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Study on a Single-Dose Toxicity Test of D-Amino Acid Oxidase (DAAO) Extracts Injected into the Tail Vein of Rats

  • Kang, Jungue (Wonkwang University College of Oriental Medicine) ;
  • Lee, Eun-Yong (Department of Acupuncture & Moxibustion Medicine, Semyung University Oriental Medicine Hospital) ;
  • Song, Bong-Keun (Department of Internal Medicine, Wonkwang Gwangju Oriental Medical Hospital) ;
  • Lee, Seung-Deok (Department of Acupuncture & Moxibustion, Dongguk University College of Oriental Medicine) ;
  • Yook, Tae-Han (Department of Acupuncture & Moxibustion, Woosuk University College of Korean Medicine) ;
  • Ahn, Seong-Hun (Department of Meridian & Acupoint, Wonkwang University College) ;
  • Son, Il-Hong (Department of Neurology, Wonkwang University Sanbon Hospital) ;
  • Kim, Sungchul (Department of Acupuncture & Moxibustion, Wonkwang Gwangju Oriental Medical Hospital)
  • Received : 2013.04.15
  • Accepted : 2013.04.23
  • Published : 2013.06.30

Abstract

Objective: This study was performed to analyze the single-dose toxicity of D-amino acid oxidase (DAAO) extracts. Methods: All experiments were conducted at the Korea Testing & Research Institute (KTR), an institution authorized to perform non-clinical studies, under the regulations of Good Laboratory Practice (GLP). Sprague-Dawley rats were chosen for the pilot study. Doses of DAAO extracts, 0.1 to 0.3 cc, were administered to the experimental group, and the same doses of normal saline solution were administered to the control group. This study was conducted under the approval of the Institutional Animal Ethics Committee. Results: In all 4 groups, no deaths occurred, and the $LD_{50}$ of DAAO extracts administered by IV was over 0.3 ml/kg. No significant changes in the weight between the control group and the experimental group were observed. To check for abnormalities in organs and tissues, we used microscopy to examine representative histological sections of each specified organ, the results showed no significant differences in any organs or tissues. Conclusion: The above findings suggest that treatment with D-amino acid oxidase extracts is relatively safe. Further studies on this subject should be conducted to yield more concrete evidence.

Keywords

References

  1. Pollegioni L, Piubelli L, Sacchi S, Pilone MS, Molla G. Physiological functions of D-amino acid oxidases : from yeast to humans. Cell Mol Life Sci. 2007; 64(11):1373-94. https://doi.org/10.1007/s00018-007-6558-4
  2. Ono K, Shishido Y, Park HK, Kawazoe T, Iwana S, Chung SP, et al. Potential pathophysiological role of Damino acid oxidase in schizophrenia: immunohistochemical and in situ hybridization study of the expression in human and rat brain. J Neural Transm. 2009;116(10):1335-47. https://doi.org/10.1007/s00702-009-0289-7
  3. Krebs HA. Metabolism of amino-acids: deamination of amino-acids. Biochem J. 1935;29(7):1620-44. https://doi.org/10.1042/bj0291620
  4. Khoronenkova SV, Tishkov VI. D-amino acid oxidase : physiological role and applications. Biochemistry (Moscow). 2008;73(13):1511-18. https://doi.org/10.1134/S0006297908130105
  5. Tishkov VI, Khoronenkova SV. D-Amino acid oxidase : structure, catalytic mechanism, and practical application. Biochemistry (Moscow). 2005;70(1):40-54. https://doi.org/10.1007/s10541-005-0050-2
  6. Sasabe J, Miyoshi Y, Suzuki M, Mita M, Konno R, Matsuoka M, et al. D-Amino acid oxidase controls motoneuron degeneration through D-serine. Proc Natl Acad Sci USA. 2012;109(2):627-32. https://doi.org/10.1073/pnas.1114639109
  7. Kwon KR, Cho AL, Lee SG. [The study on acute and subacute toxicity and anti-cancer effects of cultivated wild ginseng herbal acupuncture]. Pharmacopuncture. 2003;6(2):7-27. Korean. https://doi.org/10.3831/KPI.2003.6.2.007
  8. Paul P, de Belleroche J. The role of D-amino acids in amyotrophic lateral sclerosis pathogenesis: a review. Amino Acids. 2012;43(5):1823-31. https://doi.org/10.1007/s00726-012-1385-9
  9. D'Aniello A, D'Onofrio G, Pischetola M, D'Aniello G, Vetere A, Petrucelli L, et al. Biological role of D-amino acid oxidase and D-aspartate oxidase. Effects of Damino acids. J Biological Chem. 1993;268(36):26941-9.
  10. Smith SM, Uslaner JM, Hutson PH. The therapeutic potential of D-amino acid oxidase (DAAO) inhibitors. Open Med Chem J. 2010;4:3-9. https://doi.org/10.2174/1874104501004020003
  11. Zhao WJ, Gao ZY, Wei H, Nie HZ, Zhao Q, Zhou XJ, et al. Spinal D-amino acid oxidase contributes to neuropathic pain in rats. J Pharm Exp Ther. 2010;332(1):248-54. https://doi.org/10.1124/jpet.109.158816
  12. Verrall L, Burnet PW, Betts JF, Harrison PJ. The neurobiology of D-amino acid oxidase and its involvement in schizophrenia. Mol Psychiatry. 2010;15(2):122-37. https://doi.org/10.1038/mp.2009.99
  13. Kim YG. [Toxicology]. Paju(Korea): Donghwagisul; 1984. p. 15-18. Korean.
  14. Korea Food & Drug Administration. Korea Food & Drug Administration notification 2005-60 [Internet]. Seoul: Korea Food & Drug Administration; 2005. [cited 2013 March 1]. Available from: http://lawwizice.wordpress.com/. Korean.

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