Dihydrolipoic acid--a universal antioxidant
both in the membrane and in the aqueous phase. Reduction of peroxyl,
ascorbyl and chromanoxyl radicals.
Kagan VE, Shvedova A, Serbinova E, Khan S, Swanson C, Powell R,
Department of Molecular and Cell Biology, University of California,
Biochem Pharmacol. 1992 Oct 20;44(8):1637-49.
Thioctic (lipoic) acid is used as a therapeutic
agent in a variety of diseases in which enhanced free radical
peroxidation of membrane phospholipids has been shown to be a
characteristic feature. It was suggested that the antioxidant
properties of thioctic acid and its reduced form, dihydrolipoic
acid, are at least in part responsible for the therapeutic potential.
The reported results on the antioxidant efficiency of thioctic
and dihydrolipoic acids obtained in oxidation models with complex
multicomponent initiation systems are controversial. In the present
work we used relatively simple oxidation systems to study the
antioxidant effects of dihydrolipoic and thioctic acids based
on their interactions with: (1) peroxyl radicals which are essential
for the initiation of lipid peroxidation, (2) chromanoxyl radicals
of vitamin E, and (3) ascorbyl radicals of vitamin C, the two
major lipid- and water-soluble antioxidants, respectively. We
demonstrated that: (1) dihydrolipoic acid (but not thioctic acid)
was an efficient direct scavenger of peroxyl radicals generated
in the aqueous phase by the water-soluble azoinitiator 2,2'-azobis(2-amidinopropane)-dihydrochloride,
and in liposomes or in microsomal membranes by the lipid-soluble
azoinitiator 2,2'-azobis(2,4-dimethylvaleronitrile); (2) both
dihydrolipoic acid and thioctic acid did not interact directly
with chromanoxyl radicals of vitamin E (or its synthetic homologues)
generated in liposomes or in the membranes by three different
ways: UV-irradiation, peroxyl radicals of 2,2'-azobis(2,4-dimethylvaleronitrile),
or peroxyl radicals of linolenic acid formed by the lipoxygenase-catalyzed
oxidation; and (3) dihydrolipoic acid (but not thioctic acid)
reduced ascorbyl radicals (and dehydroascorbate) generated in
the course of ascorbate oxidation by chromanoxyl radicals. This
interaction resulted in ascorbate-mediated dihydrolipoic acid-dependent
reduction of the vitamin E chromanoxyl radicals, i.e. vitamin
E recycling. We conclude that dihydrolipoic acid may act as a
strong direct chain-breaking antioxidant and may enhance the antioxidant
potency of other antioxidants (ascorbate and vitamin E) in both
the aqueous and the hydrophobic membraneous phases.
Radioprotection of hematopoietic tissues in
mice by lipoic acid.
Ramakrishnan N, Wolfe WW, Catravas GN.
Office of the Chair of Science, Armed Forces Radiobiology Research
Institute, Bethesda, Maryland 20889-5145. Radiat Res. 1992 Jun;130(3):360-5.
Lipoic acid is a lipophilic antioxidant that participates in many
enzymatic reactions and is used clinically to treat mushroom poisoning
and metal toxicity. In this report the protective effect of lipoic
acid (oxidized form) against radiation injury to hematopoietic
tissues in mice was assessed by the endogenous and exogenous spleen
colony assays and survival (LD50/30) assay. Intraperitoneal administration
of lipoic acid at a nonlethal concentration of 200 mg/kg body
wt, 30 min before irradiation increased the LD50/30 from 8.67
to 10.93 Gy in male CD2F1 mice. Following a 9-Gy irradiation,
the yield of endogenous spleen colony-forming units in mice treated
with saline and lipoic acid was 0.75 +/- 0.5 and 8.9 +/- 1.6,
respectively. Using the exogenous spleen colony assay, lipoic
acid treatment increased the D0 from 0.81 +/- 0.01 to 1.09 +/-
0.01 Gy, yielding a dose modification factor of 1.34 +/- 0.01.
Dihydrolipoic acid (reduced form) has no radioprotective effect
in CD2F1 mice.
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. Scientific