Laboratory of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan.
Laboratory of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan.
J Photochem Photobiol B. 2021 Jan;214:112090. doi: 10.1016/j.jphotobiol.2020.112090. Epub 2020 Nov 23.
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.
2-(3-苯甲酰基)丙酸（酮洛芬）是一种非甾体抗炎药，它会引起光接触性皮炎，这是其副作用之一。在这项研究中，我们使用含有 5-或 16-二氧代硬脂酸（5-或 16-DSA）的蛋黄卵磷脂（egg-PC）脂质体囊泡来研究酮洛芬在紫外线（UV）照射下诱导的脂膜中的自由基反应，5-或 16-DSA 在脂肪酸链的 5-或 16-位上带有氮氧自由基。当脂质体囊泡悬浮液与酮洛芬混合并受到 UV 照射时，膜中的 5-DSA 和 16-DSA 的电子自旋共振信号会减弱。衰减包括快速衰减和随后的缓慢衰减。5-DSA 的整体衰减速度快于 16-DSA。膜中 16-DSA 的较慢衰减速率随酮洛芬浓度的增加而增加。膜中的体相脂质会影响 5-DSA 的较慢衰减速率；该速率随 egg-PC 的量增加而增加，并在由二棕榈酰基磷脂酰胆碱组成的刚性膜中降低。当在酮洛芬溶液中进行 α-(4-吡啶 1-氧化物)-N-叔丁基氮氧化物（POBN）和 5,5-二甲基-1-吡咯啉-N-氧化物（DMPO）的自旋捕获研究时，在紫外线照射后检测到 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 抑制了脂质体囊泡中 5-DSA 的信号衰减，而超氧化物歧化酶则加速了它。这些结果表明酮洛芬穿透脂膜，并在膜的极性区域附近诱导自由基反应，并且酮洛芬相关的 C 中心自由基参与了自由基反应。
