Uptake, recycling, and antioxidant actions of α-lipoic acid in endothelial cells

Jones, Wright; Li, Xia; Qu, Zhi-chao; Perriott, Laureta M.; Whitesell, Richard R.; May, James M.

doi:10.1016/s0891-5849(02)00862-6

Cited by 192 publications

(151 citation statements)

References 42 publications

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“…ALA increased glutathione and decreased MDA, which can be explained by the ability of ALA to regenerate glutathione [9]. Furthermore, ALA has been reported to increase glutathione synthesis by increasing cellular uptake of the cysteine required for glutathione synthesis [21].…”

Section: Discussionmentioning

confidence: 97%

“…α-lipoic acid (ALA) has been identified as a powerful antioxidant by its ability to quench reactive oxygen species, decrease oxidative stress, recycle other antioxidants in the body including vitamins C and E and glutathione and protect against protein and lipid oxidation [8,9]. ALA has been considered to be safe and effective for treatment of symptomatic diabetic polyneuropathy [10,11].…”

Section: Introductionmentioning

confidence: 99%

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Alpha-Lipoic Acid Improves Subclinical Left Ventricular Dysfunction in Asymptomatic Patients with Type 1 Diabetes

Hegazy¹,

Tolba²,

Mostafa³

et al. 2013

Rev Diabet Stud

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■ Abstract BACKGROUND:Oxidative stress plays an important role in the development of diabetic cardiomyopathy. Alpha-lipoic acid (ALA) is a powerful antioxidant that may have a protective role in diabetic cardiac dysfunction. AIM: We investigated the possible beneficial effect of alpha-lipoic acid on diabetic left ventricular (LV) dysfunction in children and adolescents with asymptomatic type 1 diabetes (T1D). SUB-JECTS AND METHODS: Thirty T1D patients (aged 10-14) were randomized to receive insulin treatment (n = 15) or insulin plus alpha-lipoic acid 300 mg twice daily (n = 15) for four months. Age and sex matched healthy controls (n = 15) were also included. Patients were evaluated with conventional 2-dimensional echocardiographic examination (2D), pulsed tissue Doppler (PTD), and 2-dimensional longitudinal strain echocardiography (2DS) before and after therapy. Glutathione, malondialdhyde (MDA), nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), Fas ligand (Fas-L), matrix metalloproteinase 2 (MMP-2), and troponin-I were determined and correlated to echocardiographic parameters. RESULTS: Diabetic patients had significantly lower levels of glutathione and significantly higher MDA, NO, TNF-alpha, Fas-L, MMP-2, and troponin-I levels than control subjects. The expression of transforming growth factor beta (TGF-beta) mRNA in peripheral blood mononuclear cells was also increased in diabetic patients. Significant correlations of mitral e'/a' ratio and left ventricular global peak systolic strain with glutathione, MDA, NO, TNF-alpha, and Fas-L were observed in diabetic patients. Alpha-lipoic acid significantly increased glutathione level and significantly decreased MDA, NO, TNF-alpha, Fas-L, MMP-2, troponin-I levels, and TGF-beta gene expression. Moreover, alphalipoic acid significantly increased mitral e'/a' ratio and left ventricular global peak systolic strain in diabetic patients. CONCLUSION: These findings suggest that alpha-lipoic acid may have a role in preventing the development of diabetic cardiomyopathy in type 1 diabetes.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Alpha-Lipoic Acid Improves Subclinical Left Ventricular Dysfunction in Asymptomatic Patients with Type 1 Diabetes

Hegazy¹,

Tolba²,

Mostafa³

et al. 2013

Rev Diabet Stud

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“…A recent study by Jones et al [58], examined the uptake and antioxidant actions of ALP in endothelial cell cultures. Results indicated that with concentrations of ALP Ͼ0.5 mmol/L in cell culture, there is a concomitant fall in cellular GSH, NADPH, and NADH.…”

Section: Discussionmentioning

confidence: 99%

Effects of a medium chain triglyceride oil mixture and α-lipoic acid diet on body composition, antioxidant status, and plasma lipid levels in the Golden Syrian hamster

Wollin

Wang

Kubow

et al. 2004

The Journal of Nutritional Biochemistry

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The objective of this study was to examine the effects of the antioxidant ␣-lipoic acid (ALP) versus a medium chain triglyceride oil mixture (MCTo), which was designed to increase energy expenditure and to improve lipid profiles containing medium chain triglycerides, phytosterols, and omega-3 fatty acids in the form of flaxseed oil. A total of 48 hamsters were fed a) hypercholesterolemic (HC) control, b) HC MCTo, c) HC ALP, or d) HC MCTo/ALP diet for 4 weeks. No differences were observed on food intake, body weight, total body water, lean and fat mass, and tissue thiobarbituric acid reactive substances (TBARS). ALP alone had no effect on total cholesterol (TC); however, MCTo feeding increased TC with (P Ͻ 0.03) and without (P Ͻ 0.003) ALP when compared with control. ALP increased HDL levels compared with control (P Ͻ 0.04) and MCTo/ALP (P Ͻ 0.007) groups. MCTo, with (P Ͻ 0.0001) or without (P Ͻ 0.006) ALP, increased non-HDL cholesterol levels versus control. The non-HDL:HDL cholesterol ratio was decreased by ALP compared with MCTo (45%) and MCTo/ALP (68%) (P Ͻ 0.0001), a similar trend was seen when compared with the HC control (22%) group (P Ͻ 0.14). Triglyceride levels were not altered by any dietary treatment. Liver and heart tissue reduced glutathione (GSH) was increased (P Ͻ 0.05) by all three treatments when compared with control. Both tissues showed an increase (P Ͻ 0.05) in oxidized glutathione (GSSG) when fed ALP as compared with other treatments. Hamsters fed ALP had a lower (P Ͻ 0.05) GSH/GSSG ratio compared with other treatment groups. In conclusion, MCTo feeding does not elicit beneficial effects on circulating plasma lipids and measures of body composition. In addition, our results do not clearly support an improvement in oxidative status through supplementation of ALP. However, our results do support the existence of beneficial effects of ALP on circulating lipoprotein content in the hamster.

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“…BAPTA-AM and ODQ were dissolved in dimethyl sulfoxide and diluted to a final dimethyl sulfoxide concentration of 0.06%. PerkinElmer Life Sciences supplied the [carboxyl- 14 C]inulin (molecular weight range, 5000 -5500; 2 mCi/g).…”

Section: Methodsmentioning

confidence: 99%

“…EA.hy926 is an immortalized hybridoma line derived from HUVECs. They retain features of endothelial cells in culture, including a cobblestone appearance with formation of capillary-like tubes (12) and calcium-dependent endothelial nitric-oxide synthase activity (13,14). Cells were cultured at 37°C in humidified air containing 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

Intracellular Ascorbate Prevents Endothelial Barrier Permeabilization by Thrombin

Parker

May

2015

Journal of Biological Chemistry

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Uptake, recycling, and antioxidant actions of α-lipoic acid in endothelial cells

Cited by 192 publications

References 42 publications

Alpha-Lipoic Acid Improves Subclinical Left Ventricular Dysfunction in Asymptomatic Patients with Type 1 Diabetes

Alpha-Lipoic Acid Improves Subclinical Left Ventricular Dysfunction in Asymptomatic Patients with Type 1 Diabetes

Effects of a medium chain triglyceride oil mixture and α-lipoic acid diet on body composition, antioxidant status, and plasma lipid levels in the Golden Syrian hamster

Intracellular Ascorbate Prevents Endothelial Barrier Permeabilization by Thrombin

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