Targeting Oxidative Stress for the Treatment of Liver Fibrosis

Theerut Luangmonkong, Su Suriguga, Henricus A. M. Mutsaers, Geny M. M. Groothuis, Peter Olinga*, Miriam Boersema

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

61 Citaten (Scopus)

Samenvatting

Oxidative stress is a reflection of the imbalance between the production of reactive oxygen species (ROS) and the scavenging capacity of the antioxidant system. Excessive ROS, generated from various endogenous oxidative biochemical enzymes, interferes with the normal function of liver-specific cells and presumably plays a role in the pathogenesis of liver fibrosis. Once exposed to harmful stimuli, Kupffer cells (KC) are the main effectors responsible for the generation of ROS, which consequently affect hepatic stellate cells (HSC) and hepatocytes. ROS-activated HSC undergo a phenotypic switch and deposit an excessive amount of extracellular matrix that alters the normal liver architecture and negatively affects liver function. Additionally, ROS stimulate necrosis and apoptosis of hepatocytes, which causes liver injury and leads to the progression of end-stage liver disease. In this review, we overview the role of ROS in liver fibrosis and discuss the promising therapeutic interventions related to oxidative stress. Most importantly, novel drugs that directly target the molecular pathways responsible for ROS generation, namely, mitochondrial dysfunction inhibitors, endoplasmic reticulum stress inhibitors, NADPH oxidase (NOX) inhibitors, and Toll-like receptor (TLR)-affecting agents, are reviewed in detail. In addition, challenges for targeting oxidative stress in the management of liver fibrosis are discussed.

Originele taal-2English
TitelReviews of Physiology, Biochemistry and Pharmacology
RedacteurenB Nilius, P DeTombe, T Gudermann, R Jahn, R Lill
Plaats van productieCham
UitgeverijSpringer-Verlag Berlin Heidelberg
Pagina's71-102
Aantal pagina's32
ISBN van elektronische versie978-3-319-95288-8
ISBN van geprinte versie978-3-319-95287-1
DOI's
StatusPublished - 2018

Publicatie series

NaamReviews of Physiology Biochemistry and Pharmacology
UitgeverijSPRINGER-VERLAG BERLIN
Volume175
ISSN van geprinte versie0303-4240

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