Effect of α-lipoic acid on vascular responses and nociception in diabetic rats
Abstract
Oxidative stress contributes to the vascular and neurological complications of diabetes mellitus. The aim was to evaluate the effects of treatment with the radical scavenger and transition metal chelator, alpha-lipoic acid, on endothelium-dependent relaxation of the mesenteric vasculature and on superior cervical ganglion blood flow in 8 week streptozotocin-induced diabetic rats. alpha-Lipoic acid effects on small nerve fiber-mediated nociception were also monitored. For the in vitro phenylephrine-precontracted mesenteric vascular bed, diabetes caused a 31% deficit in maximum endothelium-dependent relaxation to acetylcholine, and a 4-fold reduction in sensitivity. alpha-Lipoic acid gave 85% protection against these defects. Acetylcholine responses are mediated by nitric oxide and endothelium-derived hyperpolarizing factor: isolation of the latter by nitric oxide synthase blockade revealed a 74% diabetic deficit that was halved by alpha-lipoic acid. Superior cervical ganglion blood flow, 52% reduced by diabetes, was dose-dependently restored by alpha-lipoic acid (ED(50), 44 mg/kg/d). Diabetic rats exhibited mechanical and thermal hyperalgesia, which were abolished by alpha-lipoic acid treatment. Thus, diabetes impairs nitric oxide and endothelium-derived hyperpolarizing factor-mediated vasodilation. This contributes to reduced neural perfusion, and may be responsible for altered nociceptive function. The effect of alpha-lipoic acid strongly implicates oxidative stress in these events and suggests a potential therapeutic approach.
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Treating diabetic rats with α-lipoic acid or the metal chelators hydroxyethyl starch deferoxamine or trientine prevented the diabetes-induced impairment in vascular relaxation associated with hyperalgesia and neurovascular deficits.
“Cameron and colleagues (46, 48–50, 145) demonstrated that treating diabetic rats with α-lipoic acid or the metal chelators, hydroxyethyl starch deferoxamine or trientine, prevented the diabetes-induced impairment in vascular relaxation associated with hyperalgesia and neurovascular deficits.”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [50]
Formation of hydroxyl radicals also contributes to impairment of vascular reactivity and nerve function in diabetes.
“Because metal chelators and hydroxyl radical scavengers have also been demonstrated to be effective in preventing diabetes-induced vascular and neural dysfunction, it is likely that the formation of hydroxyl radicals also contributes to impairment of vascular reactivity and nerve function in diabetes (46–51, 145).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [50]
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Sivitz, W. I., & Yorek, M. A. (2010) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.2531 · Cited by 742 · see citing works
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- Authors
- Cameron, N.
- Affiliations
- University of Aberdeen (GB)
- Corresponding author
- Cameron, N
- ORCID
- Cameron, N
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2001-07-01
- Volume
- 31
- Issue
- 1
- Pages
- 125-135
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2120722543
- Cited by
- 83
- References
- 71
- Citations by year
- 2025: 1 · 2023: 1 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 2 · 2015: 7 · 2014: 6 · 2013: 4 · 2012: 5
- FWCI
- 1.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Biochemical Acid Research Studies
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
- Keywords
- alpha-lipoic acid, diabetes mellitus, oxidative stress, endothelium-dependent relaxation, mesenteric vasculature, acetylcholine, nitric oxide, endothelium-derived hyperpolarizing factor, streptozotocin-induced diabetes, diabetic vascular complications
- MeSH terms
- Animals, Antioxidants, Blood Flow Velocity, Diabetes Mellitus, Experimental, Endothelium, Vascular, Thioctic Acid, Male, Mesenteric Arteries, Muscle, Smooth, Vascular, Pain, Phenylephrine, Vasoconstrictor Agents, Vasodilation, Rats, Sprague-Dawley, Superior Cervical Ganglion, Rats
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