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.

已知光与内源或外源化学剂相互作用 皮肤或眼睛，产生光敏性（光毒性或 光理）。 这项研究的目的是确定是否 轻诱导自由基或活性氧在 光敏化。 氯丙嗪（CPZ）是一种抗精神病药 引起光毒性和光（光（光）反应。 紫外线照射（330 CPZ在水溶液中的NM）导致了均质的裂解 碳氯键产生芳基自由基，该芳基提取氢 来自合适的捐助者的原子。 CPZ在280 nm处得到照射时进行光电离（但是 不在330 nm处）给出CPZ阳离子自由基。 CPZ产生了单元 氧气（1270 nm的发光）在己烷苯在苯二下时， 和环己烷（强），甲醇和乙醇（弱），但不在 水溶液。 CPZ亚氧化物是人类的主要CPZ代谢物，生成 .OH和CPZ阳离子在辐照后激进，近乎紫外线。 卤代水杨酸盐，例如。 3,3'，4'，5-四氯水杨酸酯 （TCSA）和3,4'5-Tribromromromromromolylylanilide（TBSA）产生的芳基自由基 在照片 - 辐照过程中。 用谷胱甘肽生成的TBSA辐照 相应的硫基自由基，而在相同条件下TCSA 来自二肽的糖基α-碳原子的抽象氢原子 gly-ala。 TBSA或TCSA的皮肤光照可能是由于反应引起的 涉及蛋白质来源的自由基中间体。 氯化苯酚 Bithionol和Fentichlor在辐照和中也脱解。 添加进行了光水解以产生半喹酮自由基。 芳基 通过抗心律失常药物amiodarone的光降剂形成的自由基 很容易从亚油酸中提取氢原子。 反应 由氧气产生的亚麻烯基自由基将启动脂质过氧化 并为患者的脂蛋白皮肤沉积提供解释 接受这种药物。