Oxidative Stress, Apoptosis, and Mitochondrial Function in Diabetic Nephropathy.

Sonia Sifuentes-Franco,Sandra Carrillo-Ibarra,Alejandra Guillermina Miranda-Díaz,Diego Enrique Padilla-Tejeda

doi:10.1155/2018/1875870

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.

Highlights

The global prevalence of diabetes mellitus (DM) in adults has increased considerably in recent decades
Because the mechanisms in the appearance of diabetic nephropathy (DN) have not yet been fully described, we proposed the approach of looking at diverse themes including the epidemiology, the mechanism of appearance, and the role of oxidative stress (OS), the oxidative DNA damage, mitochondrial function, and cell death due to apoptosis in DN
Diabetic nephropathy is a microangiopathy that is prevalent in patients with type 1 and type 2 DM

Summary

Introduction

The global prevalence of diabetes mellitus (DM) in adults has increased considerably in recent decades. The RAAS inhibitors, including the ACEi and the ANG II receptor blockers, are both widely utilized to control arterial hypertension in diabetic patients These medications are considered superior to other categories of antihypertensive medications in the treatment of DN due to their capacity to reduce the intraglomerular pressure and prevent proteinuria by favoring the dilation of the efferent glomerular arteriole. In a recent meta-analysis, the authors published that statins significantly reduce albuminuria, the rate of excretion of urinary albumin, that the efficacy of renal function is dependent on the length of history of DM, and that the effect is better in type 2 DM with nephropathy [89]. The administration of COX-2 inhibitors for the treatment of DN continues to be controversial

Diabetic Nephropathy Treatment Future Perspectives

Findings

Conclusion