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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Dec 18, 2015; 7(29): 2880-2889
Published online Dec 18, 2015. doi: 10.4254/wjh.v7.i29.2880
Oxidative stress modulation in hepatitis C virus infected cells
Sonia A Lozano-Sepulveda, Owen L Bryan-Marrugo, Carlos Cordova-Fletes, Maria C Gutierrez-Ruiz, Ana M Rivas-Estilla
Sonia A Lozano-Sepulveda, Owen L Bryan-Marrugo, Carlos Cordova-Fletes, Ana M Rivas-Estilla, Department of Biochemistry and Molecular Medicine, School of Medicine, Universidad Autonoma de Nuevo Leon, Monterrey, Nuevo Leon 64460, Mexico
Maria C Gutierrez-Ruiz, Department of Health Sciences, Biological Sciences and Health Division, School of Biological Sciences, Universidad Autonoma Metropolitana, Distrito Federal 09340, Mexico
Author contributions: All the authors contributed to the preparation of this manuscript.
Supported by The CONACYT, No. CB-2011-1-58781 to Ana M Rivas-Estilla (partially); and Red CA Fisiopatología de Enfermedades Hepáticas 2015.
Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors contributed their efforts in this manuscript.
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:
Correspondence to: Ana M Rivas-Estilla, PhD, Department of Biochemistry and Molecular Medicine, School of Medicine, Universidad Autonoma de Nuevo Leon, Av. Francisco I. Madero and Eduardo Aguirre Pequeño, Mitras Centro, Monterrey, Nuevo Leon 64460, Mexico.
Telephone: +52-81-83294174 Fax: +52-81-83337747
Received: April 29, 2015
Peer-review started: May 8, 2015
First decision: September 8, 2015
Revised: November 7, 2015
Accepted: December 1, 2015
Article in press: December 2, 2015
Published online: December 18, 2015

Hepatitis C virus (HCV) replication is associated with the endoplasmic reticulum, where the virus can induce cellular stress. Oxidative cell damage plays an important role in HCV physiopathology. Oxidative stress is triggered when the concentration of oxygen species in the extracellular or intracellular environment exceeds antioxidant defenses. Cells are protected and modulate oxidative stress through the interplay of intracellular antioxidant agents, mainly glutathione system (GSH) and thioredoxin; and antioxidant enzyme systems such as superoxide dismutase, catalase, GSH peroxidase, and heme oxygenase-1. Also, the use of natural and synthetic antioxidants (vitamin C and E, N-acetylcysteine, glycyrrhizin, polyenylphosphatidyl choline, mitoquinone, quercetin, S-adenosylmethionine and silymarin) has already shown promising results as co-adjuvants in HCV therapy. Despite all the available information, it is not known how different agents with antiviral activity can interfere with the modulation of the cell redox state induced by HCV and decrease viral replication. This review describes an evidence-based consensus on molecular mechanisms involved in HCV replication and their relationship with cell damage induced by oxidative stress generated by the virus itself and cell antiviral machinery. It also describes some molecules that modify the levels of oxidative stress in HCV-infected cells.

Keywords: Hepatitis C virus, Oxidative stress, Reactive oxygen species, Vitamin E, Antioxidants, Glycyrrhizin, S-adenosylmethionine, N-acetylcysteine, Silymarin

Core tip: This review focuses on the available findings regarding the relationship between viral and cellular proteins and the resulting regulation of oxidative stress. To understand the liver damage induced by hepatitis C virus and its persistence is important to know how the cell regulatory systems involved in the production and elimination of reactive oxygen species (ROS) benefit the replication of the virus, as well as their participation in the cell defense mechanisms and immune perturbation following the infection. We must also consider the involvement of ROS in signaling pathways that induce viral replication and its implication in antiviral therapies.