Genistein reduces glycosaminoglycan levels in a mouse model of mucopolysaccharidosis type II
Genistein reduces glycosaminoglycan levels in a mouse model of mucopolysaccharidosis type II
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DOI：
10.1111/j.1476-5381.2009.00565.x
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发表时间：
2010-03-01
影响因子：
7.3
通讯作者：
Scarpa, M.
中科院分区：
文献类型：
--
作者：
Friso, A.;Tomanin, R.;Scarpa, M.
背景和目的：粘多糖病(MPS)是一种溶酶体储存障碍，其原因是特定的溶酶体酶催化糖胺多聚糖(GAG)降解。典型的病理学涉及大多数器官系统，包括大脑，以严重的形式出现。大豆异黄酮染料木素由于在体外可以减少GAG的合成而引起了人们的广泛关注。此外，金雀异黄素能够穿过大鼠的血脑屏障。本研究旨在评价染料木素在体内降低尿液和组织中GAG水平的能力。实验方法：采用艾杜酸-2-硫酸酶基因缺失的小鼠作为MPS II型动物模型，分别给予两种剂量的染料木素，5或25 mg中心点kg~(-1)中心点日-1，连续10或20周。用生化和组织化学方法检测尿和组织中GAG含量。关键结果：金雀异黄素治疗10周后，尿GAG水平下降，中心点kg-1和中心点天-1剂量分别为5 mg和25 mg。在肝、脾、肾和心脏的组织样本中，观察到两种剂量的GAG含量在治疗10周后都有所下降。部分动物经金雀异黄素治疗后，脑内GAG沉积减少。结论与启示：给予金雀异黄素后，MPSII小鼠模型中GAG储存减少。我们的结果将支持将这种植物来源的异黄酮用于治疗MPS的联合治疗方案。
Background and purpose:Mucopolysaccharidoses (MPS) are lysosomal storage disorders resulting from a deficit of specific lysosomal enzymes catalysing glycosaminoglycan (GAG) degradation. The typical pathology involves most of the organ systems, including the brain, in its severe forms. The soy isoflavone genistein has recently attracted considerable attention as it can reduce GAG synthesis in vitro. Furthermore, genistein is able to cross the blood-brain barrier in the rat. The present study was undertaken to assess the ability of genistein to reduce urinary and tissue GAG levels in vivo.Experimental approach:We used mice with genetic deletion of iduronate-2-sulphatase (one of the GAG catabolizing enzymes) which provide a model of MPS type II. Two doses of genistein, 5 or 25 mg center dot kg-1 center dot day-1, were given, in the diet for 10 or 20 weeks. Urinary and tissue GAG content was evaluated by biochemical and histochemical procedures.Key results:Urinary GAG levels were reduced after 10 weeks' treatment with genistein at either 5 or 25 mg center dot kg-1 center dot day-1. In tissue samples from liver, spleen, kidney and heart, a reduction in GAG content was observed with both dosages, after 10 weeks' treatment. Decreased GAG deposits in brain were observed after genistein treatment in some animals.Conclusions and implications:There was decreased GAG storage in the MPSII mouse model following genistein administration. Our results would support the use of this plant-derived isoflavone in a combined therapeutic protocol for treatment of MPS.