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d-Amino-acid Oxidase Is Involved in d-Serine-Induced Nephrotoxicity

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Department of Physiology and Biological Information and Department of Microbiology, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan, Institute for Animal Experimentation, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Miyagi 980-8575, Japan, and Institute of Toxicology, GSF-National Research Center for Environment and Health, 85758 Neuherberg, Germany
Cite this: Chem. Res. Toxicol. 2005, 18, 11, 1678–1682
Publication Date (Web):October 21, 2005
Copyright © 2005 American Chemical Society

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    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.

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     To whom correspondence should be addressed. Tel:  +81-282-87-2126. Fax:  +81-282-86-2011. E-mail:  [email protected].

     Department of Physiology and Biological Information, Dokkyo University School of Medicine.

     Tohoku University Graduate School of Medicine.


     Present address:  Division of Animal Models, Department of Infectious Diseases, Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.

     GSF-National Research Center for Environment and Health.

     Department of Microbiology, Dokkyo University School of Medicine.

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