MECHANISMS OF CHEMICALLY INDUCED PHOTOSENSITIVITY

化学诱导光敏性的机制

• 批准号: 3965262
• 负责人: C F CHIGNELL
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3965262
• 关键词: anthracenes; biophysics; chlorpromazine; electron spin resonance spectroscopy; free radicals; molecular biology; nonvisual photosensitivity; oxazoles; physical chemical interaction; porphyrins; radiobiology; skin disorder; superoxides; ultraviolet radiation

Light is known to interact with endogenous or exogenous chemical agents in the skin or eyes, to produce photosensitization (phototoxicity or photoallergy). The objective of this study is to determine whether light-induce free radicals or active oxygen species play a role in photosensitization. Chlorpromazine (CPZ) is an antipsychotic drug that causes both phototoxic and photoallergic reactions. UV irradiation (330 nm) of CPZ in aqueous solution resulted in the homolytic cleavage of the carbon-chlorine bond to yield an aryl radical which extracted a hydrogen atom from suitable donors. CPZ photoionized when irradiated at 280 nm (but not at 330 nm) to give the CPZ cation radical. CPZ generated singlet oxygen (luminescence at 1270 nm) when photo-irradiated in benzene, hexane, and cyclohexane (strong), and methanol, and ethanol (weak) but not in aqueous solutions. CPZ sulfoxide, a major CPZ metabolite in man, generated .OH and the CPZ cation radical upon irradiation with near UV light. Halogenated salicylanilides eg. 3,3', 4', 5-tetrachlorosalicylanilide (TCSA) and 3,4'5-tribromosalicylanilide (TBSA) generated aryl radicals during photo-irradiation. Irradiation of TBSA with glutathione generated the corresponding thiyl radical, while under the same conditions TCSA abstracted hydrogen atom from the glycyl Alpha-carbon atom of the dipeptide Gly-Ala. The skin photoallergy of TBSA or TCSA may be due to reactions involving protein-derived radical intermediates. The chlorinated phenols bithionol and fentichlor also dehalogenated upon irradiation and in addition underwent photohydrolysis to yield semiquinone radicals. The aryl radical formed by photodeiodination of the anti-arrhythmic drug amiodarone readily abstracted a hydrogen atom from linoleic acid. Reaction of the resultant linoleyl radical with oxygen would initiate lipid peroxidation and provide an explanation for lipofuscin skin deposits in patients receiving this drug.

已知光与内源性或外源性化学试剂相互作用 皮肤或眼睛，产生光敏作用（光毒性或 光过敏）。 本研究的目的是确定是否 光诱导自由基或活性氧物种发挥作用 光敏化。 氯丙嗪 (CPZ) 是一种抗精神病药物 引起光毒性和光过敏反应。 紫外线照射（330 nm）的CPZ在水溶液中导致了均裂 碳-氯键产生芳基，提取氢 来自合适的供体的原子。 CPZ 在 280 nm 照射时发生光离子化（但 不在 330 nm 处）得到 CPZ 阳离子自由基。 CPZ 生成单峰 在苯、己烷、 和环己烷（强）、甲醇和乙醇（弱），但不在 水溶液。 CPZ 亚砜是人体中主要的 CPZ 代谢物，产生 .OH 和 CPZ 阳离子自由基在近紫外光照射下。 卤代水杨酰苯胺例如。 3,3',4',5-四氯水杨酰苯胺 (TCSA) 和 3,4'5-三溴水杨酰苯胺 (TBSA) 生成芳基自由基 在光照射期间。 用生成的谷胱甘肽照射 TBSA 相应的硫基自由基，而在相同条件下TCSA 从二肽的甘氨酰α-碳原子中提取氢原子 甘氨酸-丙氨酸。 TBSA或TCSA的皮肤光过敏反应可能是由于 涉及蛋白质衍生的自由基中间体。 氯化酚类 联硫醇和芬杀氯在辐射和环境下也会脱卤。 加成经过光水解产生半醌自由基。 芳基 抗心律失常药物胺碘酮光脱碘形成的自由基 很容易从亚油酸中夺取一个氢原子。 的反应 与氧产生的亚油基自由基会引发脂质过氧化 并对患者皮肤脂褐素沉积提供解释 接受这种药物。