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  • Title: Nephrotoxicity of D-proparglyglycine in mice.
    Author: Konno R, Ikeda M, Yamaguchi K, Ueda Y, Niwa A.
    Journal: Arch Toxicol; 2000 Oct; 74(8):473-9. PubMed ID: 11097385.
    Abstract:
    When D-propargylglycine was injected intraperitoneally into mice, polyuria, glycosuria, and aminoaciduria were observed as has been previously reported in rats. The urine of the mice treated with D-propargylglycine contained twice as much protein as that of the control mice. Polyacrylamide gel electrophoresis showed a new protein of approximately 62 kDa in the urine of the D-propargylglycine-treated mice. Protein sequencing revealed that this protein was serum albumin. Since the above-mentioned symptoms suggested dysfunction of the renal proximal tubules, the activity of urinary N-acetyl-beta-D-glucosaminidase, a marker enzyme of injury to the proximal tubules, was measured. The urinary enzyme activity was 2.6 times higher in the D-propargylglycine-treated mice than in the control mice. Light- and electron-microscopy showed degenerative and necrotic cells in the straight part of the proximal tubules of the treated mice. However, none of these symptoms was observed in D-propargylglycine-treated mutant mice, lacking D-amino-acid oxidase. These results indicate that D-propargylglycine itself is not nephrotoxic but its metabolite produced by the D-amino-acid oxidase reaction is nephrotoxic and injures proximal tubular cells, resulting in an impairment of the reabsorption of water, glucose, amino acids, and proteins.
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