|Title:||Effects of alpha-lipoic acid on endothelial function in aged diabetic and high-fat fed rats||Authors:||Sena, C. M.
Boarder, M. R.
Seiça, R. M.
|Keywords:||Type 2 diabetes;High-fat diet;α-lipoic acid;Oxidative stress;Endothelial function;eNOS;Nitric oxide;Atherosclerosis||Issue Date:||Mar-2008||Publisher:||Nature Publishing Group||Citation:||British Journal of Pharmacology. 153:5 (2008) 894-906||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||URI:||http://hdl.handle.net/10316/12654||ISSN:||0007-1188||Rights:||openAccess|
|Appears in Collections:||FMUC Medicina - Artigos em Revistas Internacionais|
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