BACKGROUND AND PURPOSE: 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. 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 alpha-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: 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 AND IMPLICATIONS: 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.
BACKGROUND AND PURPOSE: 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. 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 alpha-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: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 diabeticrats 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 AND IMPLICATIONS: alpha-LA restores endothelial function and significantly improves systemic and local oxidative stress in high-fat fed GK diabeticrats. 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.
Authors: U Hink; H Li; H Mollnau; M Oelze; E Matheis; M Hartmann; M Skatchkov; F Thaiss; R A Stahl; A Warnholtz; T Meinertz; K Griendling; D G Harrison; U Forstermann; T Munzel Journal: Circ Res Date: 2001-02-02 Impact factor: 17.367
Authors: Tauqir Y Goraya; Cynthia L Leibson; Pasquale J Palumbo; Susan A Weston; Jill M Killian; Eric A Pfeifer; Steven J Jacobsen; Robert L Frye; Véronique L Roger Journal: J Am Coll Cardiol Date: 2002-09-04 Impact factor: 24.094
Authors: Mehmet Erşahin; Hale Z Toklu; Sule Cetinel; Meral Yüksel; Can Erzik; M Zafer Berkman; Berrak C Yeğen; Göksel Sener Journal: Neurochem Res Date: 2009-10-13 Impact factor: 3.996