D-amino-acid oxidase is involved in D-serine-induced nephrotoxicity.
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.
Maekawa
Masao
M
Department of Physiology and Biological Information, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan. maekawa@dokkyomed.ac.jp
Okamura
Tadashi
T
Kasai
Noriyuki
N
Hori
Yuuichi
Y
Summer
Karl H
KH
Konno
Ryuichi
R
D000480:Alkynes / Q000633:toxicity; D000818:Animals; D003605:D-Amino-Acid Oxidase / Q000502:physiology*; D005998:Glycine / Q000031:analogs & derivatives / Q000633:toxicity; D006029:Glycosuria / Q000139:chemically induced; D007668:Kidney / Q000187:drug effects*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012694:Serine / Q000633:toxicity*; D013045:Species Specificity
D000480:Alkynes; D012694:Serine; C009055:propargylglycine; D003605:D-Amino-Acid Oxidase; D005998:Glycine