Effects of antioxidants on nerve and vascular dysfunction in experimental diabetes

Norman E Cameron, M A Cotter

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

Reactive oxygen species (ROS) are elevated by metabolic changes in diabetes, including autoxidation and increased advanced glycation. Endogenous protection by the glutathione redox cycle is also compromised by the competing NADPH requirement of elevated polyol pathway flux. Antioxidant treatment strategies prevent or reverse nerve conduction velocity (NCV) deficits in diabetic rats. These include lipophilic scavengers such as butylated hydroxytoluene, probucol and Vitamin E, more hydrophilic agents like alpha-lipoic acid and acetyl cysteine, and transition metal chelators that inhibit autoxidation. In the long-term, elevated ROS cause cumulative damage to neurons and Schwann cells, however, they also have a deleterious effect on nerve blood flow in the short term. This causes endoneurial hypoxia, which is responsible for early NCV deficits. Antioxidant treatment corrects the blood flow deficit and promotes normal endoneurial oxygenation. ROS cause antioxidant-preventable vascular endothelium abnormalities, neutralizing nitric oxide mediated vasodilation and increasing reactivity to vasoconstrictors. Unsaturated fatty acids are a major target for ROS and essential fatty acid metabolism is impaired by diabetes. gamma-Linolenic acid stimulates vasodilator prostanoid production, and there are marked synergistic interactions between gamma-linolenic acid and antioxidants. This has encouraged the development of novel drugs such as ascorbyl-gamma-linoIenic acid and gamma-linolenic acid-lipoic acid with enhanced therapeutic potential. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)137-146
Number of pages10
JournalDIABETES RESEARCH AND CLINICAL PRACTICE
Volume45
Publication statusPublished - 1999

Keywords

  • diabetes
  • neuropathy
  • nerve conduction velocity
  • blood flow
  • ischemia
  • antioxidant
  • free radicals
  • nitric oxide
  • vascular endothelium
  • vitamin E
  • alpha-lipoic acid
  • ALPHA-LIPOIC ACID
  • ENDOTHELIUM-DEPENDENT RELAXATION
  • ESSENTIAL FATTY-ACIDS
  • BLOOD-FLOW
  • PERIPHERAL-NERVE
  • NITRIC-OXIDE
  • OXIDATIVE STRESS
  • NEUROVASCULAR FUNCTION
  • CONDUCTION VELOCITY
  • TREATMENT PREVENTS

Cite this

Effects of antioxidants on nerve and vascular dysfunction in experimental diabetes. / Cameron, Norman E; Cotter, M A .

In: DIABETES RESEARCH AND CLINICAL PRACTICE, Vol. 45, 1999, p. 137-146.

Research output: Contribution to journalArticle

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AB - Reactive oxygen species (ROS) are elevated by metabolic changes in diabetes, including autoxidation and increased advanced glycation. Endogenous protection by the glutathione redox cycle is also compromised by the competing NADPH requirement of elevated polyol pathway flux. Antioxidant treatment strategies prevent or reverse nerve conduction velocity (NCV) deficits in diabetic rats. These include lipophilic scavengers such as butylated hydroxytoluene, probucol and Vitamin E, more hydrophilic agents like alpha-lipoic acid and acetyl cysteine, and transition metal chelators that inhibit autoxidation. In the long-term, elevated ROS cause cumulative damage to neurons and Schwann cells, however, they also have a deleterious effect on nerve blood flow in the short term. This causes endoneurial hypoxia, which is responsible for early NCV deficits. Antioxidant treatment corrects the blood flow deficit and promotes normal endoneurial oxygenation. ROS cause antioxidant-preventable vascular endothelium abnormalities, neutralizing nitric oxide mediated vasodilation and increasing reactivity to vasoconstrictors. Unsaturated fatty acids are a major target for ROS and essential fatty acid metabolism is impaired by diabetes. gamma-Linolenic acid stimulates vasodilator prostanoid production, and there are marked synergistic interactions between gamma-linolenic acid and antioxidants. This has encouraged the development of novel drugs such as ascorbyl-gamma-linoIenic acid and gamma-linolenic acid-lipoic acid with enhanced therapeutic potential. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.

KW - diabetes

KW - neuropathy

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KW - TREATMENT PREVENTS

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JO - DIABETES RESEARCH AND CLINICAL PRACTICE

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