title: Mechanistic Studies on the Photoallergy Mediated by Fenofibric Acid: Photoreactivity with Serum Albumins.
abstract: The photoreactivity of fenofibric acid (FA) in the presence of human and bovine serum albumins (HSA and BSA, respectively) has been investigated by steady-state irradiation, fluorescence, and laser flash photolysis (LFP). Spectroscopic measurements allowed for the determination of a 1:1 stoichiometry for the FA/SA complexes and pointed to a moderate binding of FA to the proteins; by contrast, the FA photoproducts were complexed more efficiently with SAs. Covalent photobinding to the protein, which is directly related to the photoallergic properties of the drug, was detected after long irradiation times and was found to be significantly higher in the case of BSA. Intermolecular FA-amino acid and FA-albumin irradiations resulted in the formation of photoproducts arising from coupling between both moieties, as indicated by mass spectrometric analysis. Mechanistic studies using model drug-amino acid linked systems indicated that the key photochemical step involved in photoallergy is formal hydrogen atom transfer from an amino acid residue to the excited benzophenone chromophore of FA or (more likely) its photoproducts. This results in the formation of caged radical pairs followed by C-C coupling to give covalent photoaducts.
authors.affiliation: Departamento de Química/Instituto de Tecnología Química UPV-CSIC, Universitat Politècnica de València , Camino de Vera s/n, 46022 Valencia, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Vayá
authors.affiliation: Unidad Mixta de Investigación IIS La Fe-UPV, Hospital Universitari i Politècnic La Fe , Avenida de Fernando Abril Martorell 106, 46026 Valencia, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Andreu
authors.affiliation: Departamento de Química/Instituto de Tecnología Química UPV-CSIC, Universitat Politècnica de València , Camino de Vera s/n, 46022 Valencia, Spain.
authors.forename: Vicente T
authors.initials: VT
authors.lastname: Monje
authors.affiliation: Departamento de Química/Instituto de Tecnología Química UPV-CSIC, Universitat Politècnica de València , Camino de Vera s/n, 46022 Valencia, Spain.
authors.forename: M Consuelo
authors.initials: MC
authors.lastname: Jiménez
authors.affiliation: Departamento de Química/Instituto de Tecnología Química UPV-CSIC, Universitat Politècnica de València , Camino de Vera s/n, 46022 Valencia, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Miranda
mesh_terms: D000818:Animals; D002417:Cattle; D017454:Dermatitis, Photoallergic / Q000378:metabolism*; D011345:Fenofibrate / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry / Q000528:radiation effects; D006801:Humans; D007834:Lasers; D015394:Molecular Structure; D055668:Photochemical Processes / Q000528:radiation effects; D012709:Serum Albumin / Q000737:chemistry* / Q000528:radiation effects
chemical_list: D012709:Serum Albumin; C006012:fenofibric acid; D011345:Fenofibrate