Inhibition of ultraviolet light-induced oxidative events in the skin and internal organs of hairless mice by isoflavone genistein.
Inhibition of ultraviolet light-induced oxidative events in the skin and internal organs of hairless mice by isoflavone genistein.
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DOI：
10.1016/s0304-3835(02)00240-9
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发表时间：
2002-11
期刊：
影响因子：
9.7
通讯作者：
Huachen Wei;Xueshu Zhang;Yan Wang;M. Lebwohl
中科院分区：
文献类型：
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作者：
Huachen Wei;Xueshu Zhang;Yan Wang;M. Lebwohl
我们之前已经证明，大豆异黄酮染料木黄酮可抑制紫外线 B (UVB) 诱导的无毛小鼠皮肤肿瘤发生。在本研究中，我们进一步研究了金雀异黄素抑制光致癌作用的可能机制，重点关注 UVB 诱导的氧化事件，包括体内过氧化氢 (H2O2) 的产生、脂质过氧化（以丙二醛，MDA 为代表）和 8-羟基-2'-脱氧鸟苷 (8-OHdG) 的形成。我们证明，亚急性暴露于 UVB 会显着增加无毛小鼠皮肤中的 H2O2、脂质过氧化物和 8-OHdG 水平。此外，长期暴露于低剂量UVB（0.9-1.2 kJ/m2，持续20周）不仅显着增加了小鼠表皮中的8-OHdG水平，而且还显着增加了除肾脏外的小鼠肝脏、大脑和脾脏等内脏器官中的8-OHdG水平。然而，金雀异黄素并不影响相同 UVB 暴露小鼠皮肤中 UVB 诱导的嘧啶二聚体的水平，表明金雀异黄素选择性抑制氧化性 DNA 损伤。 H2O2 的诱导与 UVB 能量密度无关，而 MDA 和 8-OHdG 的水平则以 UVB 能量密度依赖性方式诱导。结果表明，H2O2 是皮肤对 UVB 照射的急性反应而产生的，而 MDA 和 8-OHdG 则随着 UVB 照射的增加而积累，并且与 UVB 照射的慢性影响密切相关。在 UVB 照射前 1 小时用 10 μmol 金雀异黄素预处理动物，可显着抑制 UVB 诱导的皮肤中的 H2O2 和 MDA 以及表皮和内脏中的 8-OHdG。金雀异黄酮对 8-OHdG 形成的抑制作用已在经 UVA 和 B 照射的纯化 DNA 中得到证实。总而言之，我们的结果表明 UVB 照射会引发一系列氧化事件，异黄酮金雀异黄素可通过直接猝灭活性氧或间接抗炎作用来显着抑制氧化事件。因此，金雀异黄素的抗氧化特性可以解释金雀异黄素抗光致癌作用的机制。
We have previously demonstrated that soybean isoflavone genistein inhibits ultraviolet-B (UVB)-induced skin tumorigenesis in hairless mice. In the present study, we further investigated the possible mechanism(s) of action whereby genistein inhibits photocarcinogenesis with focuses on UVB-induced oxidative events, including hydrogen peroxide (H2O2) production, lipid peroxidation (as represented by malondialdehyde, MDA), and 8-hydroxy-2′-deoxyguanosine (8-OHdG) formation in vivo. We demonstrated that subacute exposure to UVB substantially increased the level of H2O2, lipid peroxides, and 8-OHdG in skin of hairless mice. In addition, chronic exposure to low-dose UVB (0.9–1.2 kJ/m2for 20 weeks) substantially increased the levels of 8-OHdG not only in the epidermis, but also in the internal organs such as liver, brain, and spleen of mice with exception of kidney. However, genistein did not affect the level of UVB-induced pyrimidine dimmers in the same UVB exposed mouse skin, indicating selective inhibition of oxidative DNA damage by genistein. Induction of H2O2was independent of UVB fluences whereas the levels of MDA and 8-OHdG were induced in an UVB fluence-dependent manner. The results suggest that H2O2be generated as an acute cutaneous response to UVB irradiation, while MDA and 8-OHdG are accumulated with increasing UVB exposure and more closely related to chronic effects of UVB radiation. Pre-treatment of animals with 10 μmol of genistein 1 h prior to UVB exposure significantly inhibited UVB-induced H2O2and MDA in skin and 8-OHdG in epidermis as well as internal organs. Suppression of 8-OHdG formation by genistein has been corroborated in purified DNA irradiated with UVA and B. In summary, our results suggest that UVB irradiation elicit a series of oxidative events, which can be substantially inhibited by isoflavonoid genistein through either direct quenching of reactive oxygen species or indirect antiinflammatory effects. Thus, the antioxidative properties of genistein may explain for the mechanisms of anti-photocarcinogenic action of genistein.