Targeting Oxidative Stress for the Treatment of Liver FibrosisLuangmonkong, T., Suriguga, S., Mutsaers, H. A. M., Groothuis, G. M. M., Olinga, P. & Boersema, M., 2018, Reviews of Physiology, Biochemistry and Pharmacology. Nilius, B., DeTombe, P., Gudermann, T., Jahn, R. & Lill, R. (eds.). Cham: Springer-Verlag Berlin Heidelberg, p. 71-102 32 p. (Reviews of Physiology Biochemistry and Pharmacology; vol. 175).
Research output: Chapter in Book/Report/Conference proceeding › Chapter › Academic › peer-review
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.
|Title of host publication||Reviews of Physiology, Biochemistry and Pharmacology|
|Editors||B Nilius, P DeTombe, T Gudermann, R Jahn, R Lill|
|Place of Publication||Cham|
|Publisher||Springer-Verlag Berlin Heidelberg|
|Number of pages||32|
|Publication status||Published - 2018|
|Name||Reviews of Physiology Biochemistry and Pharmacology|
- Liver fibrosis, Oxidative stress, Reactive oxygen species, Therapeutic target, ENDOPLASMIC-RETICULUM STRESS, TOLL-LIKE RECEPTOR, EIF2-ALPHA DEPHOSPHORYLATION INHIBITOR, OXYGEN SPECIES PRODUCTION, HEPATIC STELLATE CELLS, DOUBLE-BLIND, MITOCHONDRIAL DYSFUNCTION, NADPH OXIDASES, IN-VIVO, COENZYME-Q10 SUPPLEMENTATION