Document 0191
 DOCN  M9550191
 TI    Toxicity of sulfonamide-reactive metabolites in HIV-infected,
       HTLV-infected, and noninfected cells.
 DT    9505
 AU    Rieder MJ; Krause R; Bird IA; Dekaban GA; J. P. Robarts Research
       Institute, Department of Paediatrics,; Western Ontario, London, Canada.
 SO    J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Feb 1;8(2):134-40.
       Unique Identifier : AIDSLINE MED/95135991
 AB    It has been suggested that the high rates of adverse reactions to
       sulfonamides among patients with AIDS may be related to an increased
       sensitivity to reactive drug metabolites among HIV-infected cells. To
       study this hypothesis, we investigated the toxicity of the hydroxylamine
       of sulfamethoxazole in HIV-infected and noninfected MOLT-3 cultured
       human T-lymphoblasts. Toxicity was assessed by trypan blue dye
       exclusion. The hydroxylamine of sulfamethoxazole produced
       concentration-dependent toxicity in HIV-infected cells, with marked
       toxicity seen when HIV-infected cells were incubated with 400 microM of
       the hydroxylamine (82 +/- 8%); this was significantly greater than the
       toxicity seen among noninfected cells (p < 0.01). There was no
       concentration-dependent toxicity seen among noninfected cells or in
       cells infected with HTLV-I, suggesting that the concentration-dependent
       toxicity seen was specifically related to HIV infection. HIV-infected
       cells had significantly lower glutathione concentration than did
       noninfected cells (p < 0.05). Incubation with the hydroxylamine of
       sulfamethoxazole produced a concentration-dependent decline in
       glutathione content that was similar in infected and non-infected cells.
       Co-incubation with glutathione or N-acetylcysteine significantly reduced
       the toxicity of hydroxylamine of sulfamethoxazole in HIV-infected cells
       (p < 0.05). Our data supports the role of reactive sulfonamide
       metabolites in the pathogenesis of adverse reactions to sulfonamides
       among patients with AIDS.
 DE    Adult  Cells, Cultured  Comparative Study  Dose-Response Relationship,
       Drug  Drug Hypersensitivity/ETIOLOGY  Human  HIV Infections/*DRUG
       THERAPY  HTLV-BLV Infections/*DRUG THERAPY  Models, Biological
       Sulfamethoxazole/*ANALOGS & DERIVATIVES/TOXICITY  Support, Non-U.S.
       Gov't  T-Lymphocytes/*DRUG EFFECTS/VIROLOGY  Toxicity Tests  JOURNAL
       ARTICLE

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