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 光诱导的自由基或活性氧物质在 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 结果表明，CPZ在水溶液中的均裂作用导致了CPZ的均裂。 碳-氯键，产生芳基， 合适的供体。 CPZ在280 nm照射时光电离（但 不是在330 nm处），得到CPZ阳离子自由基。 CPZ生成单态 氧（在1270 nm处发光），当在苯，己烷， 和环己烷（强），甲醇，乙醇（弱），但不是在 水溶液。 CPZ亚砜是CPZ在人体内的主要代谢产物， OH和CPZ阳离子自由基。 卤代水杨酰苯胺，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）生成的芳基自由基 在光照射期间。 产生谷胱甘肽的TBSA的辐照 相应的硫基自由基，而在相同的条件下TCSA 从二肽的甘氨酰α-碳原子中提取氢原子 甘丙氨酸 TBSA或TCSA的皮肤光过敏可能是由于反应 涉及蛋白质衍生的自由基中间体。 氯代酚 在辐照后，双硫磷醇和芬草胺也会脱卤， 加成反应经历光水解产生半醌自由基。 芳基 抗糖尿病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。 反应 亚油基自由基与氧的结合可引发脂质过氧化反应 并为患者的脂褐质皮肤沉积提供了解释 接受这种药物。