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Targeting oxidative stress and anti-oxidant defence in diabetic kidney disease

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Abstract

There is an unmet need for new strategies to prevent or postpone the development of diabetic kidney disease. The pathophysiology of this condition includes as a central mechanism an imbalance between the excessive production of reactive oxygen species (ROS) and inadequate anti-oxidant defense. Reduction of ROS is therefore an interesting therapeutic target that warrants further investigation. Herein, we review the drivers of oxidative stress in diabetic kidney disease including NADPH oxidases, mitochondrial ROS production, xanthine oxidase, cytochrome P450, uncoupled eNOS and lipoxygenase. Secondly, the role of anti-oxidative mechanisms in diabetic kidney disease is discussed including the role of the kelch-like ECH-associated protein 1- nuclear factor erythroid 2-related factor 2, lipoxin, oral anti-oxidants and glutathione peroxidase-1. We will also review data supporting the concept that the beneficial renal effects of anti-diabetic drugs that target the glucagon-like peptide 1 receptor and the sodium glucose transporter 2 are, at least in part, due to their impact on oxidative stress in diabetic kidney disease. In the present article we critically evaluate both preclinical studies with cell culture experiments and animal models of diabetic kidney disease as well as covering the current findings from clinical studies addressing targeted interventions towards these pathways.

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Authors and Affiliations

  1. Department of Diabetes, Central Clinical School, Monash University, The Alfred Centre, Level 5, 99 Commercial Road, Melbourne, VIC, 3004, Australia

    Jakob Appel Østergaard, Mark Emmanuel Cooper & Karin Agnes Maria Jandeleit-Dahm

  2. Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

    Jakob Appel Østergaard

  3. Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark

    Jakob Appel Østergaard

  4. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes, Research at Heinrich-Heine University, Düsseldorf, Germany

    Karin Agnes Maria Jandeleit-Dahm

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  1. Jakob Appel Østergaard
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Østergaard, J.A., Cooper, M.E. & Jandeleit-Dahm, K.A.M. Targeting oxidative stress and anti-oxidant defence in diabetic kidney disease. J Nephrol 33, 917–929 (2020). https://doi.org/10.1007/s40620-020-00749-6

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