Miranda M A, Castell J V, Gómez-Lechón M J, Martinez L A
Departamento de Quimica/Instituto de Tecnologia Quimica UPV-CSIC, Universidad Politecnica, Apartado 22012, E-46071-Valencia, Spain.
Toxicol In Vitro. 1993 Jul;7(4):523-6. doi: 10.1016/0887-2333(93)90058-d.
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.
2-芳基丙酸的光化学行为涉及短寿命物种的中间体，如药物衍生的过氧化物和/或自由基。尽管过氧化物预计会迅速分解，但本研究表明，它们可以通过过氧化物酶催化二氯二氢荧光素氧化为其荧光类似物在光混合物中被检测到。它们对光毒性的可能贡献已通过红细胞膜裂解进行评估。有机自由基的寿命较短，无法在辐照混合物中直接测定；然而，结果强烈表明，这些中间体通过诱导光动力脂质过氧化在2-芳基丙酸的光毒性中起关键作用。这是使用亚油酸作为模型脂质，并测量与二烯氢过氧化物形成相关的233nm处的分光光度吸收来确定的。在光溶血试验中观察到的光化学诱导的细胞膜损伤可能是由类似过程引起的。
