Effects of the isoflavone 4',5,7-trihydroxyisoflavone (genistein) on psoralen plus ultraviolet A radiation (PUVA)-induced photodamage.
Effects of the isoflavone 4',5,7-trihydroxyisoflavone (genistein) on psoralen plus ultraviolet A radiation (PUVA)-induced photodamage.
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异黄酮 4,5,7-三羟基异黄酮（金雀异黄酮）对补骨脂素加紫外线 A 辐射 (PUVA) 诱导的光损伤的影响。
DOI：
10.1093/carcin/23.2.317
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发表时间：
2002
期刊：
影响因子：
4.7
通讯作者：
Wei,Huachen
中科院分区：
文献类型：
--
作者：
Shyong,EileenQ;Lu,Yuhun;Lazinsky,Alison;Saladi,RaoN;Phelps,RobertG;Austin,LisaM;Lebwohl,Mark;Wei,Huachen
长期补骨脂素加紫外线 A 辐射 (PUVA) 治疗会增加鳞状细胞癌和恶性黑色素瘤的风险。金雀异黄酮（4',5,7-三羟基异黄酮）是大豆中的一种主要异黄酮，也是蛋白酪氨酸激酶的特异性抑制剂，已被证明可以抑制无毛小鼠中 UVB 诱导的皮肤癌发生。在这项研究中，我们检查了外用金雀异黄酮对 PUVA 引起的光损伤的保护作用。在两个独立的实验中，在 8-甲氧基补骨脂素给药后 1 小时和 UVA 照射前 1 小时，将二甲基亚砜/丙酮 (1:9) 溶液中的金雀异黄酮应用于 SKH-1 雌性小鼠。使用金雀异黄素可显着减少 PUVA 引起的皮肤增厚，并以剂量依赖性方式大大减少皮肤红斑和溃疡。组织学检查表明，PUVA 治疗小鼠皮肤引起了整个表皮的剧烈炎症变化；外用金雀异黄素可防止这些变化，且没有明显的副作用。与未暴露的对照皮肤相比，经 PUVA 处理的皮肤中含有裂解的聚（ADP-核糖）聚合酶（PARP）和活性 caspase-3 的细胞显着增加（分别为 P<0.05 和 P<0.0001）。局部金雀异黄素完全抑制 PARP 和 caspase-3 的裂解。在表皮基底上层区域观察到增殖细胞核抗原 (PCNA) 阳性细胞，并且与对照样品和用 PUVA 加外用染料木黄酮处理的样品相比，在 PUVA 处理的皮肤中，增殖细胞核抗原 (PCNA) 阳性细胞显着减少 (P<0.005)。这些结果表明金雀异黄素可以保护皮肤免受 PUVA 引起的光损伤。
Long-term psoralen plus ultraviolet A radiation (PUVA) therapy is associated with an increased risk of squamous cell carcinoma and malignant melanoma. Genistein (4′,5,7-trihydroxyisoflavone), a major isoflavone in soybeans and a specific inhibitor of protein tyrosine kinase, has been shown to inhibit UVB induced skin carcinogenesis in hairless mice. For this study we examined the protective effects of topical genistein on PUVA-induced photodamage. In two separate experiments, genistein in a dimethyl sulfoxide/acetone (1:9) solution was applied to SKH-1 female mice 1 h post 8-methoxy-psoralen dosing and 1 h prior to UVA irradiation. Application of genistein significantly decreased PUVA-induced skin thickening, and greatly diminished cutaneous erythema and ulceration in a dose-dependent manner. Histological examination showed that PUVA treatment of mouse skin induced dramatic inflammatory changes throughout the epidermis; topical genistein prevented these changes without noticeable adverse effects. Cells containing cleaved poly(ADP-ribose) polymerase (PARP) and active caspase-3 were significantly increased in PUVA-treated skin (P< 0.05 andP< 0.0001, respectively) as compared with unexposed control skin. Topical genistein completely inhibited cleavage of PARP and caspase-3. Proliferating cell nuclear antigen (PCNA) positive cells were observed in suprabasal areas of the epidermis and were significantly decreased in PUVA-treated skin compared with both control samples and samples treated with PUVA plus topical genistein (P< 0.005). These results indicate that genistein protects the skin from PUVA-induced photodamage.