α-Lipoic Acid Prevents the Increase in Atherosclerosis Induced by Diabetes in Apolipoprotein E–Deficient Mice Fed High-Fat/Low-Cholesterol Diet

Yi, Xin; Maeda, Nobuyo

doi:10.2337/db06-0251

Cited by 105 publications

(64 citation statements)

References 49 publications

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“…It does so by activating the enzyme transketolase. α-Lipoic acid, a potent antioxidant, has also been reported to reduce diabetic microvascular and macrovascular complications in animal models [4,5]. To determine whether benfotiamine in combination with α-lipoic acid would normalise markers of reactive oxygen species-induced pathways of complications in humans, we performed a pilot study in participants with type 1 diabetes using one daily dose of benfotiamine in combination with α-lipoic acid.…”

Section: Introductionmentioning

confidence: 99%

Oral benfotiamine plus α-lipoic acid normalises complication-causing pathways in type 1 diabetes

Edelstein

Brownlee

2008

Diabetologia

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Aims/hypothesis We determined whether fixed doses of benfotiamine in combination with slow-release α-lipoic acid normalise markers of reactive oxygen species-induced pathways of complications in humans. Methods Male participants with and without type 1 diabetes were studied in the General Clinical Research Centre of the Albert Einstein College of Medicine. Glycaemic status was assessed by measuring baseline values of three different indicators of hyperglycaemia. Intracellular AGE formation, hexosamine pathway activity and prostacyclin synthase activity were measured initially, and after 2 and 4 weeks of treatment. Results In the nine participants with type 1 diabetes, treatment had no effect on any of the three indicators used to assess hyperglycaemia. However, treatment with benfotiamine plus α-lipoic acid completely normalised increased AGE formation, reduced increased monocyte hexosaminemodified proteins by 40% and normalised the 70% decrease in prostacyclin synthase activity from 1,709±586 pg/ml 6-keto-prostaglandin F 1α to 4,696±533 pg/ml. Conclusions/interpretation These results show that the previously demonstrated beneficial effects of these agents on complication-causing pathways in rodent models of diabetic complications also occur in humans with type 1 diabetes.Trial registration: NCT00703989

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Section: Introductionmentioning

confidence: 99%

Oral benfotiamine plus α-lipoic acid normalises complication-causing pathways in type 1 diabetes

Edelstein

Brownlee

2008

Diabetologia

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“…␣-Lipoic acid is an important mitochondrial antioxidant, and supplementation was shown to decrease atherosclerosis in hyperlipidemic, diabetic mice (2036). Heterozygous deficiency of lipoic acid synthase in diabetic mice resulted in a 48% increase in atherosclerosis extent (1111).…”

Section: Consequences Of Ros Overproduction: Genetic Damagementioning

confidence: 99%

Molecular Biology of Atherosclerosis

Hopkins

2013

Physiological Reviews

382

344

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At least 468 individual genes have been manipulated by molecular methods to study their effects on the initiation, promotion, and progression of atherosclerosis. Most clinicians and many investigators, even in related disciplines, find many of these genes and the related pathways entirely foreign. Medical schools generally do not attempt to incorporate the relevant molecular biology into their curriculum. A number of key signaling pathways are highly relevant to atherogenesis and are presented to provide a context for the gene manipulations summarized herein. The pathways include the following: the insulin receptor (and other receptor tyrosine kinases); Ras and MAPK activation; TNF-␣ and related family members leading to activation of NF-B; effects of reactive oxygen species (ROS) on signaling; endothelial adaptations to flow including G protein-coupled receptor (GPCR) and integrin-related signaling; activation of endothelial and other cells by modified lipoproteins; purinergic signaling; control of leukocyte adhesion to endothelium, migration, and further activation; foam cell formation; and macrophage and vascular smooth muscle cell signaling related to proliferation, efferocytosis, and apoptosis. This review is intended primarily as an introduction to these key signaling pathways. They have become the focus of modern atherosclerosis research and will undoubtedly provide a rich resource for future innovation toward intervention and prevention of the number one cause of death in the modern world.

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“…Further, DHLA has shown capability in regenerating reduced levels of exogeneous antioxidants such as tocopherols and vitamin C [Packer et al, 1995 [Kim et al, 2004]. In a study with LA supplementation for 20 weeks, it has been shown to prevent the increase of plasma total cholesterol and atherosclerotic lesions induced by diabetes in apolipoprotein E-deficient mice fed with high fat-low cholesterol diet [Yi & Maeda, 2006]. It has been further demonstrated that LA reduced atherosclerotic plaques in the abdominal aorta in hyperlipidemic rabbits with established atherosclerosis [Ying et al, 2010].…”

Section: Introductionmentioning

confidence: 99%

Phytosterol and α-Lipoic Acid Conjugates: Synthesis, Free Radical Scavenging Capacity and RP-LC-MS-APCI Analysis

Madawala¹,

Andersson²,

Jastrebova³

et al. 2012

Pol. J. Food Nutr. Sci.

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Plant sterols (PS) are bioactive compounds effective in reducing plasma cholesterol. Fatty acid esters of PS have improved solubility and blending properties when utilized in various food products. Naturally occurring α-lipoic acid (LA) and its reduced form dihydrolipoic acid (DHLA) are known for their antioxidant activity. In addition, they have shown an array of health benefi cial properties against obesity, diabetes, cancer, cardiovascular and infl ammatory diseases etc. Different LA conjugates have been reported to have increased bioactivity compared to the parent compounds. The objective of this study was to synthesize PS esters of LA (PSLA) and DHLA (PSDHLA) in order to increase their cholesterol lowering effect and reducing the risk of atherosclerosis with additional health benefi ts e.g. against oxidative stress.Synthesis of PSLA and PSDHLA was performed with a pure PS mixture of β-sitosterol, stigmasterol, campesterol and brassicasterol. The free radical scavenging capacity of the conjugates was assessed by the DPPH method. Remaining percentage of DPPH free radicals was measured at the steady state for different concentrations of PSLA and PSDHLA. High free radical scavenging capacity was observed for PSDHLA compared with PSLA. Effi cient concentration EC 50 as a molar ratio for PSDHLA was 0.43. The derivatives were analyzed by RP-HPLC-MS-APCI. The order of the elution times of the compounds observed in HPLC-MS analysis was PS< PSDHLA< PSLA. Baseline separation was not achieved between campesterol and stigmasterol and their derivatives. These compounds could be identifi ed by their characteristic fragment ions from the mass spectral data.

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α-Lipoic Acid Prevents the Increase in Atherosclerosis Induced by Diabetes in Apolipoprotein E–Deficient Mice Fed High-Fat/Low-Cholesterol Diet

Cited by 105 publications

References 49 publications

Oral benfotiamine plus α-lipoic acid normalises complication-causing pathways in type 1 diabetes

Oral benfotiamine plus α-lipoic acid normalises complication-causing pathways in type 1 diabetes

Molecular Biology of Atherosclerosis

Phytosterol and α-Lipoic Acid Conjugates: Synthesis, Free Radical Scavenging Capacity and RP-LC-MS-APCI Analysis

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