Antioxidants and dipyridamole inhibit HIV-1 gp120-induced free radical-based oxidative damage to human monocytoid cells

Irene O. Foga, Avindra Nath, Brian B. Hasinoff, Jonathan D. Geiger

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Reactive oxygen species (ROS) may play an important role in HIV-1 pathogenesis and HIV-1 gp120-induced neurotoxicity. Our studies determined the extent to which gp120 increased ROS production in human monocytic U937 cells and the effectiveness of various agents, including dipyridamole (DPR), in blocking these responses. The thiobarbituric acid-reactive substances (TBARS) assay was used as a measure of recombinant gp120 (HIV-13B)-induced oxidative damage to U937 cells. As a control, TBARS production was measured using a hypoxanthine/xanthine superoxide generating system. There was gp120-induced oxidative damage in U937 cells with a concentration that produces 50% of maximal effect (apparent EC50 value) of 11 pM. Polyclonal antiserum to gp120 significantly (p < 0.05) inhibited gp120-induced oxidative damage. gp120-induced oxidative damage was significantly inhibited 81% (p < 0.01) by catalase/superoxide dismutase, 53% (p < 0.05) by (±)-α-tocopherol, 78% (p < 0.01) by desferrioxamine, and 82% (p < 0.01) by ethylene diamine tetraacetic acid (EDTA). These results indicate that gp120 is capable of promoting iron-based oxygen free radical damage to U937 cells. DPR potently (p < 0.05) inhibited both hypoxanthine/xanthine- and gp120-induced oxidative damage with concentrations that produce 50% inhibition (apparent IC50 values) of 1.3 μM for hypoxanthine/xanthine and 1.0 μM for gp120. Therapeutic intervention against ROS production may prevent HIV-1 neurotoxicity.

Original languageEnglish (US)
Pages (from-to)223-229
Number of pages7
JournalJournal of Acquired Immune Deficiency Syndromes and Human Retrovirology
Volume16
Issue number4
DOIs
StatePublished - Dec 1 1997

Keywords

  • Antioxidants
  • Dipyridamole
  • HIV-1
  • Iron
  • Monocytes
  • Reactive oxygen species
  • U937 cells
  • gp120

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Virology

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