Antigenicity of sulfanilamide and its metabolites using fluorescent-labelled compounds

R. Eyanagi, A. Toda, Y. Ishii, H. Saito, S. Soeda, H. Shimeno, H. Shigematsu

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

In order to clarify the onset mechanisms of drug-induced allergies, three fluorescent-labelled compounds were synthesized by subjecting sulfanilamide (SA), a base compound for sulfonamides, and its active metabolites, i.e. sulfanilamide hydroxylamine and sulfanilamide nitroso, to dansylation using dansylchloride. In other words, 5-dimethylamino-N-(4-aminobenzyl)- naphthalenesulfonamide (DNS-4ABA), 5-dimethylamino-N-(4-hydroxylaminobenzyl)-1- naphthalenesulfonamide (DNS-4HABA) and 5-dimethylamino-N-(4-nitrosobenzyl)-1- naphthalenesulfonamide (DNS-4NSBA) were synthesized as model haptens. When analysed by HPLC, a conjugate of DNS-4HABA and glutathione (GSH) with nucleophilic amino acids had two peaks (P-1 and P-2). FAB-MS and 1H-NMR revealed that the DNS-4HABA-GSH conjugate consisted of sulphinamide and semimercaptal. The reactivity of GSH to DNS-4ABA, DNS-4HABA and DNS-4NSBA was quantified by HPLC using an oxidization system (horseradish peroxidase/H2O2). The results show that production of DNS-4NSBA-GSH-conjugate was four to eight times higher than that of DNS-4HABA-GSH conjugate, but that DNS-4ABA did not bind with GSH. Skin reactions were assessed using guinea pigs, and strong delayed erythema was seen with DNS-4NSBA, which bound most strongly with GSH, whereas weak delayed erythema was seen with DNS-4ABA, which did not bind with GSH. This suggests a correlation between GSH conjugate production and skin reactions. DNS-4HABA enzymatically bound with proteins in rat and guinea pig liver cytosol and microsomal fractions. The proteins that bound to DNS-4HABA were purified by HPLC and then subjected to N-terminal amino acid analysis. Ubiquitin (10 kDa) and fatty acid binding protein (30 kDa) were detected in the rat liver cytosol fraction; retinol-dehydrogenase (35 kDa) in the rat microsomal fraction; and glutathione-S-transferase B (mμ) (25 kDa) in the guinea pig liver cytosol fraction. When DNS-4HABA or DNS-4NSBA binds to proteins that play important roles in the body, unexpected adverse reactions may occur. Furthermore, by utilizing our technique using model compounds, it may be possible to identify the carrier proteins of various compounds, including pharmaceutical agents.

Original languageEnglish
Pages (from-to)911-925
Number of pages15
JournalXenobiotica
Volume35
Issue number9
DOIs
Publication statusPublished - Sep 1 2005

Fingerprint

Metabolites
Liver
Cytosol
Rats
Guinea Pigs
High Pressure Liquid Chromatography
Erythema
Skin
Allergies
Drug Hypersensitivity
Amino Acids
Fatty Acid-Binding Proteins
Hydroxylamine
Proteins
Haptens
Sulfonamides
Horseradish Peroxidase
Ubiquitin
Glutathione Transferase
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Health, Toxicology and Mutagenesis

Cite this

Eyanagi, R., Toda, A., Ishii, Y., Saito, H., Soeda, S., Shimeno, H., & Shigematsu, H. (2005). Antigenicity of sulfanilamide and its metabolites using fluorescent-labelled compounds. Xenobiotica, 35(9), 911-925. https://doi.org/10.1080/00498250500251533

Antigenicity of sulfanilamide and its metabolites using fluorescent-labelled compounds. / Eyanagi, R.; Toda, A.; Ishii, Y.; Saito, H.; Soeda, S.; Shimeno, H.; Shigematsu, H.

In: Xenobiotica, Vol. 35, No. 9, 01.09.2005, p. 911-925.

Research output: Contribution to journalArticle

Eyanagi, R, Toda, A, Ishii, Y, Saito, H, Soeda, S, Shimeno, H & Shigematsu, H 2005, 'Antigenicity of sulfanilamide and its metabolites using fluorescent-labelled compounds', Xenobiotica, vol. 35, no. 9, pp. 911-925. https://doi.org/10.1080/00498250500251533
Eyanagi, R. ; Toda, A. ; Ishii, Y. ; Saito, H. ; Soeda, S. ; Shimeno, H. ; Shigematsu, H. / Antigenicity of sulfanilamide and its metabolites using fluorescent-labelled compounds. In: Xenobiotica. 2005 ; Vol. 35, No. 9. pp. 911-925.
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