Germanium, Tin and Arsenic in Rats: Effects on growth, survival, pathological lesions and life span

Chronic renal failure developed in 5 patients who were taking germanium dioxide (GeO₂)-containing compounds. Renal functional deterioration was slow but progressive and dialysis treatment was necessitated temporarily in 2 patients. After the discontinuation of GeO₂, the impaired renal function tended to improve but remained abnormal for an observation period of 10–40 months. The lack of proteinuria and hematuria was characterized as the clinical manifestations. Renal biopsy specimens revealed the tubular epithelial cell degeneration containing hematoxylin-positive fine granules on light microscopy, and electron-dense inclusions in the swollen mitochondria on electron microscopy. These findings localized mainly in distal segment of the tubules. In the rats given GeO₂ orally for 10 weeks, similar histological lesions were evident, as manifested by marked weight loss, anemia, azotemia, and negative proteinuria. In the rats given carboxyethylgermanium sesquioxide, these changes were not observed and Ge concentration of kidney was significantly lower than in the rats given GeO₂. The present study indicates that chronic GeO₂ intake causes progressive renal dysfunction characterized by the degeneration of distal tubules.

Section: Discussionsupporting

confidence: 85%

Germanium Dioxide-Induced Nephropathy: A New Type of Renal Disease

Sanai

Okuda

Onoyama

et al. 1990

“…It is known that Ge is eliminated through the kidney [21,22], Schroeder et al [23] demonstrated that the Ge content was increased in the kidney in Ge-fed rats. In a human autopsied case of long-term G e 0 2 intake, Ge-rich depositions were demonstrated in the kidney and other organs including spleen, thyroid gland, psoas muscle, and jejunum and others [20], The present study revealed that the incidence of histological abnormalities of the kidney was related with the renal-tissue concentration and the urinary excretion of Ge, which increased in proportion to the administered dose of G e 0 2.…”

Section: Discussionmentioning

confidence: 99%

Dose Dependency of Germanium-Dioxide-Induced Nephrotoxicity in Rats

Sanai

Onoyama

Osato

et al. 1991

The dose dependency of germanium dioxide(GeO₂)-induced nephrotoxicity was investigated experimentally in rat groups orally treated with high (150 mg/kg/day), moderate (75 mg/kg/day), or low (37.5 mg/kg/day) doses of GeO₂, and in an untreated group. Renal dysfunction, indicated by the increase of blood urea nitrogen and the decrease of creatinine clearance, and systemic toxicity by weight loss, anemia, and hypoproteinemia were more apparent in rats treated with the higher dose of GeO₂. Urinalysis including daily urinary protein excretion did not reveal any abnormalities in any of the groups. Urinary excretion and renal-tissue content of Ge were significantly elevated in the group of the higher dose of GeO₂. Light microscopically, vacuolar degeneration and depositions of granules positive for periodic acid-Schiff in distal tubules were predominant in the higher-dose group of GeO₂. The present study demonstrates that GeO₂-induced nephrotoxicity develops dose dependently.

“…Ge-induced renal injury has never been reported except in these Japanese cases. Although Schroeder et al [7] have demonstrated that proteinuria was induced in rats fed Ge and although they concluded that Ge is nephrotoxic, they did not describe any renal pathological changes. More over, it appears that with respect to proteinuria, there is a difference between the Japanese case reports and the results of Schroeder et al [7] in nonhumans: no Japanese case, including our patient showed any abnormality in urinalysis.…”

Section: Discussionmentioning

confidence: 95%

“…Although Schroeder et al [7] have demonstrated that proteinuria was induced in rats fed Ge and although they concluded that Ge is nephrotoxic, they did not describe any renal pathological changes. More over, it appears that with respect to proteinuria, there is a difference between the Japanese case reports and the results of Schroeder et al [7] in nonhumans: no Japanese case, including our patient showed any abnormality in urinalysis. The glomerulis are not thought to be damaged in Ge com pound users, but from the clinical and morphological find ings it seems clear that tubular epithelial cells are the main site of injury.…”

Section: Discussionmentioning

confidence: 95%

“…Ge is also contained in spirogermanium, a newly developed antineoplastic agent [2][3][4], and in other hand, sodium germanate has been demonstrated to be toxic to the liver and kidney [7], and GeCT and water-soluble germanates have a certain degree of toxicity [1]. Several animal experiments underscore the cellular toxicity of Ge compounds [1,7,8].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Nephrotoxicity of Germanium Compounds: Report of a Case and Review of the Literature

Takeuchi

Yoshizawa²,

Oshima³

et al. 1992

A 55-year-old woman was admitted to our hospital, complaining of general malaise, muscular weakness, anorexia and weight loss. She had a history of ingesting of a certain germanium (Ge) compound over the preceding 19 months, with a total dose of 47 g as Ge element. She was found to have renal failure (blood urea nitrogen, 44 mg/dl; serum creatinine, 2.6 mg/dl) without abnormal findings in urinalysis, and muscular and nervous damage. Initially, polymyositis was diagnosed and prednisolone administered. However, no improvement was seen, and neuromuscular symptoms and signs steadily worsened, ending in death. Microscopic study of the kidney showed that lipofuscin granules increased in the cells of the thick ascending limb of Henle’s loop to the distal convoluted tubule accompanying mild tubular atrophy and that some of the tubules of these segments had vacuolar degeneration or desquamation. No apparent glomerular and vascular changes were observed. High Ge content was found in serum, urine and various tissues, e.g., spleen, liver, kidney, adrenal gland and myocardium, while in controls Ge could not be detected in sera, urine or tissues. We also review case reports about Ge toxicity, and discuss the pathogenesis of renal failure induced by Ge compounds.