Glutathione precursor and antioxidant activities of N-acetylcysteine and oxothiazolidine carboxylate compared in in vitro studies of HIV replication

N-Acetyl-L-cysteine (NAC) and L-2-oxothiazolidine 4-carboxylate (OTC) are pro-GSH drugs that been proposed for AIDS therapy. In this article we compare the antiviral activities of these compounds in various in vitro HIV infection models. Although both compounds blocked cytokine induction of HIV in a...

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Bibliographic Details
Published inAIDS research and human retroviruses Vol. 10; no. 8; p. 961
Main Authors Raju, P A, Herzenberg, L A, Roederer, M
Format Journal Article
LanguageEnglish
Published United States 01.08.1994
Subjects
Acetylcysteine - pharmacology
Antimetabolites - pharmacology
Antioxidants - pharmacology
Antiviral Agents - pharmacology
Buthionine Sulfoximine
Cells, Cultured
Free Radical Scavengers - pharmacology
Gene Expression Regulation, Viral - drug effects
Genes, Reporter
Glutathione - biosynthesis
HIV Long Terminal Repeat - genetics
HIV-1 - drug effects
HIV-1 - physiology
Humans
Leukocytes, Mononuclear - virology
Methionine Sulfoximine - analogs & derivatives
Methionine Sulfoximine - pharmacology
Monocytes - virology
Prodrugs - pharmacology
Pyrrolidonecarboxylic Acid
Thiazoles - pharmacology
Thiazolidines
Tumor Necrosis Factor-alpha - pharmacology
Virus Replication - drug effects
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Summary:N-Acetyl-L-cysteine (NAC) and L-2-oxothiazolidine 4-carboxylate (OTC) are pro-GSH drugs that been proposed for AIDS therapy. In this article we compare the antiviral activities of these compounds in various in vitro HIV infection models. Although both compounds blocked cytokine induction of HIV in acute and chronic infection models, and in HIV-LTR reporter cell systems, NAC was far more effective than OTC, even at suboptimal doses. To test whether this difference is due to GSH conversion efficacies of these compounds, we measured GSH restoration by NAC or OTC in GSH-depleted peripheral blood mononuclear cells (PBMCs), using flow cytometry. In isolated PBMCs, NAC fully replenishes depleted intracellular GSH whereas OTC only minimally replenishes GSH. This ability to replenish GSH in vitro and its ability to scavenge free radicals directly explain why NAC has more potent antiviral activities in vitro.
ISSN:0889-2229
1931-8405
DOI:10.1089/aid.1994.10.961