title: UV-light effects on cytochrome c modulated by the aggregation state of phenothiazines.
abstract: The present study shows the factors that modulate the photodamage promoted by phenothiazines. Cytochrome c was irradiated with UV light for 120 min, over a pH range from 4.0 to 8.0, in the absence and in the presence of different concentrations of thioridazine (TR) and fluphenazine (FP). In the absence of phenothiazines, the maximal rate of a Soret band blue shift (nm/min) from 409 to 406 nm was obtained at pH 4.0 (0.028 nm/min). The presence of phenothiazines at the concentration range 10-25 µmol/L amplified and accelerated a cytochrome c blue shift (409 to 405 nm, at a rate = 0.041 nm/min). Above 25 µmol/L, crescent concentrations of phenothiazines contributed to cytochrome c protection with (maximal at 2500 µmol/L). Scanning electronic microscopy revealed the formation of nanostructures. The pH also influenced the effect of low phenothiazine concentrations on cytochrome c. Thus, the predominance of phenothiazine-promoted cytochrome c damage or protection depends on a balance of the following factors: the yield of photo-generated drug cation radicals, which is favored by acidic pH; the stability of the cation radicals, which is favored by the drug aggregation; and the cytochrome c structure, modulated by the pH.
authors.affiliation: NanoBioMAv, Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP, Brazil ; Universidade de Mogi das Cruzes UMC, Mogi das Cruzes, SP, Brazil.
authors.forename: Carolina G
authors.initials: CG
authors.lastname: dos Santos
authors.forename: André L
authors.initials: AL
authors.lastname: Silva
authors.forename: Flavio L
authors.initials: FL
authors.lastname: Souza
authors.forename: Alexandre J C
authors.initials: AJ
authors.lastname: Lanfredi
authors.forename: Paolo
authors.initials: P
authors.lastname: Di Mascio
authors.forename: Otaciro R
authors.initials: OR
authors.lastname: Nascimento
authors.forename: Tiago
authors.initials: T
authors.lastname: Rodrigues
authors.forename: Iseli L
authors.initials: IL
authors.lastname: Nantes
mesh_terms: D000818:Animals; D045304:Cytochromes c / Q000737:chemistry* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005476:Fluphenazine / Q000737:chemistry* / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D010084:Oxidation-Reduction / Q000187:drug effects / Q000528:radiation effects; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology; D013881:Thioridazine / Q000737:chemistry* / Q000494:pharmacology*; D014466:Ultraviolet Rays
chemical_list: D005609:Free Radicals; D017319:Photosensitizing Agents; D045304:Cytochromes c; D013881:Thioridazine; D005476:Fluphenazine