Oxidative stress in the pathogenesis/treament of diabetes and its complications

Ludovica Piconi, Michael A. Ihnat, Antonio Ceriello

Research output: Contribution to journalArticlepeer-review

Abstract

In diabetes oxidative stress plays a key role in the pathogenesis of vascular complications, and an early step of such damage is considered the development of an endothelial dysfunction. Hyperglycemia directly promotes an endothelial dysfunction inducing process of overproduction of superoxide and consequently peroxynitrite that damages DNA and activates the nuclear enzyme poly(ADP-ribose) polymerase. This process, depleting NAD+, slowing glycolisis, ATP formation and electron transport, results in acute endothelial dysfunction in diabetic blood vessels and contributes to the development of diabetic complications. These new findings may explain why classical antioxidants, like vitamin E, that work scavenging already formed toxic oxidation products, have failed to show beneficial effects on diabetic complications, and suggest new and attractive "causal" antioxidant therapy. New, low molecular mass compounds that act as SOD or catalase mimetics or L-propionyl-carnitine and lipoic acid, that work as intracellular superoxide scavengers, improving mitochondrial function and reducing DNA damage, may be good candidates for such strategy, and preliminary studies support this hypothesis. This "causal" therapy would also be associated with other promising tools such as LY 333531, PJ34 and FP15, which block protein kinase β isoform, poly(ADP-ribose) polymerase and peroxynitrite, respectively. It is now evident that, statins, ACE inhibitors, AT-1 blockers, calcium channel blockers and thiazolinediones have a strong intracellular antioxidant activity, and it has been suggested that many of their beneficial ancillary effects are due to this property. This preventive activity against oxidative stress generation can justify a large utilization and association of this compounds for preventing complications in diabetic patients where antioxidant defences have been shown to be defective.

Original languageEnglish
Pages (from-to)194-199
Number of pages6
JournalCurrent Nutrition and Food Science
Volume3
Issue number3
DOIs
Publication statusPublished - Aug 2007

Keywords

  • Aldose reductase
  • Hexosamine Pathway
  • Polyol Pathway
  • Protein kinase C
  • Reactive oxygen species

ASJC Scopus subject areas

  • Nutrition and Dietetics
  • Public Health, Environmental and Occupational Health
  • Food Science

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