Photochemical study of the highly used corticosteroids dexamethasone and prednisone. Effects of micellar confinement and cytotoxicity analysis of photoproducts

CACCIARI, R. DANIEL; REYNOSO, EUGENIA; CANDELA, FLORENCIA MENIS; SABINI, CAROLA; MONTEJANO, HERNÁN A.; BIASUTTI, M. ALICIA

NEW JOURNAL OF CHEMISTRY

ROYAL SOC CHEMISTRY

Año: 2020

1144-0546

In order to investigate the effect of solar UV light on pharmacological compounds consider asenvironmental emerging pollutants, we studied the kinetic, mechanistic and toxicological aspectsof the direct photolysis of highly used anti-inflammatory corticosteroids: Dexamethasone andPrednisone. The photochemical experiments were done in aqueous media at different atmosphericconditions, with the purpose to discern the oxygen participation in the photodegradative processes.Moreover, the influence of direct micelles of different surfactants upon the corticosteroidsbehavior against UV light was evaluated, and the cytotoxicity of the photoproducts on Vero celllinewas tested as well.Through static and dynamic spectroscopic techniques it was possible to detect a dependencebetween the rate of the photodegradation and the availability of oxygen, since both corticosteroidsare capable of photosensitizing the generation of reactive oxygen species, mainly singlet oxygenand hydroxyl radical, by generating their respective triplet excited state (characterized for the firsttime in this work). Dexamethasone and Prednisone are inert to the action of singlet oxygen butsensitive to the effect of hydroxyl radical. Also, unimolecular photochemical reactions, namelyNorrish type I and II photo-rearrangements, occur due to the presence of carbonyl functionalgroups in the molecules structures.In the presence of direct micelles of anionic, cationic and non-ionic surfactants, a photoprotectiveeffect was observed for all corticosteroids studied. The protection phenomenon was attributed tothe interaction of the molecules with the micellar interfaces and their overall distribution inside thenon-polar micellar core. These behaviors seem to be in close relationship with the dipolar momentof each molecule.On the other hand, the in vitro cytotoxicity bioassays, MTT metabolism and neutral red uptake,reveal that the corticosteroids and their photoproducts obtained under different atmosphereconditions induce cell metabolic alterations at the mitochondrial level, and this effect could bemore significant than lysosomal damage. In most cases, photo-products are found to have greatertoxicity than the original drugs.Studies on micellar influence and cytotoxicity also included the corticosteroid prednisolone,whose photodegradation has been previously studied in homogeneous medium.