Glyoxylate induces renal tubular cell injury and microstructural changes in experimental mouse

Glyoxylate induces renal tubular cell injury and microstructural changes in experimental mouse
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DOI:
10.1007/s00240-008-0143-7
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发表时间:
2008-08-01
影响因子:
--
通讯作者:
Kohri, Kenjiro
Kohri, Kenjiro
中科院分区:
其他
文献类型:
--
作者:
Hirose, Masahito;Tozawa, Keiichi;Kohri, Kenjiro

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小鼠体内的晶体形成不能通过乙二醇或乙醇酸盐的给药来诱导。为了阐明这些草酸盐前体在小鼠中的差异的原因,我们通过氧化应激的免疫组织化学染色和显微结构观察来研究肾小管上皮损伤。对C57 BL/6雄性小鼠(8周)每日腹腔内注射生理盐水溶液[10 ml/(kg天)]、乙二醇[(48.3 mmol/(kg天)]、乙醇酸盐[1.31 mmol/(kg天)]和乙醛酸盐[1.35 mmol/(kg天)],持续7天。采用免疫组化法检测超氧化物歧化酶(SOD)和丙二醛(MDA),透射电镜观察肾小管上皮细胞氧化应激和形态学变化。仅在乙醛酸处理的小鼠肾脏中显示SOD降低和MDA增加。透射电镜观察显示乙醛酸处理的小鼠肾脏肾小管细胞线粒体内部结构发生破坏和空泡化,微绒毛密度降低。肾小管细胞的这些变化位于晶体形成区。然而,在其他组中没有检测到这种变化。每种草酸盐前体诱导肾上皮细胞发生不同的氧化应激和微结构变化。提示乙醛酸可诱导小鼠肾上皮细胞损伤和形态学改变,从而导致草酸钙结晶的形成。
Crystal formation in mice could not be induced either by the administration of ethylene glycol or by glycolate. To clarify the reasons for the difference among these oxalate precursors in mice, we studied renal tubular epithelial injury by immunohistochemical staining of oxidative stress and observing microstructures. Daily intra-abdominal injection of saline solution [10 ml/(kg day)], ethylene glycol[(48.3 mmol/(kg day)], glycolate [1.31 mmol/(kg day)], and glyoxylate [1.35 mmol/(kg day)] into C57BL/6 male mice (8 weeks) was performed for 7 days. Immunohistochemical staining of superoxide dismutase (SOD) and malondialdehyde (MDA), and transmission electron microscopy (TEM) of renal tubular epithelial cells were performed to observe oxidative stress and morphological changes, respectively. Decreased SOD and increased MDA were shown only in glyoxylate-treated mouse kidneys. The TEM study with glyoxylate-treated mouse kidneys demonstrated that the internal structure of mitochondria in renal tubular cells underwent destruction and vacuolization, and microvilli density decreased. These changes in renal tubular cells were located in the crystal-forming area. However, such changes were not detected in the other groups. Each precursor of oxalate induces different changes in renal epithelial cells regarding oxidative stress and the microstructural changes. It is suggested that calcium oxalate crystal formation requires cell injury and morphological changes of renal epithelial tubular cells induced by glyoxylate administration in the mouse kidney.