The Physicochemical Basis of Clofazimine-Induced Skin Pigmentation.
The Physicochemical Basis of Clofazimine-Induced Skin Pigmentation.
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DOI：
10.1016/j.jid.2017.09.031
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Rosania GR
中科院分区：
文献类型：
--
作者：
Murashov MD;LaLone V;Rzeczycki PM;Keswani RK;Yoon GS;Sud S;Rajeswaran W;Larsen S;Stringer KA;Rosania GR
氯法齐明是一种弱碱性，FDA批准的抗生素，由世界卫生组织推荐用于治疗麻风病和耐多药结核病。在长期治疗后，氯法齐明在整个生物体中广泛生物蓄积和沉淀，形成晶体样药物包涵体（CLDIs）。由于药物的红色，人们普遍认为氯法齐明的生物蓄积导致皮肤色素沉着，这是其最常见的副作用。为了测试氯法齐明诱导的皮肤色素沉着是否是由于CLDI形成，我们合成了一种密切相关的氯法齐明类似物，其在CLDI形成所需的生理pH和氯化物条件下不沉淀。尽管小鼠中没有可检测到的CLDI，但给予这种类似物仍然会导致显着的皮肤色素沉着。在氯法齐明处理的小鼠中，当用专门设计用于检测氯法齐明聚集体的显微成像系统分析时，皮肤冷冻切片未显示CLDIs的证据。相反，皮肤的反射光谱揭示了对应于药物的可溶性游离碱形式的信号。与皮肤中氯法齐明的低浓度一致，这些结果表明氯法齐明诱导的皮肤色素沉着不是由于氯法齐明沉淀和CLDI形成，而是由于药物的循环游离碱形式分配到皮下脂肪中。
Clofazimine is a weakly basic, FDA-approved antibiotic recommended by the World Health Organization to treat leprosy and multi-drug-resistant tuberculosis. Upon prolonged treatment, clofazimine extensively bioaccumulates and precipitates throughout the organism, forming crystal-like drug inclusions (CLDIs). Because of the drug's red color, it is widely believed that clofazimine bioaccumulation results in skin pigmentation, its most common side effect. To test whether clofazimine-induced skin pigmentation is due to CLDI formation, we synthesized a closely related clofazimine analog that does not precipitate under physiological pH and chloride conditions that are required for CLDI formation. Despite the absence of detectable CLDIs in mice, administration of this analog still led to significant skin pigmentation. In clofazimine treated mice, skin cryosections revealed no evidence of CLDIs when analyzed with a microscopic imaging system specifically designed for detecting clofazimine aggregates. Rather, the reflectance spectra of the skin revealed a signal corresponding to the soluble, free base form of the drug. Consistent with the low concentrations of clofazimine in the skin, these results suggest that clofazimine-induced skin pigmentation is not due to clofazimine precipitation and CLDI formation, but rather to the partitioning of the circulating, free base form of the drug into subcutaneous fat.
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影响因子：
3.7
作者：
Keswani, Rahul K.;Yoon, Gi S.;Rosania, Gus R.
通讯作者：
Rosania, Gus R.
DOI：
10.1088/2040-8978/15/9/094007
发表时间：
2013-09-01
期刊：
Journal of optics (2010)
影响因子：
--
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通讯作者：
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影响因子：
15.1
作者：
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通讯作者：
Rosania, Gus R.
影响因子：
4.9
作者：
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通讯作者：
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