Covalent binding of nitroso-sulfonamides to glutathione S-transferase in guinea pigs with delayed type hypersensitivity

Reiko Eyanagi, Akihisa Toda, Masumi Imoto, Hidemori Uchiyama, Yuji Ishii, Hiroaki Kuroki, Yukako Kuramoto, Shinji Soeda, Hiroshi Shimeno

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Drug induced allergies are believed to be induced by conjugates consisting of biological macromolecules and active metabolites. The present study investigated whether guinea pig glutathione S-transferase (gpGST), a protein that binds with sulfanilamide (SA) and sulfamethoxazole (SMX), could be detected in the liver cytosol fraction of guinea pigs that intraperitoneally received SA or SMX, and whether gpGST is a carrier protein. We synthesized three nitroso compounds, i.e., 4-nitroso-sulfanilamide (SA-NO), 4-nitrososulfamethoxazole (SMX-NO) and fluorescent-labeled nitroso compound (DNSBA-NO), and examined binding quantities of nitroso compounds to gpGST purified from untreated female guinea pigs. Furthermore, the concentrations of IgG in serum antibody for nitroso compounds were estimated using ELISA. When guinea pigs were sensitized using the three nitroso compounds, the dose dependent skin reactions were confirmed with each compound. In addition, sensitized guinea pigs using each nitroso compound showed positive skin reactions at an elicitation test performed using gpGST alone. The results confirmed synthesis of antibody against gpGST due to hapten sensitization. Therefore, when a nitroso compound binds with gpGST in the body of guinea pigs, nitroso-gpGST acts as a neoantigen, which induces synthesis of autoantibody. Thus, gpGST appears to be one of the carrier proteins that induce sulfa drug-induced allergies. Immunization of guinea pigs with active metabolite of drugs may give information for predicting the occurrence of delayed type hypersensitivity in human.

Original languageEnglish
Pages (from-to)694-700
Number of pages7
JournalInternational Immunopharmacology
Volume12
Issue number4
DOIs
Publication statusPublished - Apr 1 2012

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Sulfonamides
Delayed Hypersensitivity
Glutathione Transferase
Guinea Pigs
Nitroso Compounds
Sulfamethoxazole
Drug Hypersensitivity
Carrier Proteins
Skin
Antibodies
Haptens
Autoantibodies
Cytosol
Immunization

All Science Journal Classification (ASJC) codes

  • Immunology
  • Immunology and Allergy
  • Pharmacology

Cite this

Covalent binding of nitroso-sulfonamides to glutathione S-transferase in guinea pigs with delayed type hypersensitivity. / Eyanagi, Reiko; Toda, Akihisa; Imoto, Masumi; Uchiyama, Hidemori; Ishii, Yuji; Kuroki, Hiroaki; Kuramoto, Yukako; Soeda, Shinji; Shimeno, Hiroshi.

In: International Immunopharmacology, Vol. 12, No. 4, 01.04.2012, p. 694-700.

Research output: Contribution to journalArticle

Eyanagi, Reiko ; Toda, Akihisa ; Imoto, Masumi ; Uchiyama, Hidemori ; Ishii, Yuji ; Kuroki, Hiroaki ; Kuramoto, Yukako ; Soeda, Shinji ; Shimeno, Hiroshi. / Covalent binding of nitroso-sulfonamides to glutathione S-transferase in guinea pigs with delayed type hypersensitivity. In: International Immunopharmacology. 2012 ; Vol. 12, No. 4. pp. 694-700.
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