TY - JOUR
T1 - Targeting oxidative stress and anti-oxidant defence in diabetic kidney disease
AU - Østergaard, Jakob Appel
AU - Cooper, Mark Emmanuel
AU - Jandeleit-Dahm, Karin Agnes Maria
PY - 2020/10
Y1 - 2020/10
N2 - 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.
AB - 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.
KW - ACCELERATED NEPHROPATHY
KW - Anti-oxidant defence
KW - BARDOXOLONE METHYL
KW - Diabetic nephropathy
KW - EXPERIMENTAL-MODEL
KW - GLYCATION END-PRODUCTS
KW - NADPH OXIDASE
KW - NITRIC-OXIDE SYNTHASE
KW - NLRP3 INFLAMMASOME
KW - NOX INHIBITOR
KW - Oxidative stress
KW - RENAL-DISEASE
KW - Reactive oxygen species
KW - SMALL-MOLECULE INHIBITOR
UR - http://www.scopus.com/inward/record.url?scp=85085303250&partnerID=8YFLogxK
U2 - 10.1007/s40620-020-00749-6
DO - 10.1007/s40620-020-00749-6
M3 - Review
C2 - 32447617
SN - 1121-8428
VL - 33
SP - 917
EP - 929
JO - Journal of Nephrology
JF - Journal of Nephrology
IS - 5
ER -