Hepatic antioxidant defense system

The hepatic antioxidant defense system is a complex network of enzymatic and non-enzymatic components designed to protect the liver from oxidative damage caused by reactive oxygen species (ROS) and reactive nitrogen species (RNS) [1, 9]. Key enzymatic members include superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), while non-enzymatic components include reduced glutathione (GSH), vitamin C, and vitamin E [1, 2]. This system is primarily regulated by the transcription factor Nrf2, which orchestrates the expression of cytoprotective genes in response to oxidative stress [9, 11]. In various liver diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD), alcoholic liver disease, and viral hepatitis, the balance between ROS production and antioxidant capacity is disrupted, leading to lipid peroxidation, protein oxidation, and DNA damage [9, 16]. Therapeutic strategies often aim to bolster this system through the administration of exogenous antioxidants like N-acetylcysteine or the use of Nrf2 activators to induce endogenous enzyme production [5, 18]. However, clinical translation has been challenging, as excessive antioxidant supplementation can sometimes interfere with essential ROS-mediated signaling pathways or exhibit pro-oxidant effects [18]. Understanding the spatial and temporal regulation of these defenses remains critical for developing effective hepatoprotective therapies [12].

Other names

Liver antioxidant systemHepatic antioxidant mechanismsHepatic redox defense systemEndogenous hepatic antioxidants

Activation of the Nrf2-ARE pathway to induce antioxidant enzyme expression, direct scavenging of reactive oxygen species, and replenishment of endogenous antioxidant pools like glutathione [9, 11].