Alpha-lipoic acid as a biological antioxidant

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Abstract

α-Lipoic acid, which plays an essential role in mitochondrial dehydrogenase reactions, has recently gained considerable attention as an antioxidant. Lipoate, or its reduced form, dihydrolipoate, reacts with reactive oxygen species such as superoxide radicals, hydroxyl radicals, hypochlorous acid, peroxyl radicals, and singlet oxygen. It also protects membranes by interacting with vitamin C and glutathione, which may in turn recycle vitamin E. In addition to its antioxidant activities, dihydrolipoate may exert prooxidant actions through reduction of iron. α-Lipoic acid administration has been shown to be beneficial in a number of oxidative stress models such as ischemia-reperfusion injury, diabetes (both α-lipoic acid and dihydrolipoic acid exhibit hydrophobic binding to proteins such as albumin, which can prevent glycation reactions), cataract formation, HIV activation, neurodegeneration, and radiation injury. Furthermore, lipoate can function as a redox regulator of proteins such as myoglobin, prolactin, thioredoxin and NF-κB transcription factor. We review the properties of lipoate in terms of (1) reactions with reactive oxygen species; (2) interactions with other antioxidants; (3) beneficial effects in oxidative stress models or clinical conditions.

References (158)

  • SearlsR.L. et al.

    α-Ketoglutaric dehydrogenase. 8. Isolation and some properties of a flavoprotein component

    J. Biol. Chem.

    (1960)
  • BonomiF. et al.

    Synthesis and characterization of iron derivatives of dihydrolipoic acid and dihydrolipoamide

    Inorgan. Chim. Acta.

    (1992)
  • BonomiF. et al.

    Molecular aspects of the removal of ferritin-bound iron by DL-dihydrolipoate

    Biochim. Biophys. Acta.

    (1989)
  • ReedC.J. et al.

    Single-strand cleavage of DNA by Cu(II) and thiols: A powerful chemical DNA-cleaving system

    Bioch. Biophys. Res. Comm.

    (1989)
  • ScholichH. et al.

    Antioxidant activity of dihydrolipoate against microsomal lipid peroxidation and its dependence on α-tocopherol

    Biochim. Biophys. Acta.

    (1989)
  • KaganV.E. et al.

    Recycling of vitamin E in human low density lipoproteins

    J. Lipid Res.

    (1992)
  • ConstantinescuA. et al.

    Vitamin E recycling in human erythrocyte membranes

    J. Biol. Chem.

    (1993)
  • GotzM.E. et al.

    Effect of lipoic acid on redox state of coenzyme Q in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and diethyldithiocarbamate

    Eur. J. Pharmacol.

    (1994)
  • KaganV. et al.

    Antioxidant effects of ubiquinones in microsomes and mitochondria are mediated by tocopherol recycling

    Bioch. Biophys. Res. Comm.

    (1990)
  • ThomasJ.A. et al.

    Protein S-thiolation and dethiolation

    Meth. Enzymol.

    (1994)
  • RomeroF.J. et al.

    The reactivity of thiols and disulfides with different redox states of myoglobin: Redox and addition reactions and formation of thiyl radical intermediates

    J. Biol. Chem.

    (1992)
  • GleasonF.K. et al.

    Thioredoxin and related protein in procaryotes

    FEMS Microbiol. Rev.

    (1988)
  • HolmgrenA.

    Thioredoxin catalyzes the reduction of insulin disulfides by dithiothreitol and dihydrolipoamide

    J. Biol. Chem.

    (1979)
  • HolmgrenA.

    Thioredoxin and glutaredoxin systems

    J. Biol. Chem.

    (1989)
  • SpectorA. et al.

    Thioredoxin fragment 31–36 is reduced by dihydrolipoamide and reduces oxidized protein

    Biochem. Biophys. Res. Commun.

    (1988)
  • HayashiT. et al.

    Oxidoreductive regulation of nuclear factor kB: Involvement of a cellular reducing catalyst thioredoxin

    J. Biol. Chem.

    (1993)
  • BaeuerleP.A.

    The inducible transcription activator NF-kB: Regulation by distinct protein subunits

    Biochim. Biophys. Acta.

    (1991)
  • SuzukiY.J. et al.

    α-Lipoic acid is a potent inhibitor of NF-kB activation in human T cells

    Biochem. Biophys. Res. Commun.

    (1992)
  • MizunoM. et al.

    Effects of α-lipoic acid and dihydrolipoic acid on expression of the proto-oncogene c-fos

    Biochem. Biophys. Res. Comm.

    (1994)
  • BonserR.W. et al.

    Inhibition of phorbol ester stimulated superoxide production by 1-oleoyl-2-acetyl-sn-glycerol (OAG); fact or artefact?

    FEBS Letters

    (1986)
  • ShibanumaM. et al.

    Effects of the protein kinase C inhibitor H-7 and calmodulin antagonist W-7 on superoxide production in growing and resting human histiocytic leukemia cells (U937)

    Biochem. Biophys. Res. Comm.

    (1987)
  • HarrisonE.H. et al.

    The metabolism of dl-[1,6-14C] lipoic acid in the rat

    Arch. Biochem. Biophys.

    (1974)
  • PeinadoJ. et al.

    Hepatic lipoate uptake

    Arch. Biochem. Biophys.

    (1989)
  • SpenceJ.T. et al.

    Lipoic acid metabolism in the rat

    Arch. Biochem. Biophys.

    (1976)
  • WolffS.P. et al.

    Protein glycation and oxidative stress in diabetes mellitus and ageing

    Free Rad. Biol. Med.

    (1991)
  • FaustA. et al.

    Effect of lipoic acid on cyclophosphamide-induced diabetes and insulitis in nonobese diabetic mice

    Int. J. Immunopharmac.

    (1994)
  • HaugaardN. et al.

    Stimulation of glucose utilization by thioctic acid in rat diaphragm incubated in vitro

    Biochim. Biophys. Acta

    (1970)
  • SinghH.P.P. et al.

    Effect of D,L-alpha lipoic acid on the citrate concentration and phosphofructokinase activity of perfused hearts from normal and diabetic rats

    Biochem. Biophys. Res. Commun.

    (1970)
  • KawabataT. et al.

    Alpha-lipoate can protect against glycation of serum albumin, but not low density lipoprotein

    Biochem. Biophys. Res. Comms.

    (1994)
  • van BoekelM.A. et al.

    Glycation of human serum albumin: Inhibition by Diclofenac

    Biochim. Biophys. Acta.

    (1992)
  • ReedL.J. et al.

    Crystalline α-lipoic acid: a catalytic agent associated with pyruvate dehydrogenase

    Science

    (1951)
  • ReedL.J.

    The chemistry and function of lipoic acids

    Adv. Enzymol.

    (1957)
  • ReedL.J.

    Multienzyme complex

    Acc. Chem. Res.

    (1974)
  • RimmE.B. et al.

    Vitamin E consumption and the risk of coronary heart disease in men

    N. Engl. J. Med.

    (1993)
  • StampferM.J. et al.

    Vitamin E consumption and the risk of coronary disease in women

    N. Engl. J. Med.

    (1993)
  • HandelmanG.J. et al.

    α-Lipoic acid reduction by mammalian cells to the dithiol form and release into the culture medium

    Biochem. Pharmacol.

    (1994)
  • PoddaM. et al.

    Conversion of lipoic acid to dihydrolipoic acid in human keratinocytes

    Clin. Res.

    (1994)
  • SuzukiY.J. et al.

    Thioctic acid and dihydrolipoic acid are novel antioxidants which interact with reactive oxygen species

    Free Rad. Res. Comms.

    (1991)
  • ScottB.C. et al.

    Lipoic and dihydrolipoic acids as antioxidants: A critical evaluation

    Free Rad. Res.

    (1994)
  • StevensB. et al.

    The photoperoxidation of unsaturated organic molecules: IX. Lipoic acid inhibition of rubrene autoperoxidation

    Photochem. Photobiol.

    (1974)
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