Sanai T, Okuda S, Onoyama K, Oochi N, Takaichi S, Mizuhira V, Fujishima M
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Kidney Int. 1991 Nov;40(5):882-90. doi: 10.1038/ki.1991.289.
Chronic nephrotoxicity was investigated in rats orally administered germanium dioxide (GeO2) and carboxyethylgermanium sesquioxide (Ge-132) for 24 weeks. Increased BUN and serum phosphate as well as decreased creatinine clearance, weight loss, anemia and liver dysfunction were apparent at week 24 only in the GeO2 treated group. Vacuolar degeneration and granular depositions were observed by light microscope in the degenerated renal distal tubules in the rats of this group, with the semiquantitative scores of tubular degeneration being 95 +/- 9% in the GeO2 group, 3 +/- 1% in the Ge-132 group and 1 +/- 1% in the control group, respectively. Electron microscopy revealed electron-dense inclusions in the swollen mitochondrial matrix of the distal tubular epithelium in the GeO2 group. Although systemic toxicities were reduced after GeO2 was discontinued at week 24, renal tubulointerstitial fibrosis became prominent even at week 40 (16 weeks after discontinuation). A Ge.K alpha X-ray spectrum was clearly demonstrated in the mitochondrial matrix of the distal tubular epithelium in the GeO2 group with the help of electron probe X-ray microanalysis. On the other hand, neither toxic effects nor renal histological abnormalities were manifested in either the Ge-132 or the control group. The renal tissue content of germanium was high at weeks 24 and 40 in the GeO2 group. From these results, it is concluded that GeO2 causes characteristic nephropathy while Ge-132 does not. In addition, it appears that residual GeO2 remains for a considerably long time even after the cessation of GeO2 intake.
通过给大鼠口服二氧化锗（GeO₂）和羧乙基锗倍半氧化物（Ge-132）24周，研究其慢性肾毒性。仅在二氧化锗治疗组中，在第24周时出现血尿素氮和血清磷酸盐升高，同时肌酐清除率降低、体重减轻、贫血和肝功能障碍。该组大鼠的退化肾远端小管经光学显微镜观察可见空泡变性和颗粒沉积，二氧化锗组肾小管变性的半定量评分为95±9%，Ge-132组为3±1%，对照组为1±1%。电子显微镜显示二氧化锗组远端肾小管上皮细胞肿胀的线粒体基质中有电子致密包涵体。尽管在第24周停用二氧化锗后全身毒性降低，但即使在第40周（停药后16周）肾小管间质纤维化仍很明显。借助电子探针X射线微分析，在二氧化锗组远端肾小管上皮细胞的线粒体基质中清楚地显示出Ge.KαX射线光谱。另一方面，Ge-132组和对照组均未表现出毒性作用或肾脏组织学异常。在二氧化锗组中，第24周和第40周时肾脏组织中的锗含量较高。从这些结果可以得出结论，二氧化锗会导致特征性肾病，而Ge-132则不会。此外，即使停止摄入二氧化锗后，似乎仍有相当长一段时间残留有二氧化锗。
