Nuclear Factor Erythroid 2-Related Factor 2 Versus Reactive Oxygen Species: Potential Therapeutic Approach on Fighting Liver Fibrosis

Lenny Setiawati; Isabella Kurnia Liem; Firda Asma'ul Husna

doi:10.3889/oamjms.2023.11334

Authors

Lenny Setiawati Department of Anatomy, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Master’s Programme in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Department of Anatomy, Faculty of Medicine, Universitas Trisakti, Jakarta, Indonesia https://orcid.org/0000-0002-7487-5948
Isabella Kurnia Liem Department of Anatomy, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia https://orcid.org/0000-0002-0138-2659
Firda Asma'ul Husna Department of Anatomy, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia https://orcid.org/0000-0001-6149-3054

DOI:

https://doi.org/10.3889/oamjms.2023.11334

Keywords:

HSC activation, liver fibrosis, mitochondrial dysfunction, Nrf2, ROS

Abstract

Chronic liver disease (CLD) is a progressive deterioration of the liver due to exposure to viruses, drugs, fat accumulation, and toxicity which lead to an imbalance between extracellular matrix accumulation and degradation. Accumulation of the extracellular matrix is a normal liver response at the beginning of the injury. However, increasing extracellular matrix accumulation leads to fibrosis, cirrhosis, and organ failure. Until today, liver transplant is the gold standard therapy for end-stage CLD. Unfortunately, the liver transplant itself faces difficulties such as finding a compatible donor and dealing with complications after treatment. This review provides further information about nuclear factor erythroid 2-related factor 2 (Nrf2) as an alternative approach to fight liver fibrosis. Transformation of hepatic stellate cell (HSC) to myofibroblast has been known as the main mechanism that occurs in fibrosis while epithelial-mesenchymal transition (EMT) and mitochondrial dysfunction become the mechanism followed. In these conditions, oxidative stress is the great promoter which builds a vicious cycle leading to CLD progressivity. Hence, Nrf2 as antioxidant regulator becomes the potential target to break the cycle. While reactive oxygen species (ROS) in oxidative stress induce HSC activation, EMT, and mitochondrial dysfunction through activation of many signaling pathways, Nrf2 acts to diminish ROS directly by regulating secreted antioxidants and its scavenging action. Nrf2 also inactivates fibrosis signaling pathways and plays a role in maintaining mitochondrial health. Therefore, Nrf2 can be a potential target for liver fibrosis therapy.

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