Oxidative stress, apoptosis, and mitochondrial function in diabetic nephropathy

Abstract

Diabetic nephropathy (DN) is the second most frequent and prevalent complication of diabetes mellitus (DM). The increase in the production of oxidative stress (OS) is induced by the persistent hyperglycemic state capable of producing oxidative damage to the macromolecules (lipids, carbohydrates, proteins, and nucleic acids). OS favors the production of oxidative damage to the histones of the double-chain DNA and affects expression of the DNA repairer enzyme which leads to cell death from apoptosis. The chronic hyperglycemic state unchains an increase in advanced glycation end-products (AGE) that interact through the cellular receptors to favor activation of the transcription factor NF-κB and the protein kinase C (PKC) system, leading to the appearance of inflammation, growth, and augmentation of synthesis of the extracellular matrix (ECM) in DN. The reactive oxygen species (ROS) play an important role in the pathogenesis of diabetic complications because the production of ROS increases during the persistent hyperglycemia. The primary source of the excessive production of ROS is the mitochondria with the capacity to exceed production of endogenous antioxidants. Due to the fact that the mechanisms involved in the development of DN have not been fully clarified, there are different approaches to specific therapeutic targets or adjuvant management alternatives in the control of glycemia in DN.