D-amino-acid oxidase is involved in D-serine-induced nephrotoxicity

Chem Res Toxicol. 2005 Nov;18(11):1678-82. doi: 10.1021/tx0500326.


D-serine is nephrotoxic in rats. Based on circumstantial evidence, it has been suspected that D-amino-acid oxidase is involved in this nephrotoxicity. Since we found that LEA/SENDAI rats lacked D-amino-acid oxidase, we examined whether this enzyme was associated with D-serine-induced nephrotoxicity using the LEA/SENDAI rats and control F344 rats. When d-propargylglycine, which is known to have a nephrotoxic effect through its metabolism by D-amino-acid oxidase, was injected intraperitoneally into the F344 rats, it caused glucosuria and polyuria. However, injection of d-propargylglycine into LEA/SENDAI rats did not cause any glucosuria or polyuria, indicating that D-amino-acid oxidase is definitely not functional in these rats. D-serine was then injected into the F344 and LEA/SENDAI rats. It caused glucosuria and polyuria in the F344 rats but not in the LEA/SENDAI rats. These results indicate clearly that D-amino-acid oxidase is responsible for the D-serine-induced nephrotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / toxicity
  • Animals
  • D-Amino-Acid Oxidase / physiology*
  • Glycine / analogs & derivatives
  • Glycine / toxicity
  • Glycosuria / chemically induced
  • Kidney / drug effects*
  • Male
  • Rats
  • Rats, Inbred F344
  • Serine / toxicity*
  • Species Specificity


  • Alkynes
  • Serine
  • propargylglycine
  • D-Amino-Acid Oxidase
  • Glycine