Publication: Targeting oxidative stress for the treatment of liver fibrosis
Issued Date
2018-01-01
Resource Type
ISSN
16175786
03034240
03034240
Other identifier(s)
2-s2.0-85052682553
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Reviews of Physiology, Biochemistry and Pharmacology. Vol.175, (2018), 71-102
Suggested Citation
Theerut Luangmonkong, Su Suriguga, Henricus A.M. Mutsaers, Geny M.M. Groothuis, Peter Olinga, Miriam Boersema Targeting oxidative stress for the treatment of liver fibrosis. Reviews of Physiology, Biochemistry and Pharmacology. Vol.175, (2018), 71-102. doi:10.1007/112_2018_10 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/45309
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Targeting oxidative stress for the treatment of liver fibrosis
Other Contributor(s)
Abstract
© 2018, Springer International Publishing AG, part of Springer Nature. 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.