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）。 而所有形式的光敏性的第一步 必须是化学物质或其代谢产物的光吸收， 敏化的精确机制尚不清楚。 这个目的 研究是确定光引起的自由基还是活性氧 物种在光敏化中起作用。 氯丙嗪（CPZ）是 引起光毒性和光（光（光过））的抗精神病药 反应。 CPZ在水溶液中的紫外线照射导致 碳氯键的均质裂解和产生 芳基自由基从合适的供体中提取氢原子。 CPZ 当在280 nm处得到照射以给出CPZ阳离子时，还将照片离子化 激进的。 因此，CPZ阳离子自由基似乎不太可能 在该药物的光毒性中。 CPZ产生的单线氧 （1270 nm处的磷光）在苯，己烷和 环己烷，但不在水性或酒精溶液中。 CPZ亚氧化物， 是由人类和其他哺乳动物物种形成的，产生了 辐射后，羟基自由基和CPZ阳离子自由基近紫外线 光。 血源性肾上腺素衍生物（HPD）和光转化为氧气 在光的存在下，羟基自由基和过氧化氢。 HPD 光还引发了硫基自由基的氧依赖性形成 来自半胱氨酸。 卤代水杨酸盐，例如。 3,3'，4'，5-四氯六氯苯胺（TCSA），3,4'，5-Tribromromolomylecylanilide， （TBSA）和N-丁基-4-氯氯苯胺（二氯糖酰胺）均产生芳基 在光降氢化过程中的自由基。 用谷胱甘肽辐射TBSA 或半胱氨酸导致相应的硫基 激进分子。 因此，似乎有可能的皮肤光荣 这些自由基与蛋白质的反应可能导致的化合物 形成抗原。