Protective Effect of Yangguksanwha-tang Metabolized by Liver Homogenate on Hypoxia-reperfusion Induced PC12 Cell Damage

간효소에 의해 대사된 양격산화탕의 저산소/재관류로부터 PC12 세포 보호효과

  • Soh Yunjo (Department of Neuroscience, Graduate School of East-West Medical Science, Kyung Hee University)
  • 소윤조 (경희대학교 동서의학대학원 신경과학교실)
  • Published : 2005.02.01

Abstract

The protective effect of Yangguksanwha-tang (YST) against hypoxia-reperfusion insult was investigated in PC12 cells. To elucidate the mechanism of the protective effect of YST, cell viability, the changes in activities of superoxide dismutase, glutathione peroxidase, catalase, caspase 3 and the production of malondialdehyde were observed after treating PC12 cells with YST which was metabolized by rat liver homogenate. Pretreatment of YST with liver homogenate appeared to increase its protective effect against hypoxia-reperfusion insult. The result showed that YST had the highest protective effect against hypoxia/reperfusion at the dose of $2\;{\mu}g/ml$ in PC12 cells, probably by recovering the redox enzyme activities and MDA to control level.

Keywords

References

  1. Murray, C. J. L. and Lopez, A. D. : Mortality by cause for eight regions of the world global burden of disease study. Lancet 349, 1269 (1997) https://doi.org/10.1016/S0140-6736(05)62894-2
  2. 정철, 김욱년, 김민정, 최석문, 어경윤, 박미영, 하정상, 변영주 : 허혈성 뇌졸중의 재발과 연관된 위험인자. 영남의대학술지 10, 423 (1993)
  3. 김현철, 김세주, 최낙경, 김영신, 이병철, 이병철, 이만홍 : 뇌졸중 후 삶의 질에 관한 추적연구. 신경정신의학 41, 681 (2002)
  4. Fisher, M. and Brott, T. G. : Emerging therapies for acute ischemic stroke: new therapies on trial. Stroke 34(2), 359 (2003) https://doi.org/10.1161/01.STR.0000044952.74952.F7
  5. Chan, P. H. : Role of oxidants in ischemic brain damage. Stroke 27, 1124 (1996) https://doi.org/10.1161/01.STR.27.6.1124
  6. 윤진구, 조기호, 김영석, 이경섭 : 뇌졸중에 관한 임상통계적 연구. 대한한방내과학회지 10(1), 25 (1989)
  7. 김진성, 송일병 : 양격산화탕의 효능에 관한 실험적 연구. 경희한의대 논문집 7, 273 (1984)
  8. 배철환, 조기호, 이원철, 김영석, 배형섭, 이경섭, 구본홍 : 폐쇄성 뇌졸중에 대한 임상적 연구. 경희한의대논문집 10, 665 (1987)
  9. 이기주, 김경요 : 십이미관중탕, 양격산화탕, 형방사백산이 백서의 혈압 및 국소 뇌혈류량에 미치는 영향. 한국전통의학지 9(2), 259 (1999)
  10. 이동원, 이원철 : 지주막하출혈 후 뇌기저동맥벽에 존재하는 면역 양성 신경섬유의 변화에 미치는 양격산화탕의 효과. 한의학연구소논문집 8(1), 117 (1999)
  11. Brandon, E. F., Raap, C. D., Meijerman, I., Beijnen, J. H. and Schellens, J. H. : An update on in vitro test methods in human hepatic drug biotransformation research. Toxicol. Appl. Pharmacol, 189(3), 233 (2003) https://doi.org/10.1016/S0041-008X(03)00128-5
  12. Oyanagui, Y. : Reevaluation of assay methods and establishment of kit for superoxide dismutase activity. Anal. Biochem. 142(2), 290 (1984) https://doi.org/10.1016/0003-2697(84)90467-6
  13. Aebi, H. : Catalase in vitro. Methods Enzymol. 105, 121 (1984) https://doi.org/10.1016/S0076-6879(84)05016-3
  14. Lipton, P. : Ischemic cell death in brain neurons. Physiol. Rev. 79(4), 1431 (1999) https://doi.org/10.1152/physrev.1999.79.4.1431
  15. White, B. C., Sullivan, J. M., DeGracia, D. J., O'Neil, B. J., Neumar, R. W., Grossman, L. I., Rafols, J. A. and Krause, G. S. : Brain ischemia and reperfusion: molecular mechanisms of neuronal injury. J. Neurol. Sci. 179(S1-S2), 1 (2000) https://doi.org/10.1016/S0022-510X(00)00386-5
  16. Jenkins, L. W., Povlishock, J. T., Lewelt, W., Miller, J. D. and Becker, D. P. : The role of postischemic recirculation in the development of ischemic neuronal injury following complete cerebral ischemia. Acta. Neuropathol, 55(3), 205 (1981) https://doi.org/10.1007/BF00691320
  17. Sato, M., Hashimoto, H. and Kosaka, F. : Histological changes of neuronal damage in vegetative dogs induced by 18 minutes of complete global brain ischemia: two-phase damage of Purkinje cells and hippocampal CA1 pyramidal cells. Acta. Neuropathol, 80(5), 527 (1990) https://doi.org/10.1007/BF00294614
  18. Krause, G. S., White, B. C., Aust, S. D., Nayini, N. R. and Kumar, K. : Brain cell death following ischemia and reperfusion: a proposed biochemical sequence. Crit. Care Med. 16(7), 714 (1988) https://doi.org/10.1097/00003246-198807000-00015
  19. Siesjo, B. K. : Pathophysiology and treatment of focal cerebral ischemia. Part I: Pathophysiology. J. Neurosurg. 77(2), 169 (1992) https://doi.org/10.3171/jns.1992.77.2.0169
  20. Schoepp, D. D. and Conn, P. J. : Metabotropic glutamate receptors in brain function and pathology. Trends Pharmacol. Sci. 14(1), 13 (1993) https://doi.org/10.1016/0165-6147(93)90107-U
  21. White, B. C., Sullivan, J. M., DeGracia, D. J., O'Neil, B. J., Neumar, R. W., Grossman, L. I., Rafols, J. A. and Krause, G. S. : Brain ischemia and reperfusion: molecular mechanisms of neuronal injury. J. Neurol. Sci. 179, 1 (2000) https://doi.org/10.1016/S0022-510X(00)00386-5
  22. Graham, S. H. and Chen, J. : Programmed cell death in cerebral ischemia. J Cereb. Blood Flow Metab. 21, 99 (2001) https://doi.org/10.1038/sj.bmt.1701089
  23. Thomas, M. and Jankovic, J. : Neurodegenerative disease and iron storage in the brain. Curr. Opin. Neurol.17(4), 437 (2004) https://doi.org/10.1097/01.wco.0000137534.61244.d1
  24. Bharath, S., Hsu, M., Kaur, D., Rajagopalan, S. and Andersen, J. K. : Glutathione, iron and Parkinson's disease. Biochem. Pharmacol. 64(5-6), 1037 (2002) https://doi.org/10.1016/S0006-2952(02)01220-0
  25. Jenner, P. : Oxidative stress in Parkinson's disease. Ann. Neurol. 53 Suppl 3, S26 (2003) https://doi.org/10.1002/ana.10513
  26. Moos, T. and Morgan, E. H. : The metabolism of neuronal iron and its pathogenic role in neurological disease. Ann. N. Y. Acad. Sci. 1012, 14 (2004) https://doi.org/10.1196/annals.1306.002
  27. Takeuchi, N., Matsumiya, K., Takahashi, Y., Higashino, K. and Tanaka, F. : Thiobarbituric acid reactive substances (TBARS) and lipid metabolism in alpha-tocopherol deficient rats. Exp. Gerontol. 12, 63 (1977) https://doi.org/10.1016/0531-5565(77)90034-1
  28. Kim, Y. D., Sohn, N. W., Kang, C. and Soh, Y. : DNA array reveals altered gene expression in response to focal cerebral ischemia. Brain Res. Bull. 58, 491 (2002) https://doi.org/10.1016/S0361-9230(02)00823-7
  29. Gilgun-Sherki, Y., Rosenbaum, Z., Melamed, E. and Offen, D. : Antioxidant therapy in acute central nervous system injury: current state. Pharmacol. Rev. 54(2), 271 (2002) https://doi.org/10.1124/pr.54.2.271
  30. Pirmohamed, M., Madden, S. and Park, B. K. : Idiosyncratic drug reactions. Metabolic bioactivation as a pathogenic mechanism. Clin. Pharmacokinet. 31, 215 (1996) https://doi.org/10.2165/00003088-199631030-00005
  31. Park, B. K., Kitteringham, N. R., Pirmohamed, M. and Tucker, G. T. : Relevance of induction of human drug?metabolizing enzymes: pharmacological and toxicological implications. Br. J. Clin. Pharmacol. 41(6), 477 (1996) https://doi.org/10.1046/j.1365-2125.1996.03482.x