The Nrf2 has been identified as a key molecular player in orchestrating adaptive cellular interactions following a wide spectrum of cellular conditions that could be either extracellular or intracellular. The encoded transcription factor regulates genes, which contain antioxidant response elements (ARE) in their promoters; many of these genes encode proteins involved in response to environmental stress, detoxifying enzymes, metabolic enzymes, injury, and inflammation, which includes the production of free radicals. The association between oxidative stress and inflammation with progression of diabetic nephropathy and cardiomyopathy has been described. The prevention of diabetic nephropathy and cardiomyopathy has become a global concern for those who are working in diabetic care management. Therefore, activation of Nrf2 has the potential to protect against macromolecular damage. Studies have demonstrated the beneficial role of Nrf2 induction in the prevention of DN. Upon exposure of cells to oxidative stress or electrophilic compounds, Nrf2 dissociates from Keap1 and translocates into the nucleus to bind to antioxidant-responsive elements in the genes encoding antioxidant enzymes. Upregulation of these Nrf2-dependent antioxidants promotes detoxification and anti-inflammatory function. Thus, the Nrf2 activators have been suggested for preventing diabetic nephropathy.
Part of the book: The Transcription Factor Nrf2
Pancreatic β cells are more sensitive to cytotoxic stress than several other cells due to the expression of very low levels of antioxidant enzymes. Glutathione-S-transferase (GST) is a detoxification enzyme essential for a cellular protection against oxidative damage. Thus, the objective of this chapter is to verify the impact of the hypothesis of all effects of Glutathione S-transferase polymorphism in patients with diabetic complications. Diabetic nephropathy (DN) is the main secondary complication of diabetes mellitus (DM). Notably, the expression of GST genes has been described in different variations as ethnic populations. Some studies have suggested association between genetic polymorphism for GSTM1, GSTT1 and GSTP1 and DN, but others do not. The results are still inconsistent and, therefore, more studies are needed to be performed.
Part of the book: Glutathione in Health and Disease