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      New Pathogenic Concepts and Therapeutic Approaches to Oxidative Stress in Chronic Kidney Disease

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          Abstract

          In chronic kidney disease inflammatory processes and stimulation of immune cells result in overproduction of free radicals. In combination with a reduced antioxidant capacity this causes oxidative stress. This review focuses on current pathogenic concepts of oxidative stress for the decline of kidney function and development of cardiovascular complications. We discuss the impact of mitochondrial alterations and dysfunction, a pathogenic role for hyperuricemia, and disturbances of vitamin D metabolism and signal transduction. Recent antioxidant therapy options including the use of vitamin D and pharmacologic therapies for hyperuricemia are discussed. Finally, we review some new therapy options in diabetic nephropathy including antidiabetic agents (noninsulin dependent), plant antioxidants, and food components as alternative antioxidant therapies.

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          Most cited references222

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          Mitochondrial dynamics--mitochondrial fission and fusion in human diseases.

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            PGC-1alpha: a key regulator of energy metabolism.

            Peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha is a member of a family of transcription coactivators that plays a central role in the regulation of cellular energy metabolism. It is strongly induced by cold exposure, linking this environmental stimulus to adaptive thermogenesis. PGC-1alpha stimulates mitochondrial biogenesis and promotes the remodeling of muscle tissue to a fiber-type composition that is metabolically more oxidative and less glycolytic in nature, and it participates in the regulation of both carbohydrate and lipid metabolism. It is highly likely that PGC-1alpha is intimately involved in disorders such as obesity, diabetes, and cardiomyopathy. In particular, its regulatory function in lipid metabolism makes it an inviting target for pharmacological intervention in the treatment of obesity and Type 2 diabetes.
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              Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis.

              During primate evolution, a major factor in lengthening life-span and decreasing age-specific cancer rates may have been improved protective mechanisms against oxygen radicals. We propose that one of these protective systems is plasma uric acid, the level of which increased markedly during primate evolution as a consequence of a series of mutations. Uric acid is a powerful antioxidant and is a scavenger of singlet oxygen and radicals. We show that, at physiological concentrations, urate reduces the oxo-heme oxidant formed by peroxide reaction with hemoglobin, protects erythrocyte ghosts against lipid peroxidation, and protects erythrocytes from peroxidative damage leading to lysis. Urate is about as effective an antioxidant as ascorbate in these experiments. Urate is much more easily oxidized than deoxynucleosides by singlet oxygen and is destroyed by hydroxyl radicals at a comparable rate. The plasma urate levels in humans (about 300 microM) is considerably higher than the ascorbate level, making it one of the major antioxidants in humans. Previous work on urate reported in the literature supports our experiments and interpretations, although the findings were not discussed in a physiological context.
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                Author and article information

                Journal
                Oxid Med Cell Longev
                Oxid Med Cell Longev
                OMCL
                Oxidative Medicine and Cellular Longevity
                Hindawi Publishing Corporation
                1942-0900
                1942-0994
                2016
                27 June 2016
                : 2016
                : 6043601
                Affiliations
                1Department of Biology, Faculty of Chemistry, UNAM, 04510 Mexico City, DF, Mexico
                2Laboratory of Renal Physiopathology, INC Ignacio Chávez, 14080 Mexico City, DF, Mexico
                3Department of Nephrology, INC Ignacio Chávez, 14080 Mexico City, DF, Mexico
                4Department of Nephrology, Odense University Hospital, 5000 Odense, Denmark
                5Institute of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark
                Author notes
                *Alexandra Scholze: ascholze@ 123456health.sdu.dk

                Academic Editor: Gabriele Saretzki

                Author information
                http://orcid.org/0000-0001-6628-4411
                http://orcid.org/0000-0002-9718-6854
                http://orcid.org/0000-0002-3100-8692
                Article
                10.1155/2016/6043601
                4939360
                27429711
                67f6472f-7949-4516-afa4-dcbf8026d179
                Copyright © 2016 José Pedraza-Chaverri et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 11 March 2016
                : 16 May 2016
                : 25 May 2016
                Categories
                Review Article

                Molecular medicine
                Molecular medicine

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