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Toxicity of Sulfonamide-Reactive Metabolites in HIV-Infected, HTLV-Infected, and Noninfected Cells

Rieder, Michael J.; Krause, Richard; Bird, Ingrid A.; Dekaban, Gregory A.
JAIDS Journal of Acquired Immune Deficiency Syndromes: February 1995
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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 μM 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.

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