title: Irreversible photobinding of nitrofurantoin and of nitrofurfural to plasma proteins in vitro.
abstract: Allergic reactions form a serious problem in therapy with the urinary antiseptic nitrofurantoin (NFT). The formation of conjugates between NFT and plasma proteins is considered to be a first step in the development of such reactions. We investigated the possibility that UV-A irradiation of NFT in the presence of plasma proteins results in covalent binding. Binding to blood cell proteins was +/- 100X less. Efficient photobinding to albumin was demonstrated for NFT (up to 50 nmol mg-1 protein) and its photoproduct 5-nitrofurfural. Incubation of photodecomposition products from these two nitrofurans with plasma proteins also resulted in irreversible binding. Protein amino and, to a lesser extent, thiol groups proved to be targets for binding. Furthermore, upon photolysis both compounds induced a significant decrease in the iso-electric point of albumin. Photobinding, along with such alterations in the structure of plasma proteins, may well be able to trigger immunological responses when taking place in vivo. In this manner activation of nitrofurantoin by light may be a cause of allergic reactions by nitrofurantoin.
authors.affiliation: Center for Bio-Pharmaceutical Sciences, Division of Medicinal Chemistry, Leiden, The Netherlands.
authors.forename: R W
authors.initials: RW
authors.lastname: Busker
authors.forename: G M
authors.initials: GM
authors.lastname: Beijersbergen van Henegouwen
authors.forename: G J
authors.initials: GJ
authors.lastname: Vaassen
authors.forename: R F
authors.initials: RF
authors.lastname: Menke
mesh_terms: D000818:Animals; D001665:Binding Sites; D001798:Blood Proteins / Q000378:metabolism / Q000528:radiation effects*; D005662:Furaldehyde / Q000031:analogs & derivatives* / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology; D066298:In Vitro Techniques; D009582:Nitrofurantoin / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D010777:Photochemistry; D011817:Rabbits; D014466:Ultraviolet Rays
chemical_list: D001798:Blood Proteins; D009582:Nitrofurantoin; D005662:Furaldehyde; C052590:5-nitro-2-furaldehyde