germanium and Kidney-Diseases

Ginseng preparations contain high concentrations of germanium (Ge), which was reported to contribute to diuretic resistance or renal failure. However, Ge content in ginseng and the influence on renal functions remain unclear. Forty rats were randomly divided into control group, low, moderate, and high Ge ginseng-treated group and observed for 25 days. Daily urine, renal functions, and serum and urine electrolytics were measured. Ge retention in the organs and renal histological changes were also evaluated. Ge content ranged from 0.007 to 0.450 µg/g in various ginseng samples. Four groups showed no difference in the daily urine output, glomerular filtration rate, urinary electrolytes excretions, 24 h-urine protein, as well as plasma and urine urea nitrogen, creatinine, osmotic pressure, and pH values. Ge did not cause any renal pathological effects in this study. No Na and water retention was detected in the ginseng-treated groups. Ge retention in various organs was found highest in spleen, followed by the kidney, liver, lung, stomach, heart, and pancreas. The total Ge contents in various ginsengs were low, and ginseng treatment did not affect renal functions or cause renal histological changes.

Topics: Animals; Creatinine; Diuretics; Electrolytes; Germanium; Glomerular Filtration Rate; Heart Failure; Hydrogen-Ion Concentration; Kidney; Kidney Diseases; Male; Panax; Random Allocation; Rats; Rats, Sprague-Dawley; Sodium; Urinalysis

Long-term oral ingestion of germanium dioxide (GeO2) causes progressive renal failure derived from tubulointerstitial nephropathy in humans and animals. The characteristic of GeO2-induced nephropathy is the renal tissue injury persisting for a long time, even after cessation of GeO2 ingestion. However, a treatment that can suppress the long-lasting renal tissue injury has not yet been established.. Using the methods of immunohistochemistry and reverse transcription-polymerase chain reaction, we examined the expression of ED1-positive cells (macrophages/monocytes), transforming growth factor (TGF)-beta1 mRNA and protein and collagen type IV mRNA and protein in the kidneys of rats with GeO2-induced nephropathy. Concomitantly, the effects of L-arginine treatment on their expression was explored in the kidneys of rats with GeO2-induced nephropathy.. Chronic administration of GeO2 caused tubulointerstitial nephropathy characterized by leukocyte invasion into the enlarged tubulointerstitial space in rats. The expression of ED1-positive cells, TGF-beta1 protein and collagen type IV protein was markedly increased in the tubulointerstitium of the renal cortex from rats with GeO2-induced nephropathy. Similarly, TGF-beta1 and collagen type IV mRNA were significantly enhanced in the renal cortex of rats with GeO2-induced nephropathy. A small number of tubulointerstitial cells expressing TGF-beta1 protein were also observed in the renal cortex of rats with GeO2-induced nephropathy. However, L-arginine treatment led to a parallel decrease in the expression of ED1-positive cells, TGF-beta1 mRNA and collagen type IV mRNA and protein in rats with GeO2-induced nephropathy.. In general, collagen synthesis is driven by TGF-beta1 in the fibrotic process associated with a variety of renal disorders. TGF-beta1 is secreted by TGF-beta1 producing cells such as macrophages, fibroblasts and myofibroblasts. Thus, the present study indicates that the expression of collagen type IV may be mediated by TGF-beta1 released from invading macrophages and, to a lesser extent, released from tubulointerstitial cells, presumably fibroblasts and/or myofibroblasts in GeO2-induced nephropathy. L-Arginine treatment inhibits collagen type IV synthesis possibly by suppressing macrophage invasion and the resultant TGF-beta1 expression in this nephropathy. L-Arginine treatment may be beneficial in the prevention of tubulointerstitial fibrosis, which is considered to be the terminal stage of GeO2-induced nephropathy.

Topics: Animals; Arginine; Collagen; Female; Germanium; Kidney; Kidney Diseases; Kidney Tubules; Macrophages; Monocytes; Rats; Rats, Wistar; RNA, Messenger; Transforming Growth Factor beta

Topics: Germanium; Humans; Kidney; Kidney Diseases; Kidney Failure, Chronic; Male; Middle Aged; Peripheral Nervous System Diseases

Sensory ataxia in inorganic germanium intoxication is rare. A 63-year-old housewife had taken inorganic germanium preparations at a dosage of 36 mg a day for about 6 years (total dose about 80 g). She subsequently developed difficulty in writing and gait disturbance with peripheral neuropathy and renal involvement. Germanium, which is not usually detected in the non-germanium user, was accumulated in her hair and nails, permitting a diagnosis of inorganic germanium intoxication. The peripheral neuropathy and renal injury were not reversible after discontinuing the preparation. Pneumonia and sepsis then supervened and the patient died. Autopsy findings showed degeneration and loss of the dorsal root ganglion cells and degeneration of the dorsal column of the spinal cord. Two previously reported cases presented with ataxia. These patients took germanium for long periods and/or large quantities like our case. It was supposed that sensory ataxia was induced by chronic and dose dependent toxicity of inorganic germanium.

Topics: Aged; Ataxia; Brain; Female; Ganglia; Germanium; Humans; Kidney Diseases; Magnetic Resonance Imaging; Motor Neurons; Nerve Degeneration; Neural Conduction; Spinal Cord

A histopathological study was performed to examine the influence of propagermanium and germanium dioxide (GeO2) on chemically induced renal lesions in rats. Animals were treated with adriamycin or mercuric chloride to induce glomerular or proximal tubular damage, and then given drinking water containing propagermanium (480 or 2,400 ppm solution) or GeO2 (300 or 1,500 ppm solution: equivalent to propagermanium in terms of germanium contents). The distal tubular epithelium after 8 weeks dosage with the 1,500 ppm solution of GeO2 was characterized by vacuolization and deposits of PAS-positive material not only in adriamycin-treated rats, but also in normal rats. In contrast, propagermanium administration was not associated with any alternation in the changes induced by adriamycin or mercuric chloride. We previously clarified that propagermanium had no biochemical influence on the renal function of these renal injured rats. The histological demonstration that this compound does not exert renal toxicity, even when given at a high dosage to renal injured rats, further indicates that it would not exacerbate renal dysfunction already present. This confirms that propagermanium may be a safe compound for use in individuals with compromised kidneys.

Topics: Animals; Doxorubicin; Epithelium; Germanium; Kidney Diseases; Kidney Tubules, Distal; Male; Mercuric Chloride; Organometallic Compounds; Propionates; Rats; Rats, Wistar

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.

Topics: Animals; Electron Probe Microanalysis; Female; Germanium; Kidney Diseases; Kidney Tubules; Microscopy, Electron; Organometallic Compounds; Propionates; Rats; Rats, Inbred Strains; Tissue Distribution

Topics: Adolescent; Follow-Up Studies; Food, Fortified; Germanium; Humans; Kidney; Kidney Diseases; Male

Topics: Adult; Aged; Carbon Tetrachloride; Female; Germanium; Hemolytic-Uremic Syndrome; Humans; Kidney Diseases; Male; Mefenamic Acid; Middle Aged; Mitomycin; Mitomycins; Penicillamine

Inductively coupled atomic emission spectrometry was used for the determination of germanium in hair, nail, and toenail. The levels of germanium in three individuals administered a high concentration of a germanium preparation daily for about 12-16 months were very high: 56.4-173.7; 5.4-35.0; and 14.0-15.8 micrograms g-1 in hair, nail, and toenail, respectively. The levels for normal or unexposed persons are very low and were not detected by the method.

Topics: Adult; Environmental Exposure; Female; Foot; Germanium; Hair; Hand; Humans; Kidney Diseases; Male; Muscular Diseases; Nails; Reference Values; Spectrum Analysis

In a phase I study of spirogermanium, a new azaspiran-germanium compound, 28 patients were given a multiple-dose schedule. When infused over 1 hour, the maximum tolerated single dose of this agent was greater than 120 mg/m2 but significant chronic neurologic toxicity occurred after 1-2 weeks of treatment. Patients with a poor performance status (PS) were the most likely to manifest toxic reactions. Suggested phage II dose levels for infusion treatment with spirogermanium are 120 mg/m2 for patients with a PS of 0-2 and 80 mg/m2 for patients with a PS of 3.

Topics: Adult; Aged; Antineoplastic Agents; Drug Administration Schedule; Drug Evaluation; Female; Germanium; Humans; Kidney Diseases; Male; Middle Aged; Organometallic Compounds; Spiro Compounds