Study on the Effect of the Long Term Administration of Germanium (IV) Oxide on Rat Kidney.

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In this study, we investigated the chronic nephrotoxicity of germanium (IV) oxide (GeO_2) in rat and the preventive effects of drugs (enalapril and L-arginine) on the progression of GeO_2 indced nephropathy. Twenty female Wistar rats were fed a standard rat chow containing 1500ppm GeO_2 for 5 months (GeO_2 group). Ten control rats were fed a standard rat chow. At the end of month 4, two rats in the GeO_2 group and one control rat were killed and confirmed the induction of tubulointerstitial nephritis by light microscopy. Then each group was divided into 3 groups. One group was given tap water without a change. Other two groups were administered 50ppm enalapril or 1% L-agrinine solution as a drinking water for last 3 weeks of the experimental period. Rats given GeO_2 had significantly lower weight and significantly higher BUN than rats not given GeO_2. By light microscopic examination, expansion of renal interstitium caused by degeneration and necrosis of tubular epithelium was observed in all rats given GeO_2. Infiltration by inflammatory cells in interstitium was also evident in the GeO_2 group. Rats in the GeO_2 group given tap water was observed the accumulation of the ED1 positive cells (macrophage) and the increased expression of the extracellular matrices (collagen typeIV and fibronectin) in interstitium by immunohistochemistry. Administration of L-arginine for 3 weeks markedly decreased the accumulation of the ED1 positive cells and the expression of the extracellular matrices in renal interstitium of GeO_2 rats compared with similar rats given tap water. But enalapril had little effect on those changes. Relative expression levels of collagen typeIV mRNA in kidney were measred by RT-PCR.The levels of mRNA correlated with that of collagen typeIV.The increase of the mRNA level in rats given GeO_2 was suppressed by the administration of L-arginine significantly.