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药物光敏化的分子机制。第3部分。双氯芬酸引起的光溶血作用。

Molecular mechanism of drug photosensitization. Part 3. Photohemolysis sensitized by diflunisal.

作者信息

De Guidi G, Chillemi R, Giuffrida S, Condorelli G, Cambria Famá M

机构信息

Dipartimento di Scienze Chimiche, Università di Catania, Italy.

出版信息

J Photochem Photobiol B. 1991 Aug;10(3):221-37. doi: 10.1016/1011-1344(91)85004-z.

DOI:10.1016/1011-1344(91)85004-z
PMID:1779277
Abstract

The lysis of red blood cells photosensitized by diflunisal (DFN) was investigated. Photohemolysis is inhibited by butylated hydroxyanisole and reduced glutathione, but is unaffected by mannitol and enhanced by sodium azide; the presence of oxygen markedly reduces the lysis which is accelerated in anaerobic conditions. These results contrast with those expected for a photodynamic mechanism. High lytic activity is observed for pre-irradiated solutions, mainly under anaerobic conditions. Direct irradiation of DFN in buffer solution at pH 7.4 leads to the formation, under anaerobic conditions, of compound 2'-(2''',4'''-difluoro-3''-carboxy-[1'',1'''-biphenyl]-4''-oxy)-4'- fluoro-4-hydroxy-[1,1'-biphenyl]-3-carboxylic acid (PhP), whereas under aerobic conditions formation of PhP is accompanied by unidentified photo-oxidation products; only compound PhP displays strong lytic activity. The overall results for DFN-photosensitized hemolysis suggest a mechanism involving a concerted action of free radicals, superoxide anion, singlet oxygen and sensitizer photoproducts.

摘要

研究了双氟尼酸(DFN)光敏化导致的红细胞裂解。光溶血作用受到丁基化羟基茴香醚和还原型谷胱甘肽的抑制,但不受甘露醇影响,且被叠氮化钠增强;氧气的存在显著降低裂解作用,而在厌氧条件下裂解作用会加速。这些结果与光动力机制预期的结果相反。对于预辐照溶液,主要在厌氧条件下观察到高裂解活性。在pH 7.4的缓冲溶液中直接辐照DFN,在厌氧条件下会生成化合物2'-(2''',4'''-二氟-3''-羧基-[1'',1'''-联苯]-4''-氧基)-4'-氟-4-羟基-[1,1'-联苯]-3-羧酸(PhP),而在有氧条件下,PhP的形成伴随着未鉴定的光氧化产物;只有化合物PhP表现出强烈的裂解活性。DFN光敏化溶血的总体结果表明其机制涉及自由基、超氧阴离子、单线态氧和敏化剂光产物的协同作用。

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