Journal article
Effect of Fidarestat andα-Lipoic Acid on Diabetes-Induced Epineurial Arteriole Vascular Dysfunction
Experimental diabesity research, Vol.5(2), pp.123-135
2004
DOI: 10.1080/15438600490277824
PMCID: PMC2496880
PMID: 15203883
Abstract
In the present study, the authors examined whether treating streptozotocin-induced diabetic rats with the combination ofα-lipoic acid and fidarestat, an aldose reductase inhibitor, can promote the formation of dihydrolipoic acid in diabetic animals and thereby enhance the efficacy ofα-lipoic acid as monotherapy toward preventing diabetic vascular and neural dysfunction.Treating diabetic rats with the combination of 0.25%α-lipoic acid (in the diet) and fidarestat (3 mg/kg body weight) prevented the diabetesinduced slowing of motor nerve conduction velocity and endoneurial blood flow. This therapy also significantly improved acetylcholine-mediated vasodilation in epineurial arterioles of the sciatic nerve compared to nontreated diabetic rats. Treating diabetic rats with 0.25%α-lipoic acid and fidarestat (3 mg/kg body weight) was equally or more effective in preventing vascular and neural dysfunction than was monotherapy of diabetic rats with higher doses ofα-lipoic acid or fidarestat. Treating diabetic rats with the combination of 0.25%α-lipoic acid and fidarestat (3 mg/kg body weight) significantly improved several markers of oxidative stress and increased the serum levels of bothα-lipoic acid and dihydrolipoic acid. These studies suggest that combination therapy consisting ofα-lipoic acid and fidarestat may be more efficacious in preventing diabetes-induced vascular and neural dysfunction in peripheral tissue compared to monotherapy, which requires higher doses to be equally effective. The effect of this combination therapy may in part be due to the increased production and/or level of dihydrolipoic acid.
Details
- Title: Subtitle
- Effect of Fidarestat andα-Lipoic Acid on Diabetes-Induced Epineurial Arteriole Vascular Dysfunction
- Creators
- M. A Yorek - Veterans Affairs Medical Center and Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52246, USAL. J Coppey - Veterans Affairs Medical Center and Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52246, USAJ. S Gellett - Veterans Affairs Medical Center and Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52246, USAE. P Davidson - Veterans Affairs Medical Center and Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52246, USAD. D Lund - Veterans Affairs Medical Center and Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52246, USA
- Resource Type
- Journal article
- Publication Details
- Experimental diabesity research, Vol.5(2), pp.123-135
- DOI
- 10.1080/15438600490277824
- PMID
- 15203883
- PMCID
- PMC2496880
- NLM abbreviation
- Exp Diabesity Res
- ISSN
- 1543-8600
- eISSN
- 1543-8619
- Language
- English
- Date published
- 2004
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984094605302771
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