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Cited by 300Nitric Oxide and Endothelin EffectsAldose Reductase and TaurineBiochemical Acid Research Studies

Effect of Antioxidant Treatment of Streptozotocin-Induced Diabetic Rats on Endoneurial Blood Flow, Motor Nerve Conduction Velocity, and Vascular Reactivity of Epineurial Arterioles of the Sciatic Nerve

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Coppey, Lawrence J., Gellett, Jill S., Davidson, Eric P., Dunlap, Joyce A., Lund, Donald D., Yorek, Mark A.·2001·Diabetes
DOI 10.2337/diabetes.50.8.1927
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Abstract

We have shown that diabetes-induced reduction in endoneurial blood flow (EBF) and impaired endothelium-dependent vascular relaxation precede slowing of motor nerve conduction velocity (MNCV) and decreased sciatic nerve Na+/K+ ATPase activity. Furthermore, vascular dysfunction was accompanied by an accumulation of superoxide in arterioles that provide circulation to the sciatic nerve. In the present study, we examined the effect that treatment of streptozotocin-induced diabetic rats with antioxidants has on vascular and neural function. Diabetic rats were treated with 0.5% α-lipoic acid as a diet supplement or with hydroxyethyl starch deferoxamine (HES-DFO) by weekly intravenous injections at a dose of 75 mg/kg. The treatments significantly improved diabetes-induced decrease in EBF, acetylcholine-mediated vascular relaxation in arterioles that provide circulation to the region of the sciatic nerve, and MNCV. The treatments also reduced the production of superoxide by the aorta and superoxide and peroxynitrite by arterioles that provide circulation to the region of the sciatic nerve. Treating diabetic rats with α-lipoic acid prevented the diabetes-induced increase in thiobarbituric acid–reactive substances in serum and significantly improved lens glutathione levels. In contrast, treating diabetic rats with HES-DFO did not prevent diabetes-induced changes of either of these markers of oxidative stress. Diabetes-induced increase in sciatic nerve conjugated diene levels was not improved by treatment with either α-lipoic acid or HES-DFO. Treating diabetic rats with α-lipoic acid but not HES-DFO partially improved sciatic nerve Na+/K+ ATPase activity and myo-inositol content. The increase in sciatic nerve sorbitol levels in diabetic rats was unchanged by either treatment. These studies suggest that diabetes-induced oxidative stress and the generation of superoxide may be partially responsible for the development of diabetic vascular and neural complications.

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  • Increased oxidative stress contributes to diabetes-induced vascular and neural disease.

    “Further, treating diabetic rats with three different types of antioxidants prevented the diabetes-induced increase in superoxide and peroxynitrite formation in aorta and epineurial arterioles of the sciatic nerve and diabetes-induced vascular and neural dysfunction, thereby providing evidence that increased oxidative stress contributes to diabetes-induced vascular and neural disease (67–69).”

    From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [68]

  • Treating diabetic rats with three different types of antioxidants prevented the diabetes-induced increase in superoxide and peroxynitrite formation in aorta and epineurial arterioles of the sciatic nerve and diabetes-induced vascular and neural dysfunction.

    “Further, treating diabetic rats with three different types of antioxidants prevented the diabetes-induced increase in superoxide and peroxynitrite formation in aorta and epineurial arterioles of the sciatic nerve and diabetes-induced vascular and neural dysfunction, thereby providing evidence that increased oxidative stress contributes to diabetes-induced vascular and neural disease (67–69).”

    From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [68]

  • Generation of oxidative stress through superoxide and peroxynitrite impairs vascular function and endothelium-dependent vascular relaxation in epineural arterioles of the sciatic nerve from diabetic rats.

    “Studies in our laboratory of epineural arterioles of the sciatic nerve derived from diabetic rats have provided evidence that the generation of oxidative stress through the production of superoxide and peroxynitrite impairs vascular function and endothelium-dependent vascular relaxation (67–69, 342).”

    From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [68]

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Authors
Coppey, L. J., Gellett, J. S., Davidson, E. P., Dunlap, J. A., Lund, D. D., & Yorek, M. A.
Affiliations
University of Iowa (US)
ORCID
Yorek, Mark A.
Venue
Diabetes
Publisher
American Diabetes Association
Published
2001-08-01
Volume
50
Issue
8
Pages
1927-1937
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/diabetes.50.8.1927
OpenAlex
W2147294760
Cited by
300
References
63
Citations by year
2026: 4 · 2025: 5 · 2024: 8 · 2023: 6 · 2022: 6 · 2021: 10 · 2020: 6 · 2019: 9 · 2018: 7 · 2017: 16 · 2016: 8 · 2015: 13 · 2014: 10 · 2013: 17 · 2012: 18
FWCI
8.78
Type
journal article
Language
en
Open access
Locations
  • Diabetes (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Diabetes Association
  • U.S. Department of Veterans Affairs (DK-25295)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK-25295, DK-58005, P30DK025295)
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Biochemical Acid Research Studies
Keywords
streptozotocin-induced diabetes, antioxidant treatment, alpha-lipoic acid, motor nerve conduction velocity, sciatic nerve, superoxide, peroxynitrite, oxidative stress, Na+/K+-ATPase, myo-inositol, sorbitol, diabetic vascular complications, diabetic neuropathy, glutathione, lipid peroxidation
MeSH terms
Sodium-Potassium-Exchanging ATPase, Animals, Antioxidants, Aorta, Arterioles, Diabetes Mellitus, Experimental, Inositol, Thioctic Acid, Male, Motor Neurons, Muscle, Smooth, Vascular, Neural Conduction, Nitrates, Reference Values, Regional Blood Flow, Sciatic Nerve, Sorbitol, Superoxides, Vasodilation, Rats, Sprague-Dawley, Microscopy, Video, Dietary Supplements, Rats

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