Role of oxidative stress in diabetic nephropathy

Josephine M. Forbes, Melinda T. Coughlan, Mark E. Cooper

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Other


Oxidative stress, occurs primarily as the result of normal metabolism but is facilitated by the conditions present in a number of chronic disorders, including diabetic nephropathy (DN). It is postulated, that oxidative stress is an early link between hyperglycaemia and renal disease but also likely occurs as a consequence of other primary pathogenic mechanisms seen in diabetes. There are a number of pathways which generate reactive oxygen species (ROS) in the kidney such as glycolysis, specific defects in the polyol pathway, uncoupling of nitric oxide synthase, xanthine oxidase, NAD(P)H oxidase and advanced glycation which have each been identified as potentially major contributors to the pathogenesis of diabetic kidney disease. In addition, mitochondrial production of ROS in response to chronic hyperglycaemia may also be a key contributor to each of these pathogenic pathways. To date, it is unclear as to why antioxidants per se have demonstrated such poor renoprotection in humans, despite exciting positive preclinical research findings, however, it seems evident that therapies such as vitamins may not be the ideal antioxidant strategy in human diabetic nephropathy. More recent data have suggested that combined strategies involving a more targeted antioxidant approach, using agents which penetrate specific cellular compartments, may be the elusive additive therapy required to optimise renoprotection in diabetes.

Original languageEnglish
Title of host publicationAdvances in Pathogenesis of Diabetic Nephropathy
EditorsSharma S. Prabhakar
PublisherNova Science Publishers
Number of pages20
ISBN (Print)9781611221343
Publication statusPublished - 2011


  • Diabetes complications
  • Mitochondria
  • Mitochondrial dysfunction
  • NADPH oxidase
  • Reactive oxygen species

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