Free radicals, antioxidants, nuclear factor‐E2‐related factor‐2 and liver damage

Abstract

Oxidative/nitrosative stress is proposed to be a critical factor in various diseases, including liver pathologies. Antioxidants derived from medicinal plants have been studied extensively and are relevant to many illnesses, including liver diseases. Several hepatic disorders, such as viral hepatitis and alcoholic or nonalcoholic steatohepatitis, involve free radicals/oxidative stress as agents that cause or at least exacerbate liver injury, which can result in chronic liver diseases, such as liver fibrosis, cirrhosis and end‐stage hepatocellular carcinoma. In this scenario, nuclear factor‐E2‐related factor‐2 (Nrf2) appears to be an essential factor to counteract or attenuate oxidative or nitrosative stress in hepatic cells. In fact, a growing body of evidence indicates that Nrf2 plays complex and multicellular roles in hepatic inflammation, fibrosis, hepatocarcinogenesis and regeneration via the induction of its target genes. Inflammation is the most common feature of chronic liver diseases, triggering fibrosis, cirrhosis and hepatocellular carcinoma. Increasing evidence indicates that Nrf2 counteracts the proinflammatory process by modulating the recruitment of inflammatory cells and inducing the endogenous antioxidant response of the cell. In this review, the interactions between antioxidant and inflammatory molecular pathways are analyzed.

Omaveloxolone and TX63682 are hepatoprotective in the STAM mouse model of nonalcoholic steatohepatitis

“…[47] Thus, the overall hepatoprotective pharmacology of omaveloxolone and its analogs are consistent with the profound hepatoprotective properties of Nrf2, which has been studied and reviewed extensively. [21,[48][49][50][51][52] In conclusion, omaveloxolone and TX63682 demonstrated significant hepatoprotection in a rodent model of NASH. Such hepatoprotection was observed in conjunction with improvements in glucose control and lipid handling, which is consistent with the overall phenotype of improved mitochondrial function that is associated with Nrf2 activation.…”

Emerging Noninvasive Biomarkers, and Medical Management Strategies for Alcoholic Hepatitis: Present Understanding and Scope

“…Several antioxidants have been studied with respect to ALD, including vitamin E and glutathione. Multiple animal and human models have shown that free radicals and oxidative stress can cause or at least exacerbate liver injury in ALD [150,151]. Vitamin E is a first-line therapy for NASH [152].…”

Roles of Nrf2 in Liver Diseases: Molecular, Pharmacological, and Epigenetic Aspects

“…ROS include molecules derived from oxygen reduction, such as molecules or atoms that have unpaired electrons and are unstable and highly reactive because they can react with adjacent molecules subtracting electrons. Oxidative intermediaries can generally be classified into oxygen-centered radicals, such as superoxide radical, hydroxyl radical, and peroxyl radical, and oxygen-centered non-radicals, such as hydrogen peroxide and singlet oxygen [ 9 ]. Production of all these molecules is part of aerobic metabolism in humans, which, in a certain way, is important for some physiological functions such as signal transduction pathways and defense against microorganisms (neutrophils, eosinophils, and macrophages during inflammation), among others [ 10 ].…”