Katiyar Santosh K
Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294-0019, USA.
Int J Oncol. 2002 Dec;21(6):1213-22.
It is well documented that ultraviolet (UV) light-induced immune suppression and oxidative stress play an important role in the induction of skin cancers. Earlier, we have shown that topical treatment of silymarin, a plant flavonoid from milk thistle (Silybum marianum L. Gaertn.), to mouse skin prevents photocarcinogenesis, but the preventive mechanism of photocarcinogenesis in vivo animal system by silymarin is not well defined and understood. To define the mechanism of prevention, we employed immunostaining, analytical assays and ELISA which revealed that topical treatment of silymarin (1 mg/cm2 skin area) to C3H/HeN mice inhibits UVB (90 mJ/cm2)-induced suppression of contact hypersensitivity (CHS) response to contact sensitizer dinitrofluorobenzene. Prevention of UVB-induced suppression of CHS by silymarin was found to be associated with the inhibition of infiltrating leukocytes, particularly CD11b+ cell type, and myeloperoxidase activity (50-71%). Silymarin treatment also resulted in significant reduction of UVB-induced immunosuppressive cytokine interleukin-10 producing cells and its production (58-72%, p<0.001). Topical treatment of silymarin also resulted in significant reduction of the number of UVB-induced H2O2 producing cells and inducible nitric oxide synthase expressing cells concomitant with decrease in H2O2 (58-65%, p<0.001) and nitric oxide (65-68%, p<0.001) production. Together, these data suggest that prevention of UVB-induced immuno-suppression and oxidative stress by silymarin may be associated with the prevention of photocarcinogenesis in mice. The data obtained from this study also suggest: i) phase-I clinical trial of silymarin in high skin cancer risk human population and ii) development of sunscreen containing silymarin as an antioxidant (chemopreventive agent) or silymarin can be supplemented in skin care products.
紫外线（UV）诱导的免疫抑制和氧化应激在皮肤癌的诱发中起重要作用，这一点已有充分的文献记载。此前，我们已经表明，用来自水飞蓟（水飞蓟属植物）的植物黄酮水飞蓟素局部处理小鼠皮肤可预防光致癌作用，但水飞蓟素在体内动物系统中预防光致癌作用的机制尚未明确。为了确定预防机制，我们采用了免疫染色、分析测定和酶联免疫吸附测定（ELISA），结果显示，对C3H/HeN小鼠皮肤局部给予水飞蓟素（1毫克/平方厘米皮肤面积）可抑制紫外线B（90毫焦/平方厘米）诱导的对接触致敏剂二硝基氟苯的接触性超敏反应（CHS）的抑制。发现水飞蓟素预防紫外线B诱导的CHS抑制与浸润白细胞的抑制有关，特别是CD11b+细胞类型以及髓过氧化物酶活性（50 - 71%）。水飞蓟素处理还导致紫外线B诱导的产生免疫抑制细胞因子白细胞介素 - 10的细胞及其产生量显著减少（58 - 72%，p<0.001）。水飞蓟素的局部处理还导致紫外线B诱导的产生过氧化氢的细胞数量以及诱导型一氧化氮合酶表达细胞数量显著减少，同时过氧化氢（58 - 65%，p<0.001）和一氧化氮（65 - 68%，p<0.001）的产生量也减少。总之，这些数据表明，水飞蓟素预防紫外线B诱导的免疫抑制和氧化应激可能与预防小鼠光致癌作用有关。从这项研究中获得的数据还表明：i）对皮肤癌高风险人群进行水飞蓟素的I期临床试验；ii）开发含有水飞蓟素作为抗氧化剂（化学预防剂）的防晒霜，或者可以在护肤品中添加水飞蓟素。
