of ot-lipoic acid on copper have recently been extended
to oxidation situations, a-Lipoic acid was effective in
preventing Cu2+-catalyzed ascorbic acid oxidation, increased
the partitioning of Cu 2÷ into n-octanol from
aqueous solution, and inhibited Cu2÷-catalyzed liposomal
peroxidation. 24 These observations indicate that alipoic
acid is a copper chelator.
In summary, a-lipoic acid scavenges hydroxyl radicals,
HOCI, and singlet oxygen, but is ineffective
against hydrogen peroxide and superoxide radical. It
chelates iron, copper, and other transition metals. Further
work is required to determine whether a-lipoic
acid is effective against peroxyl radicals.
Dihydrolipoic acid.Dihydrolipoic acid. With a redox
potential of -0.32 V (ref. 25) for the DHLA/a-lipoic
acid redox couple, dihydrolipoic acid is a potent reductant;
for comparison, the redox potential of the GSH/
GSSG couple is -0.24 V (ref. 26)-DHLA will reduce
GSSG to GSH, but GSH is incapable of reducing ctlipoic
acid to DHLA. 27
Like a-lipoic acid, DHLA is a potent antioxidant,
although there is more uncertainty as to its effects
(Table 2). There is agreement that DHLA scavenges
hypochlorous acid and peroxyl radicals and probably
scavenges hydroxyl radicals. It does not appear to react
with hydrogen peroxide or with singlet oxygen. However,
there is disagreement among studies as to whether
DHLA also is capable of scavenging superoxide radical
and whether it acts as an antioxidant or a prooxidant
in its interactions with iron ion.
In the systems in which a-lipoic acid was tested for
reaction with hypochlorous ion, DHLA was also found
to be effective, with about the same scavenging
ability. 14
DHLA is an effective peroxyl radical scavenger in
several different systems. Kagan et al. 9 used AAPH or
AMVN to generate peroxyl radicals in aqueous or lipid
systems, as described for a-lipoic acid, but, unlike otlipoic
acid, DHLA was found to scavenge peroxyl radicals
in these systems. It was also found to scavenge
peroxyl radicals generated by AMVN in liposomes and
detected by fluorescence decay of parinaric acid, 28 and
CC1302 radicals generated in aqueous solution as described
for a-lipoic acid13; in the latter system a rate
constant of 2.7 × 10 7 M-is -1 was calculated.
DHLA has been shown to have both antioxidant ~2
and prooxidant t3 effects in systems in which hydroxyl
radical was generated; however, the prooxidant effects,
if real, are probably due to DHLA's effects on iron
(see below). Both groups used iron salts and hydrogen