Matsuo I, Fujita H, Hayakawa K, Ohkido M
J Invest Dermatol. 1986 Nov;87(5):637-41. doi: 10.1111/1523-1747.ep12456307.
We examined the lipid peroxidative potency and photohemolytic activity of thiazide diuretics, especially penflutizide (PFZ), to determine the molecular mechanism of thiazide phototoxicity. Ultraviolet A irradiation of squalene in the presence of PFZ, hydrochlorothiazide, methiclothiazide, benzylhydrochlorothiazide, or trichlormethiazide induced in vitro peroxidation as measured by production of the hydroperoxides and thiobarbituric acid-reactive substances. Among the thiazides, PFZ showed the highest potency to photooxidize lipids. PFZ-photosensitized peroxidation of squalene was repressed by the presence of sodium azide or 2,5-dimethylfuran and was accelerated in a D2O suspension. These findings suggest the participation of singlet oxygen in PFZ photoperoxidation of squalene (type II mechanism). PFZ-photosensitized lysis of red blood cells (RBC) accompanied by formation of hydroperoxides in RBC membrane lipids was also noted. These results suggest that membrane lipids can be one of the target molecules of thiazide phototoxicity.
我们研究了噻嗪类利尿剂，尤其是戊氟噻嗪（PFZ）的脂质过氧化能力和光溶血活性，以确定噻嗪类药物光毒性的分子机制。在PFZ、氢氯噻嗪、甲氯噻嗪、苄基氢氯噻嗪或三氯噻嗪存在的情况下，紫外线A照射角鲨烯可诱导体外过氧化，通过氢过氧化物和硫代巴比妥酸反应性物质的产生来衡量。在这些噻嗪类药物中，PFZ对脂质光氧化的能力最强。叠氮化钠或2,5 - 二甲基呋喃的存在可抑制PFZ介导的角鲨烯光敏过氧化，而在重水悬浮液中则加速过氧化。这些发现表明单线态氧参与了PFZ对角鲨烯的光过氧化反应（II型机制）。还观察到PFZ介导的红细胞（RBC）裂解，同时红细胞膜脂质中形成氢过氧化物。这些结果表明膜脂质可能是噻嗪类药物光毒性的靶分子之一。
