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https://hdl.handle.net/10316/12654
Title: | Effects of alpha-lipoic acid on endothelial function in aged diabetic and high-fat fed rats | Authors: | Sena, C. M. Nunes, E. Louro, T. Proença, T. Fernandes, R. 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: | https://hdl.handle.net/10316/12654 | ISSN: | 0007-1188 | DOI: | 10.1038/sj.bjp.0707474 | Rights: | openAccess |
Appears in Collections: | FMUC Medicina - Artigos em Revistas Internacionais |
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Effects of α-lipoic acid on endothelial function.pdf | 423.28 kB | Adobe PDF | View/Open |
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