STUDIES ON THE NATURE OF INVITRO AND INVIVO PHOTOSENSITIZATION REACTIONS BY PSORALENS AND PORPHYRINS
STUDIES ON THE NATURE OF INVITRO AND INVIVO PHOTOSENSITIZATION REACTIONS BY PSORALENS AND PORPHYRINS
复制标题
DOI：
10.1111/1523-1747.ep12455986
复制
发表时间：
1988-03-01
影响因子：
6.5
通讯作者：
PATHAK, MA
中科院分区：
文献类型：
--
作者：
CARRARO, C;PATHAK, MA
本研究旨在探讨第二类(光动力)反应在皮肤光敏剂诱导的体外和体内光敏反应中的作用。作为内源性和外源性光敏剂模型化合物的几种卟啉和补骨脂素被检测为：(A)产生单线态氧和超氧阴离子，(B)诱导膜和相关微粒体P-450的损伤，(C)促进肝脏和表皮细胞微粒体脂的脂质过氧化，以及(D)在体内诱导皮肤光敏反应。体外H2O和D2O中单线态氧产生的剂量-反应研究以及特定猝灭剂对单线态氧和超氧阴离子产生的抑制研究表明，在10-5M和10-6M浓度和1-5J/cm2的UVA(>；320-400 nm辐射)照射剂量下，卟啉产生的单线态氧显著高于补骨脂素5-20倍。对豚鼠表皮和肝脏微粒体P-450需氧光降解的比较研究表明，卟啉对P-450的破坏明显大于补骨脂素。一项涉及丙二醛产生的膜-脂过氧化研究，使用肝脏和表皮微体部分，在有和没有卟啉、补骨脂素和UVA辐射的情况下，表明UVA和卟啉产生的丙二醛是补骨脂素的10-20倍。卟啉不产生超氧阴离子。然而，补骨脂同时产生1O2和O2-。局部应用叠氮钠、1，4-二氮杂双环[2，2，2]-辛烷、β-胡萝卜素、山梨醇和超氧化物歧化酶可选择性地抑制补骨脂素对豚鼠皮肤的光敏作用(红斑和水肿症)，表明单线态氧和超氧阴离子在补骨脂素诱导的皮肤光敏作用中起主要作用。研究表明，卟啉的光敏化主要是以富含脂质的膜和与之相关的血红素蛋白P-450为靶标的氧依赖的II型光动力反应，涉及作为主要中间体的单线态氧的产生，而不是超氧阴离子。补骨脂素不仅引起以DNA为靶点的I型缺氧反应，而且还引起以破坏富脂细胞膜和P-450为靶点的II型氧依赖过氧化反应。
This study was directed to examine the role of type II (photodynamic) reactions involving the production of reactive oxygen species (singlet oxygen, superoxide anion, and hydroxy radicals) in in vitro and in vivo photosensitization reactions induced by skin photosensitizing chemicals. Several porphyrins and psoralens, as model compounds representing examples of endogenous and exogenous photosensitizers, were examined for their ability to (a) produce singlet oxygen and superoxide anions, (b) induce damage to membranes and associated microsomal P-450, (c) promote lipid peroxidation of microsomal lipids of liver and epidermal cells, and (d) induce skin photosensitization reactions in vivo. Dose-response study in vitro of singlet oxygen production in H2O and D2O and inhibition studies involving the production of singlet oxygen and superoxide anion by specific quenchers indicated significant production of singlet oxygen by porphyrins, about 5-20 times higher than psoralen at 10-5M and 10-6 M concentration and irradiation dose of 1-5 J/cm2 of UVA (> 320-400 nm radiation). The comparative studies on aerobic photodegradation of microsomal P-450 of guinea pig epidermis and liver indicated a significantly greater destruction of P-450 with porphyrins than with psoralens. A membrane-lipid peroxidation study involving malondialdehyde production, using liver and epidermal microsomal fractions with and without porphyrins, psoralens, and UVA radiation, indicated 10-20 times increased production of malondialdehyde with UVA and porphyrins than with psoralens. Porphyrins did not produce superoxide anion. Psoralens, however, produced both 1O2 and O2-. In vivo photosensitization by psoralens in guinea pig skin (erythema and edema) could be selectively inhibited by the topical application of sodium azide, 1,4-diazabicyclo-[2,2,2]-octane, .beta.-carotene, sorbitols, and superoxide dismutase, indicating a major role of singlet oxygen and also superoxide anion in psoralen-induced skin photosensitization. The study indicates that porphyrin photosensitization is primarily an oxygen-dependent, type II, photodynamic reaction targeted to lipid-rich membranes and heme protein P-450 associated therein and involves the production of singlet oxygen as a major intermediate but not superoxide anion. Psoralens evoke not only a type I anoxic reaction targeted to DNA but also a type-II oxygen-dependent peroxidation reaction targeted to damage lipid-rich cell membranes and P-450.