Study of Germanium Dioxide : Subcellular Distribution and Chronic Toxicity

二氧化锗的研究：亚细胞分布和慢性毒性

• 批准号: 04670304
• 负责人: YAMAZAKI Nobuyuki
• 金额: $ 1.34万
• 依托单位: University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670304/
• 关键词: Germanium dioxide; Kidney; Distribution; Chronic toxicity; Subcellular fractionation; Urine; ゲルマニウム; 腎機能障害

To clarify the biological effects of germanium dioxide (GeO_2) on kidney, we investigated the subcellular distribution and the chronic toxicity of GeO_2 on rats. The following results were obtained.1. Germanium distribution in the subcellular fractions of rat kidney.A single dose of a GeO_2 was intraperitoneally administered to rats (50mg Ge/kg bw), and the subcellular distribution of GeO_2 in kidney was measured from 30 minutes to 24 hours after dosing. In kidney, GeO_2 showed the highest concentration at 30 minutes, and decreased rapidly. The half life of GeO_2 in the tissue was approximately 10 hours. The reduction of the GeO_2 contents in each subcellular fraction was fast, too. But the relative GeO_2 contents among subcellular fractions changed little by the time after dosing. More than two third of GeO_2 distributed in the cytosolic fractions (Nuclear fr.12-14%, Mitochondrial fr.10-15%, Microsomal fr.2-7%, Cytosolic fr.65-76%). The GeO_2 contents per protein weight were also highest in the cytosolic fractions. At 6 hours, the concentrations of Ge (mug Ge/100mg protein) in nuclear fr.mitochondrial fr., microsomal fr.and cytosolic fr.were 2.32(〕SY.+-.〔)1.08, 2.80(〕SY.+-.〔)1.19, 1.15(〕SY.+-.〔)0.47 and 9.94(〕SY.+-.〔)4.45, respectively.2. Chronic toxicity of GeO_2 on rats.GeO_2 (25mg Ge/kg bw, 5mg Ge/kg bw) or saline (control group) was administered subcutaneously to rats for 13 weeks. No change of general appearance and behavior of animals was observed. First 5 weeks, the body weight gains of GeO_2 groups were less than control group, but tose were not significant. There were the increase of urinary volume and the decrease of osmotic pressure of urine in 25mg groups until 5 weeks. The measurements of urinary pH, protein, glucose, occult blood, beta_2-microglobulin and N-acetyl-beta-D-glucosaminidase appeared no difference among three groups. Administration of GeO_2 for 13 weeks caused the enlargement of heart and kidney.

为了阐明二氧化锗（GeO_2）对大鼠肾脏的生物学作用，研究了其亚细胞分布和慢性毒性。得到了以下结果：锗在大鼠肾亚细胞组织中的分布。大鼠腹腔注射单剂量的GeO_2 (50mg Ge/kg bw)，在给药后30min ~ 24h测量GeO_2在肾脏中的亚细胞分布。肾脏中，GeO_2浓度在30min达到最高，随后迅速下降。GeO_2在组织中的半衰期约为10小时。各亚细胞组分中GeO_2含量的降低速度也较快。但随着时间的推移，亚细胞组分中GeO_2的相对含量变化不大。超过三分之二的GeO_2分布在细胞质部分（核区12-14%，线粒体区10-15%，微粒体区2-7%，细胞质区65-76%）。胞质组分中每蛋白重的GeO_2含量也最高。6 h时，核层、线粒体层、微粒体层和细胞质层中Ge浓度分别为2.32(]SY.+-[)1.08、2.80(]SY.+-[)1.19、1.15(]SY.+-[)0.47和9.94(]SY.+-[)4.45。GeO_2对大鼠的慢性毒性。大鼠皮下注射GeO_2 （25mg Ge/kg bw, 5mg Ge/kg bw）或生理盐水（对照组）13周。观察到动物的总体外观和行为没有变化。前5周，GeO_2组体重增加量低于对照组，但差异不显著。25mg组至第5周尿量增加，尿渗透压降低。尿pH、蛋白、葡萄糖、潜血、β - 2微球蛋白、n -乙酰- β - d -氨基葡萄糖酶等指标在三组间无显著差异。给药13周可引起心脏、肾脏肿大。

项目成果

Wada, O.et al.: "Essentiality and toxicity of trace elements." Jpn.J.Nutr.Assess.10(3). 199-210 (1993)

Wada, O.et al.：“微量元素的必需性和毒性。”

和田 攻: "微量元素の必須性と毒性" 栄養-評価と治療. 10. 199-210 (1993)

Osamu Wada：“微量元素的必需性和毒性”营养-评估和治疗10。199-210（1993）。