Alpha-lipoic acid is an effective inhibitor
of human immuno-deficiency virus (HIV-1) replication.
Baur A, Harrer T, Peukert M, Jahn G, Kalden JR, Fleckenstein B.
Institut fur Klinische und Molekulare Virologie der Universitat
Klin Wochenschr. 1991 Oct 2;69(15):722-4.
Alpha-lipoic acid, a naturally occurring disulfide-compound
that acts as a cellular coenzyme, inhibits replication of HIV-1
in cultured lymphoid T-cells. Alpha-lipoic acid was added 16 hours
after infection of the T-cell lines Jurkat, SupT1 and Molt-4 with
HTLV IIIB and HIV-1 Wal (a wild type HIV-1 isolate). We observed
a dose dependent inhibition of HIV-1-replication in CPE (Cytopathic
effect) formation, reverse transcriptase activity and plaque formation
on CD4-transformed HeLa-cells. An over 90% reduction of reverse
transcriptase activity could be achieved with 70 micrograms alpha-lipoic
acid/ml, a complete reduction of plaque-forming units at concentrations
of greater than or equal to 35 micrograms alpha-lipoic acid/ml.
An augmentation of the antiviral activity was seen by combination
of zidovudine and low dose of alpha-lipoic acid (7 micrograms/ml).
Trypan blue staining revealed no toxic effects of alpha-lipoic
acids on peripheral blood mono-nuclear cells and T-cell lines
even in concentrations of greater than or equal to 70 micrograms/ml.
Therefore, we propose the inclusion of alpha-lipoic acid into
chemotherapy trials in combination with zidovudine.
Alpha-lipoic acid blocks HIV-1 LTR-dependent
expression of hygromycin resistance in THP-1 stable transformants.
Merin JP, Matsuyama M, Kira T, Baba M, Okamoto T.
Department of Molecular Genetics, Nagoya City University Medical
FEBS Lett. 1996 Sep 23;394(1):9-13.
Gene expression of human immunodeficiency virus
(HIV) depends on a host cellular transcription factors including
nuclear factor-kappaB (NF-kappaB). The involvement of reactive
oxygen intermediates (ROI) has been implicated as intracellular
messengers in the inducible activation of NF-kappaB. In this study,
we compared the efficacy of two antioxidants, alpha-lipoic acid
(LA) and N-acetylcysteine (NAC), which are widely recognized NF-kappaB
inhibitors. Here, we demonstrate that LA has a more potent activity
in inhibiting NF-KappaB-mediated gene expression in THP-1 cells
that have been stably transfected with a plasmid bearing a hygromycin
B resistance gene under the control of HIV-1 long terminal repeat
(LTR) promoter. The spontaneous activation of NF-kappaB in this
cell culture system leads to expression of the hygromycin phosphotransferase
gene hence rendering the cells resistance to hygromycin B. In
this study, the effect of the test compounds against transcriptional
activity of HIV-1 LTR was evaluated based on the degree of cellular
toxicity due to the inhibitory activity on the expression of hygromycin
B resistance gene in the presence of hygromycin B. We also found
that 0.2 mM LA could cause 40% reduction in the HIV-1 expression
from the TNF-alpha-stimulated OM 10.1, a cell line latently infected
with HIV-1. On the other hand, 10 mM NAC was required to elicit
the same effect. Furthermore, the initiation of HIV-1 induction
by TNF-alpha was completely abolished by 1 mM LA. These findings
confirm the involvement of ROI in NF-kappaB-mediated HIV gene
expression as well as the efficacy of LA as a therapeutic regimen
for HIV infection and acquired immunodeficiency syndrome (AIDS).
Moreover, this study validates the applicability of our present
assay system which we primarily designed for the screening of
candidate drugs against HIV-1 gene expression.
Liver function and HIV-1 infection.
Direct AIDS Alternative Information Resources, New York, NY.
STEP Perspect. 1995 Summer;7(2):13-5.
AIDS: Persons with HIV may have previous or concurrent
liver impairment as a result of injection drug use, hepatitis,
alcohol abuse, and damage from medications. Additional stress
is placed on the liver by low-grade opportunistic infections and
hemophilia. It is especially important that persons with HIV care
for their liver to help this organ remain physiologically normal
during chronic and acute management of HIV infection. Although
modern pharmaceutical medicine does not provide liver tonics or
supportives, herbal medicines have been used to ease liver stress
for ages. Readily available liver protectants and their actual
mechanism of action, including thioctic acid, glycyrrhizin, and
Silybum marianum, are described.
Studies on lipoate effects on blood redox
state in human immunodeficiency virus infected patients.
Fuchs J, Schofer H, Milbradt R, Freisleben HJ, Buhl R, Siems W,
Department of Dermatology, University Hospital, Frankfurt/Main,
Fed. Rep. of Germany. Arzneimittelforschung. 1993 Dec;43(12):1359-62.
Several investigators have implicated that human immunodeficiency
virus (HIV) infected patients have a compromised antioxidant defense
system. Blood antioxidants are decreased and peroxidation products
of lipids and proteins are increased in the patients. This may
have pathophysiological implications, because antioxidants, such
as glutathione, and reactive oxidants are involved in the regulation
of the human immunodeficiency virus. Consequently it was suggested
that HIV infected patients may benefit from antioxidant supplementation
therapy. In a open and unblinded pilot study the short term effect
of the natural antioxidant lipoate (Thioctacid) on blood antioxidants
and peroxidation products was investigated in HIV positive patients
(CDC IV). In the majority of the patients, lipoate increased plasma
ascorbate (9 of 10 patients) total glutathione (7 of 7 patients),
total plasma thiol groups (8 of 9 patients); T helper lymphocytes
and T helper/suppressor cell ratio (6 of 10 patients), while the
lipid peroxidation products malondialdehyde (8 of 9 patients)
and 4-hydroxynonenal (7 of 9 patients) were decreased. The results
of this pilot study indicate that lipoate supplementation changes
the blood redox state of HIV infected patients. A prospective
and longitudinal therapy study is warranted to investigate the
long term effects of lipoate therapy on blood redox state, disease
progression and incidence of opportunistic infections in HIV infected
Supplementation with antioxidant vitamins
prevents oxidative modification of DNA in lymphocytes of HIV-infected
Jaruga P, Jaruga B, Gackowski D, Olczak A, Halota W, Pawlowska
M, Olinski R.
Department of Clinical Biochemistry, The Ludwik Rydygier Medical
University, Bydgoszcz, Poland.
Free Radic Biol Med. 2002 Mar 1;32(5):414-20.
There is evidence suggesting that patients infected with human
immunodeficiency virus (HIV) are under chronic oxidative stress.
In the present study, the level of oxidatively modified bases
in lymphocyte DNA and some other parameters of oxidative stress
were measured in HIV-infected patients (n = 30), as well as in
control groups (10 healthy volunteers and 15 HIV-seronegative
injected drug users). Additional experiments were conducted using
lymphocyte DNA samples from asymptomatic seropositive, HIV-infected
patients who were supplemented with antioxidant vitamins A, C,
and E or received placebo. Significant increases in the amount
of the modified DNA bases were observed in HIV-infected patients
when compared with the control group. The concentration of thiobarbituric
acid reactive substances (TBARS) was higher and activities of
antioxidant enzymes (superoxide dismutase and catalase) were lower
in the group of HIV-infected patients in comparison to the control
group. Vitamin supplementation resulted in the significant decrease
in the levels of all modified DNA bases when compared to the patients
who received placebo. The reduction of TBARS and the restoration
of the activity of the enzymes were also observed. Our data suggest
that people infected with HIV can benefit from treatment with
antioxidant vitamins. Scientific