Dihydrolipoic acid—a universal antioxidant both in the membrane and in the aqueous phase

Kagan, Valerian E.; Shvedova, Anna A.; Serbinova, E. A.; Khan, Shabi; Swanson, Chris J.; Powell, Richard E.; Packer, Lester

doi:10.1016/0006-2952(92)90482-x

Cited by 338 publications

(142 citation statements)

References 40 publications

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“…5). The bio-activity of LA was attributed both to its ability to directly react with various reactive oxygen species, as well as to its ability to interfere with oxidation processes in the lipid and in the aqueous cellular compartments [11,12]. As discussed above, the second possibility is more likely in this system in light of the requirement of at least 2-h incubation with LA before exposure to glucose oxidase, as well as the lack of effect of LA when present only during glucose oxidase treatment (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Lipoic acid protects against oxidative stress induced impairment in insulin stimulation of protein kinase B and glucose transport in 3T3-L1 adipocytes

et al. 1999

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Oxidative stress has been recently implicated in the pathogenesis of various diseases. Consequently, the potential therapeutic or preventive effects of antioxidative agents has been raised [1]. Both poorly controlled Type I (insulin-dependent) diabetes mellitus as well as Type II (non-insulin-dependent) diabetes mellitus are characterized by reduced capacity of peripheral tissues (i. e. skeletal muscle and adipose tissue) to respond to the metabolic effects of insulin. The causes and cellular mechanisms responsible for this abnormality are still not fully understood despite intense investigative effort. Several lines of evidence suggest that increased oxidative stress occurs in diabetes and could have a role in the development or deterioration of peripheral insulin resistance. These Diabetologia (1999) Abstract Aims/hypothesis. Oxidative stress has been shown to impair insulin-stimulated glucose transporter 4 translocation in 3T3-L1 adipocytes. This study explores the potential of the antioxidant lipoic acid to protect the cells against the induction of insulin resistance when given before exposure to oxidative stress. Methods. 3T3-LI were exposed for 16 h to lipoic acid after which cells were exposed for 2 h to continuous production of H 2 O 2 by adding glucose oxidase to the culture medium. Results. These conditions resulted in a 50±70 % reduction in insulin-stimulated glucose transport activity associated with a decrease in reduced glutathione content from 37.4 ± 3.1 to 26.4 ± 4.9 nmol/mg protein, (p < 0.005). Lipoic acid pretreatment increased insulin-stimulated glucose transport following oxidative stress, reaching 84.8 ± 4.4 % of the control, associated with an increase in reduced glutathione content. Oxidation impaired the 4.89 ± 0.36-fold insulin-stimulated increase in glucose transporter 4 content in plasma membrane lawns of control cells. Lipoic acid pretreatment was, however, associated with preserved insulin-induced glucose transporter 4 translocation in cells exposed to oxidation, yielding 80 % of its content in controls. Although tyrosine phosphorylation patterns were not affected by lipoic acid pretreatment, insulin-stimulated protein kinase B/Akt serine 473 phosphorylation and activity were considerably impaired by oxidation but protected by lipoic acid pretreatment. A protective effect was not observed with either troglitazone, its isolated vitamin E moiety, or with vitamin C. Conclusion/interpretation. This study shows the ability of lipoic acid to provide partial protection against the impaired insulin-stimulated glucose transporter 4 translocation and protein kinase B/Akt activation induced by oxidative stress, potentially by its capacity to maintain intracellular redox state. [Diabetologia (1999) 42: 949±957]

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Section: Discussionmentioning

confidence: 99%

“…It is both lipid and water soluble [12], has a potent antioxidative capacity in a wide variety of experimental systems and is a cofactor of key regulatory enzymes including the pyruvate dehydrogenase complex [10]. Recent studies showed that LA exhibits metabolic effects on glucose transport and utilization.…”

mentioning

confidence: 99%

Lipoic acid protects against oxidative stress induced impairment in insulin stimulation of protein kinase B and glucose transport in 3T3-L1 adipocytes

et al. 1999

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“…2). Thus, antioxidant effects of ALA or its derivates occur both in the hydrophilic phase and in the hydrophobic membrane portion [18][19][20]. Lipoic acid is synthesized in the body in very small amounts and is covalently bound to the E2 enzyme subunit of the four different alpha-keto acid dehydrogenase complexes in mitochondria.…”

Section: Alpha-lipoic Acid (Lipoate)mentioning

confidence: 99%

“…The antioxidant capacity of ALA is located in the thiol group, which reacts directly with oxidant radicals. Lipoate also contributes in other antioxidant systems by enhancing the effects of SOD [22], coenzyme Q10 and glutathione [11,23], and by regenerating other antioxidants such as vitamins C and E [18]. Furthermore, ALA plays an important role in cellular and mitochondrial membranes by modifying the metabolism of ketoacids and modulating mitochondrial ratios of NADH/NAD+ and NADHP/ NADP+ [19,20].…”

Section: Alpha-lipoic Acid (Lipoate)mentioning

confidence: 99%

Therapeutic perspectives on the combination of α-lipoic acid and vitamin E

González-Pérez

González-Castañeda

2006

Nutrition Research

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Alpha-lipoic acid and vitamin E have synergistic effects, as determined in models of oxidant radical lesions. This review summarizes recent findings showing that the combination of alpha-lipoic acid plus vitamin E has beneficial effects in reducing oxidative damage in ischemic or other oxidationrelated pathological events. Both antioxidants are common in the normal human diet and side effects are very rare. Therefore, alpha-lipoic acid and vitamin E can counteract oxidative processes and could have an important role in clinical medicine.

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“…a-Lipoic acid can interfere with lipid peroxidation by competing for free transition metals as a chelator (Muller & Menzel, 1990) and by scavenging hydroxyl radicals (Suzuki et al, 1991). On the other hand, DHLA can scavenge peroxyl radicals (Kagan et al, 1992). Both compounds are capable of scavenging superoxide radicals (Suzuki et al, 1991) and are integrated in the antioxidant network (Figure 3).…”

Section: Thiol-based Antioxidantsmentioning

confidence: 99%