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二氧化锗在实验动物中的亚急性肾毒性

Subacute nephrotoxicity of germanium dioxide in the experimental animal.

作者信息

Sanai T, Oochi N, Okuda S, Osato S, Kiyama S, Komota T, Onoyama K, Fujishima M

机构信息

Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.

出版信息

Toxicol Appl Pharmacol. 1990 Apr;103(2):345-53. doi: 10.1016/0041-008x(90)90234-l.

Abstract

Germanium (Ge; atomic number 32, atomic weight 72.6) belongs to IVb group of the Periodic Table and is found as a trace metal in soil, rocks, plants, and animals. It is widely used in industry because of its semiconductive nature. Some biological activities have been shown in Ge derivatives. Recently, patients with persistent renal damage after chronic ingestion of germanium dioxide (GeO2)-containing compounds have been reported in Japan. This study aimed to investigate subacute nephrotoxicity of GeO2 in Lewis male rats. The rats were treated orally with GeO2 for 13 weeks (GeO2 group) and were compared with those treated with GeO2 for only the first 4 weeks (GeO2-4-week group) and with untreated controls. Renal dysfunction was demonstrated by the increased serum creatinine, BUN, and serum phosphate and decreased creatinine clearance. Liver dysfunction was observed as demonstrated by the increased GOT and GPT, and hypoproteinemia by the decreased total protein and albumin in the GeO2 group. However, daily urinary protein excretion or urinalysis did not differ among the groups. Kidney weight and Ge content of tissues were significantly elevated in the GeO2 group. With the light microscope, vacuoles and the depositions of PAS-stained particles, which correspond to electron-microscopic dense granules in the swollen mitochondria, were predominantly observed in distal tubular epithelium in the GeO2 group. Even in the GeO2-4-week group of rats, serum creatinine was increased and the above-mentioned histological abnormalities were observed, but were less intense.

摘要

锗(Ge;原子序数32,原子量72.6)属于元素周期表的IVb族,在土壤、岩石、植物和动物中作为痕量金属存在。由于其半导体性质,它在工业中被广泛使用。锗衍生物已显示出一些生物活性。最近,日本报道了慢性摄入含二氧化锗(GeO2)化合物后出现持续性肾损伤的患者。本研究旨在调查GeO2对雄性Lewis大鼠的亚急性肾毒性。大鼠口服GeO2 13周(GeO2组),并与仅在最初4周接受GeO2治疗的大鼠(GeO2 - 4周组)和未治疗的对照组进行比较。血清肌酐、尿素氮和血清磷酸盐升高以及肌酐清除率降低表明存在肾功能障碍。GeO2组中谷丙转氨酶(GOT)和谷草转氨酶(GPT)升高表明存在肝功能障碍,总蛋白和白蛋白降低表明存在低蛋白血症。然而,各组间每日尿蛋白排泄量或尿液分析无差异。GeO2组的肾脏重量和组织中的锗含量显著升高。光学显微镜下,GeO2组在远端肾小管上皮中主要观察到空泡以及PAS染色颗粒的沉积,这些颗粒对应于肿胀线粒体中的电子显微镜致密颗粒。即使在GeO2 - 4周组大鼠中,血清肌酐也升高,并且观察到上述组织学异常,但程度较轻。

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