Thioctic Acid

Publication Title: 
Diabetologia

AIMS/HYPOTHESIS: Sirtuin 1 (SIRT1) is a longevity-associated protein, which regulates energy metabolism and lifespan in response to nutrient deprivation. It has been proposed to be a therapeutic target for obesity and metabolic syndrome. We investigated whether ?-lipoic acid (ALA) exerts a lipid-lowering effect through regulation of SIRT1 activation and production in C(2)C(12) myotubes.

Author(s): 
Chen, W.-L.
Kang, C.-H.
Wang, S.-G.
Lee, H.-M.
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

Glutathione (GSH) significantly declines in the aging rat liver. Because GSH levels are partly a reflection of its synthetic capacity, we measured the levels and activity of gamma-glutamylcysteine ligase (GCL), the rate-controlling enzyme in GSH synthesis. With age, both the catalytic (GCLC) and modulatory (GCLM) subunits of GCL decreased by 47% and 52%, respectively (P < 0.005). Concomitant with lower subunit levels, GCL activity also declined by 53% (P < 0.05).

Author(s): 
Suh, Jung H.
Shenvi, Swapna V.
Dixon, Brian M.
Liu, Honglei
Jaiswal, Anil K.
Liu, Rui-Ming
Hagen, Tory M.
Publication Title: 
Investigative Ophthalmology & Visual Science

PURPOSE: To determine whether (R)-alpha-lipoic acid (LA) protects cultured human fetal retinal pigment epithelial (hfRPE) cells against oxidative injury and identify the pathways that may mediate protection. METHODS: Cultured hfRPE cells were pretreated with various concentrations of LA for 14 to 16 hours followed by treatment with a chemical oxidant, tert-butylhydroperoxide (t-BuOOH; 0.8 mM, 3 hours). Reactive oxygen species (ROS) production and cell viability were measured using H(2)DCF and MTT assays, respectively.

Author(s): 
Voloboueva, Ludmila A.
Liu, Jiankang
Suh, Jung H.
Ames, Bruce N.
Miller, Sheldon S.
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was recently shown to negatively regulate LPS-induced acute inflammatory responses. We previously observed that the metabolic thiol antioxidant alpha-lipoic acid (LA) inhibits LPS-induced expression of cellular adhesion molecules and adherence of monocytes to human aortic endothelial cells. Here we investigated the mechanism by which LA attenuates LPS-induced monocyte activation in vitro and acute inflammatory responses in vivo.

Author(s): 
Zhang, Wei-Jian
Wei, Hao
Hagen, Tory
Frei, Balz
Publication Title: 
Journal of Alternative and Complementary Medicine (New York, N.Y.)

OBJECTIVE: To examine whether 3 months of lipoic acid (LA) supplementation improved walking tolerance and delayed claudication pain onset in peripheral arterial disease (PAD). DESIGN: Randomized, double-blind, controlled study. SETTING: General Clinical Research Center. SUBJECTS: Twenty-eight (28) participants (15 men, 13 women) with PAD (ankle brachial index range 0.9-0.4, mean age 73.2 +/- 1.6 years). INTERVENTION: LA (600 mg/day) or placebo for 3 months.

Author(s): 
Vincent, Heather K.
Bourguignon, Cheryl M.
Vincent, Kevin R.
Taylor, Ann G.
Publication Title: 
Clinical Biochemistry

OBJECTIVES: The reducing capacity of erythrocytes has been used clinically as to estimate resistance to oxidant stress. In this work we targeted the antioxidant capacity of pyridine nucleotide disulfide reductases of these cells by measuring their ability to reduce the disulfide alpha-lipoic acid. METHODS: Erythrocyte reduction of alpha-lipoic acid and related disulfides was measured as reduction of 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) outside the cells. RESULTS: Lipoic acid-dependent DTNB reduction by human erythrocytes required d-glucose and consumed NADPH, but not NADH.

Author(s): 
May, James M.
Qu, Zhi-chao
Nelson, Deanna J.
Publication Title: 
Circulation

BACKGROUND: Vascular inflammation and lipid deposition are prominent features of atherosclerotic lesion formation. We have shown previously that the dithiol compound alpha-lipoic acid (LA) exerts antiinflammatory effects by inhibiting tumor necrosis factor-alpha- and lipopolysaccharide-induced endothelial and monocyte activation in vitro and lipopolysaccharide-induced acute inflammatory responses in vivo.

Author(s): 
Zhang, Wei-Jian
Bird, Karyn E.
McMillen, Timothy S.
Leboeuf, Renée C.
Hagen, Tory M.
Frei, Balz
Publication Title: 
Brain, Behavior, and Immunity

We have initiated studies to evaluate the suitability of performing therapeutic conditioning trials in experimental autoimmune encephalomyelitis (EAE) mice treated with alpha lipoic acid (ALA). EAE was induced in SJL mice by active immunization with myelin antigen. Once daily subcutaneous injection of ALA served as the unconditional stimulus (US) administered with the conditional stimulus (CS) saccharin-flavored drinking water under a regimen of restricted water access.

Author(s): 
Jones, Richard E.
Moes, Nicole
Zwickey, Heather
Cunningham, Christopher L.
Gregory, William L.
Oken, Barry
Publication Title: 
British Journal of Pharmacology

BACKGROUND AND PURPOSE: The age-related decline in vasorelaxation is largely due to ceramide-induced induction of phosphatase 2A (PP2A), which limits nitric oxide synthase (eNOS) phosphorylation at stimulatory sites. We hypothesized that ceramide accumulation was from an age-related loss of endothelial glutathione (GSH) and subsequent activation of neutral sphingomyelinase (nSMase), an enzyme whose activity increases when GSH is limited. EXPERIMENTAL APPROACH: Old (30-32 mo) F344xBN rats were given (R)-alpha-lipoic acid (LA), an agent known to induce GSH synthesis.

Author(s): 
Smith, A. R.
Visioli, F.
Frei, B.
Hagen, T. M.
Publication Title: 
Journal of Alternative and Complementary Medicine (New York, N.Y.)

OBJECTIVES: To determine whether supplementation with alpha-lipoic acid (ALA), a glutathione-replenishing disulfide, modulates whole blood total glutathione (GSH + GSSG) levels and improves lymphocyte function in human immunodeficiency virus (HIV)-infected subjects with history of unresponsiveness to highly active antiretroviral treatment (HAART). DESIGN AND SETTING: Randomized, double-blinded, placebo-controlled trial conducted at two study sites: an eye clinic at a county hospital in San Jose and a research clinic in San Francisco, California.

Author(s): 
Jariwalla, Raxit J.
Lalezari, Jacob
Cenko, Diane
Mansour, Sam E.
Kumar, Abha
Gangapurkar, Bhakti
Nakamura, Daniel

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