
Abstract

AIM: To evaluate preventative effects of glutamine in an animal model of gut ischemia/reperfusion (I/R).

METHODS: Male Wistar rats were housed in a controlled environment and allowed access to food and water ad libitum. Twenty male Wistar rats were divided into four experimental groups: (1) control group (control) - rats underwent exploratory laparotomy; (2) control + glutamine group (control-GLU) - rats were subjected to laparotomy and treated intraperitoneally with glutamine 24 and 48 h prior to surgery; (3) I/R group - rats were subjected to occlusion of the superior mesenteric artery for 30 min followed by 15 min of reperfusion; and (4) ischemia/reperfusion + glutamine group (G + I/R) - rats were treated intraperitoneally with glutamine 24 and 48 h before I/R. Local and systemic injuries were determined by evaluating intestinal and lung segments for oxidative stress using lipid peroxidation and the activity of superoxide dismutase (SOD), interleukin-6 (IL-6) and nuclear factor kappa beta (NF-κB) after mesenteric I/R.

RESULTS: Lipid peroxidation of the membrane was increased in the animals subjected to I/R (P < 0.05). However, the group that received glutamine 24 and 48 h before the I/R procedure showed levels of lipid peroxidation similar to the control groups (P < 0.05). The activity of the antioxidant enzyme SOD was decreased in the gut of animals subjected to I/R when compared with the control group of animals not subjected to I/R (P < 0.05). However, the group that received glutamine 24 and 48 h before I/R showed similar SOD activity to both control groups not subjected to I/R (P < 0.05). The mean area of NF-κB staining for each of the control groups was similar. The I/R group showed the largest area of staining for NF-κB. The G + I/R group had the second highest amount of staining, but the mean value was much lower than that of the I/R group (P < 0.05). For IL-6, control and control-GLU groups showed similar areas of staining. The I/R group contained the largest area of IL-6 staining, followed by the G + I/R animals; however, this area was significantly lower than that of the group that underwent I/R without glutamine (P < 0.05).

CONCLUSION: These results demonstrate that pretreatment with glutamine prevents mucosal injury and improves gut and lung recovery after I/R injury in rats.

Keywords: Ischemia-reperfusion, Glutamine, Lipid peroxidation, Superoxide dismutase, Nuclear factor-kappa beta, Interleukin 6

Core tip: Ischemia-reperfusion (I/R) leads to oxidative stress, with local and systemic consequences. Many enzymes and interleukins have been implicated in this process, among them interleukin-6 (IL-6) and nuclear factor kappa beta (NF-κB). The exact role of these enzymes is still not clear. Some substances, such as glutamine, have been studied as protective agents against oxidative stress. In an animal experimental model of intestinal I/R we have found that glutamine reduced lipid peroxidation, preserved superoxide dismutase activity, and decreased the expression of IL-6 and NF-κB in both lung and intestine, suggesting a protective role of this amino acid in the setting of intestinal I/R.