2-(3-Benzoylphenyl)propanoic acid (ketoprofen), one of the nonsteroidal anti-inflammatory drugs, causes photocontact dermatitis by ultraviolet (UV) light as a side effect. In this study, we examined radical reactions induced by ketoprofen in the lipid membranes under UV irradiation using egg yolk phosphatidylcholine (egg-PC) liposomal membranes containing 5- or 16-doxyl stearic acid (5- or 16-DSA), which carry nitroxyl radical at the 5- or 16-position of the fatty acid chain, respectively. When the suspension of liposomal membrane was mixed with ketoprofen and irradiated with UV, electron spin resonance signal of 5- and 16-DSA in the membrane decreased. The decay consisted of fast decay and subsequent slow decay. The overall decay for 5-DSA was faster than that for 16-DSA. The rate of slower decay of 16-DSA increased with ketoprofen concentration. The bulk lipid in the membrane affected the rate of slower decay of 5-DSA; the rate increased with the amount of egg-PC and decreased in the rigid membrane composed of dipalmitoylphosphatidylcholine. When spin trapping studies with α-(4-pyridyl 1-oxide)-N-tert-butylnitrone (POBN) and 5,5-dimetyl-1-pyrroline-N-oxide (DMPO) were performed in ketoprofen solution, C-centered radical adducts of POBN and superoxide anion radical adducts of DMPO were detected after UV irradiation. POBN suppressed the signal decay of 5-DSA in the liposomal membrane, whereas superoxide dismutase accelerated it. These results support that ketoprofen penetrates the lipid membrane and induces a radical reaction near the polar region in the membrane, and that ketoprofen-related C-centered radical is involved in the radical reaction.

非甾体抗炎药之一，2-（3-苯甲酰基苯基）丙酸（酮洛芬），会因紫外线（UV）引起光接触性皮炎。在这项研究中，我们使用含有5或16-doxyl硬脂酸（5或16-DSA）的蛋黄磷脂酰胆碱（egg-PC）脂质体膜，其中带有硝酰羟基，研究了酮洛芬在紫外线照射下在脂质膜上引起的自由基反应。分别位于脂肪酸链的5或16位上的基团。当脂质体膜的悬浮液与酮洛芬混合并用紫外线照射时，膜中5-和16-DSA的电子自旋共振信号降低。衰减包括快速衰减和随后的缓慢衰减。5-DSA的总衰减比16-DSA的总衰减快。16-DSA的缓慢衰变速率随酮洛芬浓度的增加而增加。膜中的大量脂质影响了5-DSA的缓慢降解速率。随卵PC量的增加而增加，而由二棕榈酰磷脂酰胆碱组成的刚性膜则减少。当使用α-（4-吡啶基1-氧化物）-进行自旋捕获研究时ñ -叔-butylnitrone（POBN）和5,5-二甲亚-1- pyrroline- Ñ氧化物（DMPO）中酮洛芬溶液进行，C为中心的紫外线照射后，检测DMPO的自由基加合物POBN和超氧阴离子自由基的加合物。POBN抑制了脂质体膜中5-DSA的信号衰减，而超氧化物歧化酶则加速了它的降解。这些结果支持酮洛芬穿透脂质膜并在膜的极性区域附近引发自由基反应，并且酮洛芬相关的以C为中心的自由基参与自由基反应。