Further investigations of the role of acetylation in ...
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| Title | Further investigations of the role of acetylation in sulphonamide hypersensitivity reactions |
| Author(s) | C. Nuss, D. Grant, S. Spielberg, A. Cribb |
| Journal | Biomarkers |
| Date | 1996 |
| Volume | 1 |
| Issue | 4 |
| Start page | 267 |
| End page | 272 |
| Abstract | Sulphonamide hypersensitivity reactions are believed to be mediated through reactive intermediates derived from oxidation of the para-amino group to form sulphonamide hydroxylamines. Sulphamethoxazole hydroxylamine (SMX-HA) can be acetylated by N-acetyltransferase (NAT) enzymes to form an acetoxy metabolite (acetoxySMX). In the current studies, acetoxySMX was found to be not toxic over the concentration range of 0 to 500 mu M towards a human lymphoblastoid cell line (RPMI 1788) or a human hepatoma cell line (HepG2). Further, transient expression of NAT1 in COS-1 cells or stable transfection of NAT1 and NAT2 in HepG2 cells did not alter the toxicity of SMX-HA in vitro. The activity of NAT1 in isolated mononuclear leucocytes (a reflection of systemic NAT1 activity) determined with para-aminobenzoic acid as a substrate was not different between controls (n = 11) or patients with a known hypersensitivity reaction (n = 5) (4.1 +/- 1.2 nmol min(-1) mg(-1) vs 5.7 +/- 1.4 nmol min(-1) mg(-1)). Thus, acetoxySMX is unlikely to play a significant role in mediating SMX hypersensitivity reactions and a constitutive deficiency in NAT1 activity is not a common finding in patients susceptible to SMX hypersensitivity reactions. |
| ISSN | 1354-750X |
Using APA 6th Edition citation style.
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