Effect of Fidarestat and α-Lipoic Acid on Diabetes-Induced Epineurial Arteriole Vascular DysfunctionReport as inadecuate




Effect of Fidarestat and α-Lipoic Acid on Diabetes-Induced Epineurial Arteriole Vascular Dysfunction - Download this document for free, or read online. Document in PDF available to download.

Experimental Diabesity Research - Volume 5 2004, Issue 2, Pages 123-135

Veterans Affairs Medical Center and Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52246, USA

Received 4 August 2003; Accepted 3 October 2003

Copyright © 2004 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

In the present study, the authors examined whether treating streptozotocin-induced diabetic rats with the combination of α-lipoic acid and fidarestat, an aldose reductase inhibitor, can promote the formation of dihydrolipoic acid in diabetic animals and thereby enhance the efficacy of α-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 of α-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 both α-lipoic acid and dihydrolipoic acid. These studies suggest that combination therapy consisting of α-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.





Author: M. A. Yorek, L. J. Coppey, J. S. Gellett, E. P. Davidson, and D. D. Lund

Source: https://www.hindawi.com/



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