MECHANISMS OF CHEMICALLY INDUCED PHOTOSENSITIVITY

化学诱导光敏性的机制

• 批准号: 4693233
• 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/4693233
• 关键词: anthracenes; chlorpromazine; electron spin resonance spectroscopy; free radicals; 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). While the initial step in all forms of photosensitivity must be the absorption of light by the chemical or its metabolites, the precise mechanisms of sensitization are unknown. The objective of this study is to determine whether light-induced 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 of CPZ in aqueous solution resulted in the homolytic cleavage of the carbon-chlorine bond and the generation of an aryl radical which extracted a hydrogen atom from suitable donors. CPZ also photo-ionized when irradiated at 280 nm to give the CPZ cation radical. Thus, it appears unlikely that the CPZ cation radical is involved in the phototoxicity of this drug. CPZ generated singlet oxygen (phosphorescence at 1270 nm) when irradiated in benzene, hexane and cyclohexane but not in aqueous or alcoholic solutions. The CPZ sulfoxide, which is formed in humans and other mammalian species, generated the hydroxyl radical and CPZ cation radical upon irradiation with near UV light. Hematoporphyrin derivative (HPD) and light convert oxygen to hydroxyl free radical and hydrogen peroxide in the presence of light. HPD and light also initiated an oxygen-dependent formation of thiyl radical from cysteine. Halogenated salicylanilides eg. 3,3',4',5-tetrachlorosalicylanilide (TCSA), 3,4',5-tribromosalicylanilide, (TBSA) and N-butyl-4-chlorosalicylanilide (buclosamide) all generated aryl radicals during photodehalogenation. Irradiation of TBSA with glutathione or cysteine resulted in the generation of the corresponding thiyl radicals. Thus, it appears possible that the skin photoallergy of these compounds may result from the reaction of these radicals with proteins to form antigens.

已知光与体内的内源性或外源性化学物质相互作用