Effects of α-lipoic acid on endothelial function in aged diabetic and high-fat fed rats

C M Sena,^1,2,* E Nunes,^1,2 T Louro,^1,2 T Proença,³ R Fernandes,⁴ M R Boarder,⁵ and R M Seiça^1,2

¹Institute of Physiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal

²Center for Neurosciences and Cell Biology of Coimbra, University of Coimbra, Coimbra, Portugal

³Laboratory of Neurochemistry, University Hospitals of Coimbra, Coimbra, Portugal

⁴IBILI, Faculty of Medicine, University of Coimbra, Coimbra, Portugal

⁵The Cell Signalling Laboratory, Leicester School of Pharmacy, De Montfort University, Leicester, UK

^*Author for correspondence: Email: csena@ci.uc.pt

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Received June 14, 2007; Revised July 24, 2007; Accepted August 21, 2007.

Copyright 2008, Nature Publishing Group

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From: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2267261/#bib12

Abstract

Background and purpose:

This study was conducted to investigate the effects of α-lipoic acid (α-LA) on endothelial function in diabetic and high-fat fed animal models and elucidate the potential mechanism underlying the benefits of α-LA.

Experimental approach:

Plasma metabolites reflecting glucose and lipid metabolism, endothelial function, urinary albumin excretion (UAE), plasma and aortic malondialdehyde (MDA) and urinary 8-hydroxydeoxyguanosine (8-OHdG) were assessed in non-diabetic controls (Wistar rats), untreated Goto-Kakizaki (GK) diabetic and high-fat fed GK rats (fed with atherogenic diet only, treated with α-LA and treated with vehicle, for 3 months). Vascular eNOS, nitrotyrosine, carbonyl groups and superoxide anion were also assessed in the different groups.

Key results:

α-LA and soybean oil significantly reduced both total and non-HDL serum cholesterol and triglycerides induced by atherogenic diet. MDA, carbonyl groups, vascular superoxide and 8-OHdG levels were higher in GK and high-fat fed GK groups and fully reversed with α-LA treatment. High-fat fed GK diabetic rats showed significantly reduced endothelial function and increased UAE, effects ameliorated with α-LA. This endothelial dysfunction was associated with decreased NO production, decreased expression of eNOS and increased vascular superoxide production and nitrotyrosine expression.

Conclusions and implications:

α-LA restores endothelial function and significantly improves systemic and local oxidative stress in high-fat fed GK diabetic rats. Improved endothelial function due to α-LA was at least partially attributed to recoupling of eNOS and increased NO bioavailability and represents a pharmacological approach to prevent major complications associated with type 2 diabetes.

Keywords: type 2 diabetes, high-fat diet, α-lipoic acid, oxidative stress, endothelial function, eNOS, nitric oxide, atherosclerosis