Radical reactions induced by ketoprofen in phospholipid membranes under ultraviolet light irradiation
Radical reactions induced by ketoprofen in phospholipid membranes under ultraviolet light irradiation
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DOI：
10.1016/j.jphotobiol.2020.112090
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发表时间：
2021-01-01
影响因子：
5.4
通讯作者：
Takeshita, Keizo
中科院分区：
文献类型：
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作者：
Okazaki, Shoko;Hirata, Ayako;Takeshita, Keizo
2-（3-苯甲酰基苯基）丙酸（酮洛芬），一种非甾体抗炎药，可引起紫外线（UV）光接触性皮炎。在这项研究中，我们研究了自由基反应酮洛芬在脂质膜紫外线照射下使用蛋黄磷脂酰胆碱（鸡蛋PC）脂质体膜含有5或16-doxyl硬脂酸（5或16-DSA），携带硝酰基自由基在5或16-位的脂肪酸链，分别。将脂质体膜混悬液与酮洛芬混合后，经紫外光照射，膜中5-和16-DSA的电子自旋共振信号减弱。衰变由快速衰变和随后的缓慢衰变组成。5-DSA的总衰减比16-DSA快。16-DSA的缓慢衰减速率随酮洛芬浓度增加而增加。在膜中的散装脂质影响的速度较慢的衰减的5-DSA的速度增加，蛋-PC的量和减少的刚性膜组成的二棕榈酰磷脂酰胆碱。当在酮洛芬溶液中进行α-（4-吡啶基1-氧化物）-N-叔丁基硝酮（POBN）和5，5-二甲基-1-吡咯啉-N-氧化物（DMPO）的自旋捕获研究时，在UV照射后检测到POBN的C中心自由基加合物和DMPO的超氧阴离子自由基加合物。POBN抑制5-DSA信号在脂质体膜上的衰减，而超氧化物歧化酶则加速其衰减.这些结果支持酮洛芬穿透脂质膜并在膜的极性区附近诱导自由基反应，且酮洛芬相关的C-中心自由基参与了自由基反应.
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 5or 16-doxyl stearic acid (5or 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 5and 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 alpha-(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.