Abstract
Cellular metabolic changes during chronic kidney disease (CKD) may induce higher production of oxygen radicals that play a significant role in the progression of renal damage and in the onset of important comorbidities. This condition seems to be in part related to dysfunctional mitochondria that cause an increased electron “leakage” from the respiratory chain during oxidative phosphorylation with a consequent generation of reactive oxygen species (ROS).ROS are highly active molecules that may oxidize proteins, lipids and nucleic acids with a consequent damage of cells and tissues.To mitigate this mitochondria-related functional impairment, a variety of agents (including endogenous and food derived antioxidants, natural plants extracts, mitochondria-targeted molecules) combined with conventional therapies could be employed.However, although the anti-oxidant properties of these substances are well known, their use in clinical practice has been only partially investigated. Additionally, for their correct utilization is extremely important to understand their effects, to identify the correct target of intervention and to minimize adverse effects.Therefore, in this manuscript, we reviewed the characteristics of the available mitochondria-targeted anti-oxidant compounds that could be employed routinely in our nephrology, internal medicine and renal transplant centers. Nevertheless, large clinical trials are needed to provide more definitive information about their use and to assess their overall efficacy or toxicity.
Highlights
Several authors have reported that in chronic kidney disease (CKD), even in the early stage, there is an abundant production of reactive oxygen species (ROS) [7] mainly due to an hyperactivation of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase [8,9,10], elevated synthesis of oxidative stress markers [e.g., F2-isoprostanes, malondialdehyde
This causes a drop in ATP production and exacerbates oxidative stress because these dysfunctional organelles release a great amount of ROS
That Alpha-lipoic acid (ALA) decreases vascular calcification by reducing vascular smooth muscle cells (VSMC) apoptosis by preserving anti-oxidant mitochondrial functions and activating Akt [109]. All these biochemical effects confer to this cofactor important antioxidant properties [110] that can be exploited in CKD patients to slow down the progression of renal damage and to control the onset of severe cardiovascular complications
Summary
Chronic Kidney Disese (Ckd) During CKD, the progressive deterioration of renal function [1] induces several biological and clinical dysfunctions including alteration in cellular energetic metabolism, change in nitrogen input/output, protein malnutrition, resistance to insulin and considerable enhancement of synthesis of inflammation/oxidative stress mediators [2,3,4,5,6]. Our group has recently demonstrated that the activity of Complex IV (a key regulator of respiratory chain activity) is reduced in PBMC of CKD/HD patients [49] This causes a drop in ATP production and exacerbates oxidative stress because these dysfunctional organelles release a great amount of ROS. Nuclear factor erythroid 2-related factor 2 (NRF-2) and one of its target gene superoxide dismutase 2 (SOD2) were up-regulated in peritoneal dialysistreated patients in the attempt to neutralize ROS over-production Whether these mitochondrial abnormalities represent a causative factor or an outcome of cellular injury during this process remains to be investigated.
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