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


METHODS
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 alpha-LA and treated with vehicle, for 3 months). Vascular eNOS, nitrotyrosine, carbonyl groups and superoxide anion were also assessed in the different groups.


RESULTS
alpha-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 alpha-LA treatment. High-fat fed GK diabetic rats showed significantly reduced endothelial function and increased UAE, effects ameliorated with alpha-LA. This endothelial dysfunction was associated with decreased NO production, decreased expression of eNOS and increased vascular superoxide production and nitrotyrosine expression.


CONCLUSIONS
alpha-LA restores endothelial function and significantly improves systemic and local oxidative stress in high-fat fed GK diabetic rats. Improved endothelial function due to alpha-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.
Sena
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CM
Institute of Physiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. csena@ci.uc.pt
Nunes
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Louro
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Fernandes
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Boarder
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Seiça
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D000375:Aging; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004041:Dietary Fats; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013024:Soybean Oil / Q000737:chemistry; D008063:Thioctic Acid / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
D000975:Antioxidants; D004041:Dietary Fats; D014280:Triglycerides; D009569:Nitric Oxide; D008063:Thioctic Acid; D013024:Soybean Oil; D002784:Cholesterol; D052250:Nitric Oxide Synthase Type III