|| Antioxidant adaptive response of human mononuclear
cells to UV-B: effect of lipoic acid.
Alvarez S, Boveris A.
Laboratory of Free Radical Biology, School of Pharmacy and Biochemistry,
University of Buenos Aires, Argentina.
J Photochem Photobiol B. 2000 Apr-May;55(2-3):113-9.
Supplementation of human mononuclear cells with
3 and 6 mM of lipoic acid produces an inhibition of the antioxidant
adaptive response triggered by treatment with UV-B light (0.30
W/m2 for 15 min). Supplementation with 1.5 mM of lipoic acid gives
no conclusive results. The adaptive response is characterized
by an increase in the activities of superoxide dismutase, catalase,
glutathione peroxidase and DT-diaphorase. Catalase (5.5 +/- 0.6
pmol/mg prot) increases its activity by up to 22 +/- 3 pmol/mg
prot, after irradiation with UV-B. Supplementation with 3 and
6 mM of lipoic acid completely inhibits the adaptive response.
The activities of the membrane-bound mitochondrial enzymes succinate
dehydrogenase and cytochrome oxidase do not increase after UV-B
exposure. Moreover, their activities are found to decrease and
the addition of lipoic acid does not prevent this effect. The
inhibition of the antioxidant response by lipoic acid in human
cells appears as indirect evidence of the existence of oxidative
stress in the development of this response. As lipoic acid behaves
as an effective antioxidant, it seems that its action decreases
the intracellular oxidative signals necessary to develop the adaptive
response in human mononuclear cells.
acid as a biological antioxidant.
Packer L, Witt EH, Tritschler HJ.
Department of Molecular & Cell Biology, University of California,
Berkeley 94720, USA.
Free Radic Biol Med. 1995 Aug;19(2):227-50.
alpha-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. alpha-Lipoic acid administration has been shown to be
beneficial in a number of oxidative stress models such as ischemia-reperfusion
injury, diabetes (both alpha-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-kappa B 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
The pharmacology of the antioxidant lipoic acid.
Biewenga GP, Haenen GR, Bast A.
Leiden/Amsterdam Center for Drug Research, Vrije Universiteit,
Department of Pharmacochemistry, The Netherlands.
1. Lipoic acid is an example of an existing drug
whose therapeutic effect has been related to its antioxidant activity.
2. Antioxidant activity is a relative concept: it depends on the
kind of oxidative stress and the kind of oxidizable substrate
(e.g., DNA, lipid, protein). 3. In vitro, the final antioxidant
activity of lipoic acid is determined by its concentration and
by its antioxidant properties. Four antioxidant properties of
lipoic acid have been studied: its metal chelating capacity, its
ability to scavenge reactive oxygen species (ROS), its ability
to regenerate endogenous antioxidants and its ability to repair
oxidative damage. 4. Dihydrolipoic acid (DHLA), formed by reduction
of lipoic acid, has more antioxidant properties than does lipoic
acid. Both DHLA and lipoic acid have metal-chelating capacity
and scavenge ROS, whereas only DHLA is able to regenerate endogenous
antioxidants and to repair oxidative damage. 5. As a metal chelator,
lipoic acid was shown to provide antioxidant activity by chelating
Fe2+ and Cu2+; DHLA can do so by chelating Cd2+. 6. As scavengers
of ROS, lipoic acid and DHLA display antioxidant activity in most
experiments, whereas, in particular cases, pro-oxidant activity
has been observed. However, lipoic acid can act as an antioxidant
against the pro-oxidant activity produced by DHLA. 7. DHLA has
the capacity to regenerate the endogenous antioxidants vitamin
E, vitamin C and glutathione. 8. DHLA can provide peptide methionine
sulfoxide reductase with reducing equivalents. This enhances the
repair of oxidatively damaged proteins such as alpha-1 antiprotease.
9. Through the lipoamide dehydrogenase-dependent reduction of
lipoic acid, the cell can draw on its NADH pool for antioxidant
activity additionally to its NADPH pool, which is usually consumed
during oxidative stress. 10. Within drug-related antioxidant pharmacology,
lipoic acid is a model compound that enhances understanding of
the mode of action of antioxidants in drug therapy.
Thioctic (lipoic) acid: a therapeutic metal-chelating
Ou P, Tritschler HJ, Wolff SP.
Department of Medicine, University College London Medical School,
Biochem Pharmacol. 1995 Jun 29;50(1):123-6.
Thioctic (alpha-lipoic) acid (TA) is a drug used
for the treatment of diabetic polyneuropathy in Germany. It has
been proposed that TA acts as an antioxidant and interferes with
the pathogenesis of diabetic polyneuropathy. We suggest that one
component of its antioxidant activity requiring study is the direct
transition metal-chelating activity of the drug. We found that
TA had a profound dose-dependent inhibitory effect upon Cu(2+)-catalysed
ascorbic acid oxidation (monitored by O2 uptake and spectrophotometrically
at 265 nm) and also increased the partition of Cu2+ into n-octanol
from an aqueous solution suggesting that TA forms a lipophilic
complex with Cu2+. TA also inhibited Cu(2+)-catalysed liposomal
peroxidation. Furthermore, TA inhibited intracellular H2O2 production
in erythrocytes challenged with ascorbate, a process thought to
be mediated by loosely chelated Cu2+ within the erythrocyte. These
data, taken together, suggest that prior intracellular reduction
of TA to dihydrolipoic acid is not an obligatory mechanism for
an antioxidant effect of the drug, which may also operate via
Cu(2+)-chelation. The R-enantiomer and racemic mixture of the
drug (alpha-TA) generally seemed more effective than the S-enantiomer
in these assays of metal chelation.
The antioxidant properties of thioctic acid:
characterization by cyclic voltammetry.
Chevion S, Hofmann M, Ziegler R, Chevion M, Nawroth PP.
Department of Internal Medicine, Heidelberg University, Germany.
Biochem Mol Biol Int. 1997 Feb;41(2):317-27.
Thioctic acid (TA) level and its antioxidant
capacity were monitored by cyclic voltammetry (CV), in solution
and in human plasma. A linear correlation between the anodic wave
current Ia at 900 mV and [TA] was obtained. This indicates that
TA, commonly found in human plasma, is an antioxidant component
characterized by a potential E1/2 = 900 mV and constitute, at
least in part, the second anodic wave of the CV tracing. When
plasma from diabetic patients was analyzed by CV, those patients
under treatment with TA showed higher Ia than others not taking
the drug. When the patients under treatment with TA were divided
into groups according to the severity of their nephropathy, or
according to the severity of their total complication count, Ia
levels representing TA were significantly higher in those patients
with more severe complications.