1,2,3,4,6-Penta-O-galloyl-beta-D-glucose reduces renal crystallization and oxidative stress in a hyperoxaluric rat model.
1,2,3,4,6-Penta-O-galloyl-beta-D-glucose reduces renal crystallization and oxidative stress in a hyperoxaluric rat model.
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1,2,3,4,6-PENTA-O-GALLOYL-BETA-D-葡萄糖可在高氧大鼠模型中降低肾脏结晶和氧化应激。
DOI：
10.1038/ki.2010.458
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发表时间：
2011-03
影响因子：
19.6
通讯作者：
Kim SH
中科院分区：
文献类型：
--
作者：
Lee HJ;Jeong SJ;Lee HJ;Lee EO;Bae H;Lieske JC;Kim SH
草酸钙（CaOx）晶体与肾细胞的粘附可能是与显著高尿酸相关的肾结石发病机制中的关键事件。先前，我们发现从传统草药中分离的1，2，3，4，6-五-O-没食子酰基-β-D-葡萄糖（PGG）通过作用于细胞以及晶体表面来减少CaOx晶体对肾上皮细胞的粘附。在这里，我们使用的乙二醇（EG）介导的高尿酸大鼠模型，发现氧化应激的证据表明，肾脏抗氧化酶超氧化物歧化酶，过氧化氢酶，谷胱甘肽过氧化物酶的活性降低，肾细胞凋亡和血清丙二醛水平增加，所有明显的21天的EG治疗。这些高尿酸的影响被逆转的同时PGG治疗沿着降低尿草酸水平和CaOx过饱和。肾上皮细胞表达的晶体结合分子透明质酸弥漫性增加7天内EG启动，这表明它不是一个结果，但之前的晶体沉积。肾细胞骨桥蛋白（OPN）也上调，在EG治疗的动物，PGG显着减弱OPN和透明质酸的过度表达。因此，我们的研究结果表明，PGG减少肾结晶和氧化肾细胞损伤，并可能是一个候选的化学预防剂肾结石。
Adhesion of calcium oxalate (CaOx) crystals to kidney cells may be a key event in the pathogenesis of kidney stones associated with marked hyperoxaluria. Previously, we found that 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG), isolated from a traditional medicinal herb, reduced CaOx crystal adhesion to renal epithelial cells by acting on the cells as well as the crystal surface. Here we used the ethylene glycol (EG) - mediated hyperoxaluric rat model and found evidence of oxidant stress as indicated by decreases in the activities of the renal antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, with increased kidney cell apoptosis and serum malondialdehyde levels, all evident by 21 days of EG treatment. These effects of hyperoxaluria were reversed by concurrent PGG treatment along with decreased urinary oxalate levels and CaOx supersaturation. Renal epithelial cell expression of the crystal binding molecule hyaluronan increased diffusely within 7 days of EG initiation, suggesting it is not a result of but precedes crystal deposition. Renal cell osteopontin (OPN) was also up regulated in EG-treated animals, and PGG significantly attenuated over expression of both OPN and hyaluronan. Thus, our findings demonstrate that PGG reduces renal crystallization and oxidative renal cell injury, and may be a candidate chemo preventative agent for nephrolithiasis.