Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Mar 27, 2019; 11(3): 273-286
Published online Mar 27, 2019. doi: 10.4254/wjh.v11.i3.273
Protective action of glutamine in rats with severe acute liver failure
Elizângela G Schemitt, Renata M Hartmann, Josieli R Colares, Francielli Licks, Jéferson O Salvi, Cláudio A Marroni, Norma P Marroni
Elizângela G Schemitt, Renata M Hartmann, Josieli R Colares, Francielli Licks, Jéferson O Salvi, Cláudio A Marroni, Norma P Marroni, Laboratory of Experimental Hepatology and Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre 90040060, Brazil
Elizângela G Schemitt, Renata M Hartmann, Josieli R Colares, Francielli Licks, Jéferson O Salvi, Norma P Marroni, Laboratory of Oxidative Stress and Antioxidants, Universidade Luterana do Brasil, Canoas 92425900, Brazil
Author contributions: Schemitt EG, Hartmann RM, Colares JR and Marroni NP contributed to study conception and design; Schemitt EG, Hartmann RM, Colares JR, Licks F and Salvi JO contributed to data acquisition, data analysis and interpretation, and writing of article; Schemitt EG, Marrini CA and Marroni NP contributed to editing and reviewing of article; all authors have read and approved of the final version of the article.
Supported by: FIPE/Hospital de Clinicas of Porto Alegre.
Institutional review board statement: This study was conducted at the Animal Experimentation Unit and the Laboratory of Experimental Hepatology and Gastroenterology, Hospital de Clínicas of Porto Alegre, after approval from the Institutional Animal Care and Use Committee, No. CEUA 15-0175.
Conflict-of-interest statement: The authors have no conflicts of interest to disclose.
ARRIVE guidelines statement: The authors followed the ARRIVE checklist.
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/
Corresponding author: Claudio A Marroni, PhD, Professor, Laboratory of Experimental Hepatology and Gastroenterology, Hospital de Clínicas de Porto Alegre, Rua José Kanan Aranha 102, Porto Alegre 90040060, Brazil. nmarroni@terra.com.br
Telephone: +55-51-999638306
Received: October 30, 2018
Peer-review started: October 30, 2018
First decision: December 21, 2018
Revised: January 29, 2019
Accepted: March 12, 2019
Article in press: March 12, 2019
Published online: March 27, 2019
Processing time: 148 Days and 18.1 Hours
ARTICLE HIGHLIGHTS
Research background

Severe acute liver failure (SALF) is a serious disease that does not have an effective treatment and liver transplantation is the only viable alternative. The mechanisms intrinsic to the pathophysiology of the disease are still not well understood and therefore, experimental studies are of fundamental importance in the attempt to elucidate the mechanisms and therapeutic agents. Glutamine is an amino acid used in the treatment of various diseases of the gastrointestinal tract and has been shown to be promising in previous studies of liver diseases.

Research motivation

In a previous study, the authors developed the experimental model of thioacetamide-induced SALF across different times. From the obtained data the best model to be studied was defined. It was evaluated the antioxidant action of glutamine that presented promising data. With the continuity of the research, we evaluated in this work the pathways of oxidative stress and inflammatory process at the molecular level, involved in the SALF. The results of this research are important indicators of the restorative role of glutamine in the SALF experimental model and will certainly provide a basis for a better understanding of the evaluated mechanisms contributing to the continuity of the studies.

Research objectives

The objective of this study was to investigate the action of glutamine on parameters of oxidative stress and inflammatory process in the experimental SALF. It is known that such parameters are implicated in the pathophysiology of various diseases. The understanding of the routes studied offers a basis for further studies that may evaluate other pathways involved in the disease, as well as the action of other therapeutic agents.

Research methods

To induce SALF in wistar rats the xenobiotic thioacetamide was used. The animals were randomized into different groups. In the treatment groups, the animals received doses of glutamine intraperitoneally. Blood tests were performed to evaluate hepatic integrity through a commercial kit. Liver portions were used for histopathological evaluation through hematoxylin and eosin staining. Techniques based on spectrophotometry were performed through protocols for the analysis of oxidative stress and inflammatory process. Protein expression was performed by Western Blot and cytokine analysis was done using multiplex technology based on magnetic beads through commercial kit.

Research results

Glutamine reduced hepatic integrity enzymes and restored the liver of the animals evidenced by decreased necrosis, balloonization and inflammation in the histopathological analysis. In addition, glutamine reduced lipid peroxidation and restored antioxidant enzyme activity. It was evidenced the decrease of the expression of proteins of the oxidative system and of the inflammatory process. Glutamine was able to increase the levels of interleukin 10, an important anti-inflammatory cytokine and also the expression of Nrf2, NQO1 and GSH levels, important proteins of the antioxidant protection system.

Research conclusions

When evaluating mechanisms implicated in the experimental SALF, studying parameters of oxidative stress and inflammatory process, it was possible to observe the protective action of glutamine in the liver of the animals. It is possible to confirm with this study that the oxidative stress and the inflammatory process play a primordial role in the progression of the disease, evidenced by the study of the molecular aspects. Glutamine has been shown to be effective by activating the antioxidant system and minimizing damage from the inflammatory process. Therefore, it presents as a viable alternative in the treatment of patients with severe hepatic insufficiency. Still, new studies confirming the efficacy of glutamine are needed so that in the future it may be part of the routine in the medical clinic.

Research perspectives

In this study the efficacy of the experimental model proposed by the authors in a previous study was confirmed. The pathophysiological mechanisms involved in SALF are diverse and complex. For further clarification of these mechanisms, other molecular routes should be investigated in an attempt to elucidate the aspects involved. We present the details of the involvement of the oxidative stress and the inflammatory process in this research and we hope that further studies can provide technical and theoretical data for the development of viable and effective strategies in the treatment of patients with SALF.