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Introduction Glutathione is a tripeptide found in many tissues at relatively high concentrations, namely 110 mM in cells, similarly to glucose, potassium, and cholesterol, with a critical role in several physiological processes, such as redox balance preservation, reduction of oxidative stress through detoxification from xenobiotic and endogenous compounds, and immune system modulation ( Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, characterized by an excessive hepatic fat accumulation in the absence of alcoholic abuse, steatogenic medications or others concomitant liver diseases ( Although the pathogenic role of oxidative stress in NAFLD pathogenesis is well established ( 2

GSSG (oxidised glutathione) is the disulphide-linked dimer formed when two GSH molecules donate electrons

G., Ohura, T., & Gaustadnes, M

The oxidative damages of biomolecules specifically of DNA due to the accumulation of hydroperoxides and other ROS ultimately lead to the loss of cell viability or cell death through various death mechanisms like apoptosis, autophagy, necrosis, ferroptosis, and mitotic catastrophe (Fig

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S2), clearly demonstrating that uncatalyzed glutathionylation of regular protein thiols occurs much too slowly at low physiological GSSG concentrations to compete with glutaredoxin-dependent glutathionylation 63