대한약침학회지 (Journal of Pharmacopuncture)

  • 제12권3호
  • /
  • Pages.5-24
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  • 2009
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  • 2093-6966(pISSN)
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  • 2234-6856(eISSN)
대한약침학회 (KOREAN PHARMACOPUNCTURE INSTITUTE)
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인진호탕(茵蔯蒿湯) 추출액이 Diethylnitrosamine과 CCl4로 유발된 흰쥐의 간암(肝癌) 형성과 간경변(肝硬變)에 미치는 영향

The Effect of Injinho-tang Extract on Hepatocellular Carcinogenesis and Hepatic Cirrhosis Induced by Diethylnitrosamine and CCl4 in Rats

  • 이종범 (원광대학교 한의과대학 내과학교실) ;
  • 허래경 (원광대학교 한의과대학 내과학교실) ;
  • 성기문 (원광대학교 한의과대학 내과학교실) ;
  • 문구 (원광대학교 한의과대학 내과학교실) ;
  • 이종덕 (원광대학교 광주병원 영상의학과) ;
  • 원진희 (원광대학교 한의과대학 내과학교실)
  • Lee, Jong-Bum (Department of Oriental Internal Medicine, College of Oriental Medicine, Won-kwang University) ;
  • Heo, Rae-Kyong (Department of Oriental Internal Medicine, College of Oriental Medicine, Won-kwang University) ;
  • Seung, Kee-Moon (Department of Oriental Internal Medicine, College of Oriental Medicine, Won-kwang University) ;
  • Moon, Goo (Department of Oriental Internal Medicine, College of Oriental Medicine, Won-kwang University) ;
  • Lee, Jong-Deok (Department of Radiology, Won-kwang University Hospital) ;
  • Won, Jin-Hee (Department of Oriental Internal Medicine, College of Oriental Medicine, Won-kwang University)
  • 발행 : 2009.09.30
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초록

Injinho-tang(IJ) has been used for the treatment of hepatobiliary diseases. This study was performed to observe the effect of IJ extract on the hepatocellular carcinogenesis and hepatic cirrhosis induced by Diethylnitrosamine(DENA) and $CCl_4$ in Rats. Experimental groups were divided into two ; 8th and 12th week group, and subdivided into four; normal group(Nor), hepatocellular cancer and hepatic cirrhosis inducing control group(Con), and IJ extract 260mg/kg/day(IJA) or 520mg/kg/day(IJB) administered groups to Con. The results obtained are as follows: The body weight was decreased in the Con, IJA and IJB compared with the Nor from the 2nd week to the 12th week. The weight of liver and the weight of liver/100g body weight were decreased significantly in Con, IJA and IJB compared with the Nor. The activities of aspartate aminotransferase(AST) and alanine aminotransferase(ALT) were significantly increased in the Con compared with Nor, but decreased in the IJA and IJB compared with Con from the 8th week group. The activities of alkaline phosphatase(ALP), lactacte dehydrogenase (LDH) and alpha fetoprotein(AFP) were increased significantly in the Con compared with Nor, but decreased in the IJA and IJB compared with Con. The activities of superoxide dismutase(SOD) were decreased in the IJA and IJB compared with Con, but the activities of catalase were increased in the IJA and IJB compared with Con. According to the light and electron microscopical observation, IJA and IJB improved the morphological and histopathological changes of the liver injured by DENA and $CCl_4$. The number of hepatic p53 positive cells was decreased in the IJA and IJB compared with Con. These results suggest that administration of IJ extract suppress or retard DENA and $CCl_4$-induced hepatocelluar carcinogenesis and hepatic cirrhosis in rats.

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참고문헌

  1. Kim DJ. Pharmacologic Therapy of Hepatic Fibrosis. The Korean J of Hepatology. 2001;7:6-11
  2. Anthony PP, Ishak KG, Nayak NC. The morphology of cirrhosis. J. Clin. Pathol. 1977;31:395 https://doi.org/10.1136/jcp.31.5.395
  3. 전국한의과대학 간계내과학 교수. 간계내과학. 서울. 동약의학연구원. 1989:254-74
  4. Park MD, Choi DY. Bibliographic Study on The Treatment of Liver Cancer. Korean J Oriental Medical Pathology. 1996;10(2):18-27
  5. 장기. 중경전서. 서울. 한림사. 1975:228-37
  6. Heo SK, Yun HJ, Yi HS, Kim CH, Kim, BW, Park SD. Anti-inflammatory Effect of Injinhotang in RAW 264.7 Cells. Korean J of herbology. 2008;23(2):168-78
  7. Lee SW, Han SW, Park CG. Effects of oral administration and herbal drug-acupuncture with Injinhotang on serum levels of GOT, GPT, LDH, ALP and total bililubin in damaged rat Liver induced by the Carbon Tetrachloride (CCl4). The J of Korean Acupuncture & Moxibustion Society). 1999;16(1):351-63
  8. Yun HJ, Kim BW, Lee CH, Jung JH, Heo SK, Park WH, Park SD. Herbal medicine In-Jin- Ho-Tang as a potential anti-cancer drug by induction of apoptosis in human hepatoma HepG2 cells . The J of herbology. 2007;22(3):27-31
  9. 허준. 동의보감(잡병편 상). 서울. 신우문화사. 2004:290
  10. Reitman S, Frankel AS. A colorimetric method for the determination of serum glutamic oxaloacetic and glutamic pyruvic transaminases. Am J Clin Pathol. 1957;28:56-63 https://doi.org/10.1093/ajcp/28.1.56
  11. Lee H-S, Chung YH, Kim CY. Specificities of serum alpha-fetoprotein in HBsAg+and HBs Ag-patients in the diagnosis of hepatocellular carcinoma. Hepatology. 1991;14:68-72 https://doi.org/10.1002/hep.1840140112
  12. Sato Y, Nakata K, Kato Y, et al. Early recognition of hepatocellular carcinoma based on altered profiles of alpha-fetoprotein. N Engl J Med. 1993;328:1802-6 https://doi.org/10.1056/NEJM199306243282502
  13. Beers RF Jr, Sizer IW. A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J Biol Chem. 1952;195(1):133-40
  14. Choi JH, Kang BK. Effects of Guwarujigaktang and Seungbalrijintang on the liver fibrosis induced by Bile Duct Ligation and Dimethylnitrosamine. The Korean Society of Oriental Medical Pathology. 1997;11(2):92-100
  15. Wang YS. Chinese Pharmacology therapeutics. Beijing. Inminwisaeng Publishing Co. 1983:67, 757, 933
  16. Kim HC. Korean Medicinal herbs Pharmacology. Seoul. Jipmoondang Publishing Co. 2004:125-7, 174-7, 239-41
  17. Fontaniere and R Daoust. Histochemical studies on nuclease activity and neoplastic transformation in rat liver during diethylnitrosamine carsinogenesis. Cancer Res. 1973;33:3108-11
  18. Emmilot P and Scherer E. The first relevant cell stage in rat liver carcinogenesis. a quantitative approach. Biochim Biophys Acta. 1980;605:247
  19. Lynne Verana, John Whysner and Gary M. Williams. N-Nitrosodiethy lanmine mechanistic data and risk assessment:Bioactivation, DNA-adduct formation, mutagenicity, and tumor initiation. Pharmacol. Ther. 1996;71:57-81 https://doi.org/10.1016/0163-7258(96)00062-9
  20. Wang PY, Kaneko T, Wang Y, and Sato A. Acarbose alone or in combination with ethanol potentiates the hepatotoxicity of carbon tetrachloride and acetaminophen in rats. Hepatology 1999;29(1):161-5 https://doi.org/10.1002/hep.510290109
  21. Groot H. and Noll T. The crucial role of oxygen partial pressures in haloalkane free radical mediated lipid peroxidation. Biochem. Pharmacol. 1986;35:15 https://doi.org/10.1016/0006-2952(86)90546-0
  22. Zalatnai A, Lapis K. Diethylnitrosamine hepatocarcinogenesis in cirrhotic rats. Acta Morphol Hung. 1987;35(3):211-8
  23. Espandiari P, Robertson LW, Srinivasan C, Glauert HP. Comparison of different initiation protocols in the resistant hepatocyte model. Toxicology. 2005;206(3):373-81 https://doi.org/10.1016/j.tox.2004.07.014
  24. Lucienne Lagopoulos, Geoffrey I Sunahara, and Roland Stalder. The effects of alternating dietary restriction and ad libitum feeding of mice on the development of diethylnitrosamene- induced liver tumors and its correlation to insulinaemia. Carcinogenesis. 1991;12:311-5 https://doi.org/10.1093/carcin/12.2.311
  25. Castro JA, Cignoli EV, Castro CR, Fenos OM. Prevention by cytamine of liver necrosis and early biochemical alteration induced by carbon tetrachloride. Biochem. Pharmacol. 1972;21:49-57 https://doi.org/10.1016/0006-2952(72)90249-3
  26. Honma T, Suda M. Changes in plasma lipoproteins as toxicity markers for carbon tetrachloride. chloroform and dihloromethane. Ind. Health. 1997;35: 519-31 https://doi.org/10.2486/indhealth.35.519
  27. Chenoweth MB and Hake CL. The smaller halogenated aliphatic hydrocarbons. Ann. Rev. Pharmac. 1962;2:363-98 https://doi.org/10.1146/annurev.pa.02.040162.002051
  28. Reitman S and Frankel S. A colorimatric method for determination of serum glutamic oxaloacetic and glutamic pyruvic transaminases. Am. J. Clin. Pathol. 1957;28:58-63
  29. Melen K, Hultberg B, Hagerstrand I, Isaksson A, Joelsson B, Bengmark S. Lysosomal enzymes in plasma, liver and spleen from rats with carbon tetrachloride-induced liver cirrhosis. Enzyme. 1985;33(2):84-8 https://doi.org/10.1159/000469411
  30. Henry RJ, Cannon DC, Winkelman JW. Clinical chemistry principles and techniques. New York. Harper and Row. 1974;2:829
  31. Johnson PJ. The role of serum alpha-fetoprotein estimation in the diagnosis and management of hepatocellular carcinoma. Clin Liver Dis. 2001;5:1450-9 https://doi.org/10.1016/S1089-3261(05)70158-6
  32. Sould AK, Tacka KA, Galvan KA and Penefsky HS. Immediate effects of anticancer drugs on mitochondrial oxygen consumption. Biochem. Phaemacol. 2003;66:977-87 https://doi.org/10.1016/S0006-2952(03)00418-0
  33. Asayama K, Janco RL and Burr IM. Selective induction of manganous superoxide dimutase in human monocytes. Am. J. Physiol. 1985;249:393-7 https://doi.org/10.1152/ajpcell.1985.249.5.C393
  34. Gagandeep S, Rajvanshi P, Sokhi RP, Slehria S, Palestro CJ, Bhargava KK and Gupta S. Transplanted hepatocytes engraft, survive and proliferate in the liver of rats with carbon tetrachloride- induced cirrhosis. J Pathol. 2000;191:78-85 https://doi.org/10.1002/(SICI)1096-9896(200005)191:1<78::AID-PATH587>3.0.CO;2-P
  35. Lane DP. Cancer. p53 guardian of genome. Nature. 1992;358:15-6 https://doi.org/10.1038/358015a0
  36. Burk, RF, Lane JM, and Patel K. Relationship of oxygen and glutathione in protection against carbon tetrachloride-induced hepatic microsomal lipid peroxidation and caovalent binding in the rat. J. Clin Invest. 1984;74 :1996-2001 https://doi.org/10.1172/JCI111621
  37. Yun TK. Effect of Ribounulease on Liver Damage Induced by Carbon Tetrachloride in Rats. Seoul University J. 1963;14:27-48