Quercetin inhibits radiation-induced skin fibrosis.
Quercetin inhibits radiation-induced skin fibrosis.
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DOI：
10.1667/rr3237.1
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发表时间：
2013-08
影响因子：
3.4
通讯作者：
Citrin D
中科院分区：
文献类型：
--
作者：
Horton JA;Li F;Chung EJ;Hudak K;White A;Krausz K;Gonzalez F;Citrin D
辐射导致的皮肤纤维化是一种晚期毒性，可能会由于活动范围减少和疼痛而导致功能丧失。目前的研究试图确定口服槲皮素是否可以减轻辐射引起的皮肤损伤。雌性C3H/母鸡饲喂对照饲料或槲皮素配方饲料(1%体重)。小鼠右后腿接受35GyX射线照射，并对其进行连续追踪，以评估急性毒性和后腿伸展情况。收集组织样本，用于评估可溶性胶原和组织细胞因子。对人和小鼠成纤维细胞进行克隆形成试验，以确定槲皮素对辐射反应的影响。用胶原收缩试验评价成纤维细胞在有或无槲皮素和转化生长因子-β(转化生长因子-β)作用下的收缩能力。Western blotting检测与成纤维细胞收缩和转化生长因子-β信号转导有关的蛋白。治疗组大鼠后肢肌挛缩、胶原沉积及转化生长因子-β的表达均显著低于对照组。Quercetin对成纤维细胞或小鼠肿瘤的放射反应无影响，但可降低成纤维细胞对转化生长因子-β的收缩能力，这一作用与部分稳定磷酸化的Cofilin有关。槲皮素具有减轻放射性皮肤纤维化的作用，应进一步探索其作为放射性纤维化的治疗方法。
Radiation induced fibrosis of the skin is a late toxicity that may result in loss of function due to reduced range of motion and pain. The current study sought to determine if oral delivery of quercetin mitigates radiation-induced cutaneous injury. Female C3H/HeN mice were fed control chow or quercetin-formulated chow (1% by weight). The right hind leg was exposed to 35 Gy of X rays and the mice were followed serially to assess acute toxicity and hind leg extension. Tissue samples were collected for assessment of soluble collagen and tissue cytokines. Human and murine fibroblasts were subjected to clonogenic assays to determine the effects of quercetin on radiation response. Contractility of fibroblasts was assessed with a collagen contraction assay in the presence or absence of quercetin and transforming growth factor-β (TGF-β). Western blotting of proteins involved in fibroblast contractility and TGF-β signaling were performed. Quercetin treatment significantly reduced hind limb contracture, collagen accumulation and expression of TGF-β in irradiated skin. Quercetin had no effect on the radioresponse of fibroblasts or murine tumors, but was capable of reducing the contractility of fibroblasts in response to TGF-β, an effect that correlated with partial stabilization of phosphorylated cofilin. Quercetin is capable of mitigating radiation induced skin fibrosis and should be further explored as a therapy for radiation fibrosis.