Nephrotoxicity of D-proparglyglycine in mice

Arch Toxicol. 2000 Oct;74(8):473-9. doi: 10.1007/s002040000156.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / metabolism
  • Alkynes / toxicity*
  • Amino Acid Sequence
  • Amino Acids / metabolism
  • Animals
  • D-Amino-Acid Oxidase / antagonists & inhibitors*
  • D-Amino-Acid Oxidase / physiology
  • Enzyme Inhibitors / toxicity*
  • Glycine / analogs & derivatives*
  • Glycine / metabolism
  • Glycine / toxicity
  • Kidney / drug effects*
  • Mice
  • Molecular Sequence Data
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Alkynes
  • Amino Acids
  • Enzyme Inhibitors
  • Tumor Necrosis Factor-alpha
  • propargylglycine
  • D-Amino-Acid Oxidase
  • Glycine