Document Detail


Toxicity of sulfonamide-reactive metabolites in HIV-infected, HTLV-infected, and noninfected cells.
MedLine Citation:
PMID:  7834397     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
M J Rieder; R Krause; I A Bird; G A Dekaban
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association     Volume:  8     ISSN:  1077-9450     ISO Abbreviation:  J. Acquir. Immune Defic. Syndr. Hum. Retrovirol.     Publication Date:  1995 Feb 
Date Detail:
Created Date:  1995-03-01     Completed Date:  1995-03-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9501482     Medline TA:  J Acquir Immune Defic Syndr Hum Retrovirol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  134-40     Citation Subset:  IM; X    
Affiliation:
J. P. Robarts Research Institute, Department of Paediatrics, Western Ontario, London, Canada.
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MeSH Terms
Descriptor/Qualifier:
Adult
Cells, Cultured
Deltaretrovirus Infections / drug therapy*
Dose-Response Relationship, Drug
Drug Hypersensitivity / etiology
HIV Infections / drug therapy*
Humans
Models, Biological
Sulfamethoxazole / analogs & derivatives*,  toxicity
T-Lymphocytes / drug effects*,  virology
Toxicity Tests
Chemical
Reg. No./Substance:
114438-33-4/sulfamethoxazole hydroxylamine; 723-46-6/Sulfamethoxazole

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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