In vitro photoperoxidation as an indicator of the potential phototoxicity of non-steroidal anti-inflammatory 2-arylpropionic acids.
The photochemical behaviour of 2-arylpropionic acids involves the intermediacy of short-lived species such as drug-derived peroxides and/or free radicals. Although peroxides are expected to undergo very rapid breakdown, this study shows that they can be detected in the photomixtures by the peroxidase-catalysed oxidation of dichlorodihydrofluorescein to its fluorescent analogue. Their possible contribution to phototoxicity has been evaluated by red blood cell membrane lysis. The shorter lives of organic free radicals prevent their direct determination in the irradiation mixtures; however, the results strongly suggest that these intermediates have a key role in the phototoxicity of 2-arylpropionic acids, through induction of photodynamic lipid peroxidation. This has been determined using linoleic acid as a model lipid, and measuring the spectrophotometric absorption at 233 nm associated with the formation of dienic hydroperoxides. It is probable that a similar process is responsible for the photochemically induced damage to cell membranes observed in the photohaemolysis assays.
Miranda
M A
MA
Departamento de Quimica/Instituto de Tecnologia Quimica UPV-CSIC, Universidad Politecnica, Apartado 22012, E-46071-Valencia, Spain.
Castell
J V
JV
Gómez-Lechón
M J
MJ
Martinez
L A
LA