The roles of oxidative stress and antioxidant. Treatment in experimental diabetic neuropathy

Phillip Anson Low, Kim K. Nickander, Hans J. Tritschler

Research output: Contribution to journalArticle

354 Citations (Scopus)

Abstract

Oxidative stress is present in the diabetic state. Our work has focused on its presence in peripheral nerves. Antioxidant enzymes are reduced in peripheral nerves and are further reduced in diabetic nerves. That lipid peroxidation will cause neuropathy is supported by evidence of the development of neuropathy de novo when normal nerves are rendered α- tocopherol deficient and by the augmentation of the conduction deficit in diabetic nerves subjected to this insult. Oxidative stress appears to be primarily due to the processes of nerve ischemia and hyperglycemia auto- oxidation. The indexes of oxidative stress include an increase in nerve, dorsal root, and sympathetic ganglia lipid hydroperoxides and conjugated dienes. The most reliable and sensitive index, however, is a reduction in reduced glutathione. Experimental diabetic neuropathy results in myelinopathy of dorsal roots and a vacuolar neuropathy of dorsal root ganglion. The vacuoles are mitochondrial; we posit that lipid peroxidation causes mitochondrial DNA mutations that increase reduced oxygen species, causing further damage to mitochondrial respiratory chain and function and resulting in a sensory neuropathy. α-lipoic acid is a potent antioxidant that prevents lipid peroxidation in vitro and in vivo. We evaluated the efficacy of the drug in doses of 20, 50, and 100 mg/kg administered intraperitoneally in preventing the biochemical, electrophysiological, and nerve blood flow deficits in the peripheral nerves of experimental diabetic neuropathy. α- lipoic acid dose- and time-dependently prevented the deficits in nerve conduction and nerve blood flow and biochemical abnormalities (reductions in reduced glutathione and lipid peroxidation). The nerve blood flow deficit was 50% (P < 0.001). Supplementation dose-dependently prevented the deficit; at the highest concentration, nerve blood flow was not different from that of control nerves. Digital nerve conduction underwent a dose-dependent improvement at 1 month (P < 0.05). By 3 months, all treated groups had lost their deficit. The antioxidant drug is potentially efficacious for human diabetic sensory neuropathy.

Original languageEnglish (US)
JournalDiabetes
Volume46
Issue numberSUPPL. 2
StatePublished - Sep 1997

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Diabetic Neuropathies
Lipid Peroxidation
Oxidative Stress
Antioxidants
Peripheral Nerves
Thioctic Acid
Neural Conduction
Spinal Ganglia
Glutathione
Sympathetic Ganglia
Tocopherols
Spinal Nerve Roots
Lipid Peroxides
Electron Transport
Vacuoles
Mitochondrial DNA
Hyperglycemia
Pharmaceutical Preparations
Ischemia
Oxygen

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

The roles of oxidative stress and antioxidant. Treatment in experimental diabetic neuropathy. / Low, Phillip Anson; Nickander, Kim K.; Tritschler, Hans J.

In: Diabetes, Vol. 46, No. SUPPL. 2, 09.1997.

Research output: Contribution to journalArticle

Low, Phillip Anson ; Nickander, Kim K. ; Tritschler, Hans J. / The roles of oxidative stress and antioxidant. Treatment in experimental diabetic neuropathy. In: Diabetes. 1997 ; Vol. 46, No. SUPPL. 2.
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