Direct detection of diclofenac radical produced by ultraviolet irradiation using electron spin resonance method
Direct detection of diclofenac radical produced by ultraviolet irradiation using electron spin resonance method
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DOI：
10.3164/jcbn.19-91
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发表时间：
2020-05-01
影响因子：
2.4
通讯作者：
Sato, Keizo
中科院分区：
文献类型：
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作者：
Akazaki, Satomi;Aoki, Ryohei;Sato, Keizo
双氯芬酸是一种非甾体类抗炎药，因其具有较强的抗炎作用，在临床治疗中常被用作解热镇痛药。然而，双氯芬酸可引起损伤，胃肠道粘膜病变和皮肤光敏是主要的副作用。一般来说，光敏药物含有光敏化学位点，在紫外线照射下形成自由基，导致光毒性反应。因此，本研究主要关注双氯芬酸光敏反应中自由基的产生。采用直接电子自旋共振方法，阐明了双氯芬酸在紫外线照射下产生自由基的机理，并推测其可能产生光毒性。双氯芬酸在254 nm紫外光照射下，根据照射时间产生双氯芬酸自由基，并在室温下稳定存在30 min。紫外照射系统根据双氯芬酸剂量产生双氯芬酸自由基，直至2 mM。因此，双氯芬酸自由基可能直接或间接与各种生物分子发生反应，引起光毒性等副作用，并由于双氯芬酸自由基的稳定性而产生新的双氯芬酸药理学。
Diclofenac, a nonsteroidal anti-inflammatory drug, is commonly used as an antipyretic analgesic owing to its strong anti-inflammatory action in clinical treatment. However, diclofenac can cause injury, with gastrointestinal mucosal lesions and skin photosensitivity as the main side effects. In general, photosensitive drugs contain photosensitive chemical sites, and form free radicals under ultraviolet irradiation, leading to phototoxic reactions. Therefore, this study focuses on free radical production in photosensitive reactions of diclofenac. The free radical production mechanism of diclofenac under ultraviolet irradiation, which might result in photo-toxicity, was clarified using a direct electron spin resonance method. When diclofenac was irradiated with ultraviolet light (254 nm), diclofenac radicals were generated depending on the ultraviolet irradiation time and stably present for 30 min at room temperature. Diclofenac radicals were produced by the ultraviolet irradiation system depending on the dose of diclofenac until 2 mM. Therefore, diclofenac radicals might directly or indirectly react with various biomolecules to cause phototoxicity, other side effects, and new diclofenac pharmacology owing to its stability of diclofenac radicals.