Changes in Glutathione Content in Liver Diseases: An Update

Abstract

Glutathione (GSH), a tripeptide particularly concentrated in the liver, is the most important thiol reducing agent involved in the modulation of redox processes. It has also been demonstrated that GSH cannot be considered only as a mere free radical scavenger but that it takes part in the network governing the choice between survival, necrosis and apoptosis as well as in altering the function of signal transduction and transcription factor molecules. The purpose of the present review is to provide an overview on the molecular biology of the GSH system; therefore, GSH synthesis, metabolism and regulation will be reviewed. The multiple GSH functions will be described, as well as the importance of GSH compartmentalization into distinct subcellular pools and inter-organ transfer. Furthermore, we will highlight the close relationship existing between GSH content and the pathogenesis of liver disease, such as non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), chronic cholestatic injury, ischemia/reperfusion damage, hepatitis C virus (HCV), hepatitis B virus (HBV) and hepatocellular carcinoma. Finally, the potential therapeutic benefits of GSH and GSH-related medications, will be described for each liver disorder taken into account.

Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes

“…Therefore, the increased GPx activity could be the compensatory mechanism of the lowered CAT activity [50], but also a sign of increased H 2 O 2 production, as has been seen in activated hepatic stellate cells [55]. The GPx relies on the steady supply of GSH, using it as the reducing substrate in its peroxidase activity [56]. However, once the GPx peroxidase activity has been accomplished, it is up to the GR to re-reduced oxidised glutathione to the GSH [57].…”

Non-Alcoholic Fatty Liver Disease in Children

“…It is especially abundant in the liver. Fatty acid accumulation in the liver parenchyma leads to an increased metabolism and reactive oxygen species production, which is at first compensated by higher levels of glutathione, and probably presents the next step in NAFLD progression [ 23 ].…”

The Link between Type 2 Diabetes Mellitus and the Polymorphisms of Glutathione-Metabolizing Genes Suggests a New Hypothesis Explaining Disease Initiation and Progression

“…Certain clinical and experimental studies have already established that replenishing the endogenous deficiency of glutathione is a promising strategy in the treatment and prevention of type 2 diabetes and its complications [ 66 , 68 , 160 , 161 ]. We believe that polymorphisms of genes encoding glutathione-metabolizing enzymes represent attractive biomarkers for the predictive genetic testing of impaired glutathione metabolism and could be used for assessing the susceptibility of an individual to numerous pathological conditions associated with glutathione deficiency such as diabetes [ 27 , 30 ], cardiovascular diseases [ 162 , 163 ], cancer [ 164 ], liver diseases [ 165 ], neurodegenerative disorders [ 166 ] as well as COVID-19 [ 167 , 168 ]. Genetic polymorphisms of GSS and GGT7 and other glutathione-metabolizing enzymes may become attractive markers for pharmacogenetic studies of type 2 diabetes and its complications [ 169 , 170 ] and further studies are required to focus on a comprehensive evaluation of genes affecting glutathione metabolism for their joint effects on glutathione metabolism and their contribution to the development and progression of type 2 diabetes.…”