Article date: March 2008
By: C M Sena, E Nunes, T Louro, T Proença, R Fernandes, M R Boarder, R M Seiça in Volume 153, Issue 5, pages 894-906
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.
DOI: 10.1038/sj.bjp.0707474
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