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lipoic, lipoic acid, alpha lipoic, alpha-lipoic acid, antioxidant

Alpha-Lipoic Acid and HIV

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 Erlangen-Nurnberg.
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 School, Japan.
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.
Hernandez V.
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, Grune T.
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 patients.

Supplementation with antioxidant vitamins prevents oxidative modification of DNA in lymphocytes of HIV-infected patients.
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 abstracts from Pubmed