Chignell C F, Sik R H
Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
Photochem Photobiol. 1998 May;67(5):591-5.
Ultraviolet irradiation (lambda > 300 nm) of the nonsteroidal anti-inflammatory agent ketoprofen (KP, 3-benzoyl-alpha-methylbenzoacetic acid) in aqueous solution, pH 7.4, results in heterolytic decarboxylation of the drug to give 3-ethylbenzophenone (EtBP). Ketoprofen caused the photohemolysis of human erythrocytes probably as a result of lipid peroxidation. Application of a static magnetic field (250-1500 G) during UV (> 300 nm) irradiation of KP and erythrocytes significantly decreased the time required for photohemolysis. This observation suggests that KP-induced photohemolysis involves the initial generation of a triplet radical pair derived from the reaction of triplet state KP (or 3-EtBP) with erythrocyte component(s) probably lipids. The magnetic field increases the concentration and/or lifetime of free radicals that escape from the radical pair so that the critical radical concentration needed to initiate membrane damage and cause cell lysis is reached sooner. Spin-trapping studies with 2,6-dibromo-1-nitrosobenzene-4-sulfonate confirmed that the application of an external static magnetic field increased the concentration of radicals released during the photolysis of either KP or 3-EtBP dissolved in organized media such as sodium dodecylsulfate micelles.
在pH 7.4的水溶液中,对非甾体抗炎药酮洛芬(KP,3-苯甲酰基-α-甲基苯乙酸)进行紫外线照射(波长> 300 nm),会导致该药物发生异裂脱羧反应,生成3-乙基二苯甲酮(EtBP)。酮洛芬可能由于脂质过氧化作用导致人红细胞发生光溶血。在对酮洛芬和红细胞进行紫外线(> 300 nm)照射期间施加静磁场(250 - 1500 G),可显著缩短光溶血所需时间。这一观察结果表明,酮洛芬诱导的光溶血涉及由三线态酮洛芬(或3-乙基二苯甲酮)与红细胞成分(可能是脂质)反应产生的三线态自由基对的初始生成。磁场增加了从自由基对中逸出的自由基的浓度和/或寿命,从而使引发膜损伤并导致细胞裂解所需的临界自由基浓度更快达到。用2,6-二溴-1-亚硝基苯-4-磺酸盐进行的自旋捕获研究证实,施加外部静磁场会增加溶解在有组织介质(如十二烷基硫酸钠胶束)中的酮洛芬或3-乙基二苯甲酮光解过程中释放的自由基浓度。