Lipoic acid. There is general agreement about the antioxidant
properties of a-lipoic acid. It scavenges hydroxyl
radicals, hypochlorous acid, and singlet oxygen.
It does not appear to scavenge hydrogen peroxide or
superoxide radical and probably does not scavenge peroxyl
radicals (Table 1). It may chelate transition
metals.
Two studies indicate that tr-lipoic acid is a potent
hydroxyl radical scavenger. In one, 12 hydroxyl radical
was generated by 2 mM HzO2 + 0.2 mM FeSO4. The
radical was detected by electron spin resonance (ESR)
using the spin-trapping agent 5,5-Dimethylpyrroline-
N-oxide (DMPO). 1 mM ot-lipoic acid completely
eliminated the DMPO-OH adduct signal. Another
study, 13 using a similar hydroxyl radical-generating
system (2.8 mM HzO2, 0.05 mM FeC13, 0.1 mM EDTA,
and 0.1 mM ascorbate) but a different assay for the
radical (deoxyribose degradation) also found ct-lipoic
acid to be a hydroxyl radical scavenger. In this study,
a rate constant of 4.7 × 101° M-is -~ was calculated;
this is an essentially diffusion-limited reaction rate.
Hence, ot-lipoic acid appears to be a highly effective
scavenger of hydroxyl radical.
There is similar agreement about the ability of otlipoic
acid to scavenge hypochlorous acid. Haenen and
Bast 14 and Scott et al.13 both found that 50 #M t~-lipoic
acid almost completely abolished the inactivation of
a 1-antiproteinase by 50/zM HOC1. This is in contrast
to glutathione, whose reduced form is a potent scavenger
of HOCI, comparable to ct-lipoic acid, but whose
oxidized form is almost completely ineffective. ~4 The
authors of this study speculate that the greater reactivity
of c~-lipoic acid compared to oxidized glutathione
may be due to the somewhat strained conformation of
the 5-membered ring in the intramolecular disulfide
form of a-lipoic acid; there is no such strain on the
intermolecular disulfide of glutathione disulfide, perhaps
explaining its lack of reactivity in this system.
c~-Lipoic acid has been reported to scavenge singlet
oxygen in at least four different systems. Two early
studies showed that a-lipoic acid reacted with singlet
oxygen generated by rubrene autooxidation 15 or by
photosensitized oxidation of methylene16; these
experiments were carried out in organic solvents. Later
studies conducted under more physiological conditions
also indicate that cz-lipoic acid is an effective scavenger
of singlet oxygen. Kaiser et al. 17 generated singlet
oxygen by thermolysis of endoperoxide and detected
it by chemiluminescence; in this system tz-lipoic acid
reacted with singlet oxygen with a rate constant of
1.38 × 108 M-Is -1. In experiments in which singlet
oxygen was generated by thermolysis of endoperoxide
and detected by single strand DNA breaks, c~-lipoic
acid was confirmed to be a scavenger of singlet
oxygen