랫트의 간 손상에 대한 녹차카테킨의 보호 및 치료효과

Effect of Green Tea Catechin on Acute Hepatotoxicity in Rats

  • 육동연 (충북대학교 약학대학 생물건강산업개발연구센터) ;
  • 이미애 (청주대학교 사회과학대학) ;
  • 윤여표 (충북대학교 약학대학 생물건강산업개발연구센터)
  • Yuk, Dong-Yeon (College of Pharmacy, Research Center for Bioresource and Health, Chungbuk National University) ;
  • Lee, Mi-Yea (College of Social Sciences, Cheongju University) ;
  • Yun, Yeo-Pyo (College of Pharmacy, Research Center for Bioresource and Health, Chungbuk National University)
  • 발행 : 2004.09.01

초록

녹차카테킨은 다양한 생리활성을 지닌 것으로 알려지고 있다. 본 실험에서는 사염화탄소와 갈락토사민으로 유발된 간독성에 대한 녹차카테킨의 간기증보호효과가 연구되었다. 녹차 카테킨(50 mg/kg와 100 mg/kg)은 사염화탄소 (0.5 ml/kg)와 갈락토사민(400 mg/kg)이 투여되기 전 그리고 투여후 3일동안 흰쥐에 경구투여되었고, 간기능지표로 AST와 ALT를 측정하였다. 녹차카테킨(50 mg/kg)은 사염화탄소 처리된 랫드에서 상승된 혈중 AST와 ALT 확성을 전투여군(262${\pm}$11, 80${\pm}$19에서 153${\pm}$22, 55${\pm}$25로)과 후투여군(156${\pm}$40, 105${\pm}$3 에서 106${\pm}$22, 55${\pm}$9로) 모두 감소시켰다. 또한 갈락토사민으로 유도한 경우에도 AST와 ALT 수치는 전투여군(576${\pm}$24, 276${\pm}$68 에서 236${\pm}$13, 115${\pm}$13로)과 후투여군(233${\pm}$54, 137${\pm}$11 에서 119${\pm}$23, 44${\pm}$17로)에서 모두 유의성있게 감소된 결과를 나타내었다. 또한 간 조직학적 검사에서도 사염화탄소와 갈락토사민으로 유도된 간경변을 유의성있게 억제하였다. 이상의 결과로 볼 때 녹차카테킨은 간독성에 의한 병변을 예방 및 치료할 수 있는 신약후보물질로서의 가능성을 시사한다.

Green tea catechin (GTC) is known to have a wide variety of pharmacological activites. In the present study, the effects of GTC on acute hepatotoxicity induced by carbon tetrachloride ($CCl_4$) and galactosamine were examined in rats. Two doses (50 or 100 mg/kg) of GTC were administered to rats orally for 3 days befor or after the induction of hepatotoxicity. A hepatotoxicity was induced by the inpraperitoneal injection of the $CCl_4$ (0.5 ml/kg) or galactosamine (400 mg/kg). GTC(50 mg/kg) reduced the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) level of the $CCl_4$-intoxicated rats in the pre-treatment group (from 262${\pm}$11, 80${\pm}$19 to 153${\pm}$22, 55${\pm}$25), and also in the post-treatment group (from 156${\pm}$40, 105${\pm}$3 to 106${\pm}$22, 55${\pm}$9), respectively. And GTC (50 mg/kg) also reduced the levels of AST and ALT in both pre-treatment (from 576${\pm}$24, 276${\pm}$68 to 236${\pm}$13, 115${\pm}$13) and post-treatment (from 233${\pm}$54, 137${\pm}$11 to 119${\pm}$23, 44${\pm}$17) when induced by galactosamine. GTC also showed the inhibition of pathogenesis of hepatocyte of $CCl_{4^-}$ and galatosamine-intoxicated rat. These results suggest that green tea catechin (GTC) may be useful fur the prevention and therapy of hepatotoxic pathogenesis.

키워드

참고문헌

  1. Campos, R., Garrido, A, Guerra, R. and Valenzuela, A. : Silybin dihemisuccinate protects against glutathione depletion and lipid peroxidation indeced by acetaminophen on rat liver, Planta Medica, 55, 417-419 (1989) https://doi.org/10.1055/s-2006-962055
  2. Martindale. : The extra pharmacopoeia, the Pharmaceutical Press, p. 1613 (1989)
  3. Anton Rietveld and Sheila Wiseman : Antioxidant efffects of tea: Evidence from human clinical trials. J. Nutr., 133, 3285S-3292S (2003) https://doi.org/10.1093/jn/133.10.3285S
  4. Miguez M,P., Anundi I., Sainz-Prado L. A., Lindros K. O.: Hepatoprotective mechanism of silymarin: No evidence for involvement of cytochrome P450 2EI. Chemico-Biological Interactions, 91(1), 51-63 (1994) https://doi.org/10.1016/0009-2797(94)90006-X
  5. Bu-Abbas A, Clifford MN, Walker R. : Marked antimutagenic potential of aqueous green tea extracts: Mechanism of action. Mutagenesis, 9, 325-331 (1994) https://doi.org/10.1093/mutage/9.4.325
  6. Stoner G, D., Mukhtar H. : Polyphenols as cancer chemopreventive agents. J. Cell Biochem., 22(Suppl), 169-180 (1995)
  7. Serafini M., GhiseIli A., Ferro Luzzi A. : In vivo antioxidant effects of green tea and black tea in man. Eur. J. Clin. Nutr., 50, 28-32 (1996)
  8. Uchida S., Ozaki M., Suzuki K., Shikita M. : Radioprotective effects of (-)- epigallocatechin 3-O-gallate (green-tea tannin) in mice. Life Sci., 50, 147-152 (1992) https://doi.org/10.1016/0024-3205(92)90296-2
  9. Saeki Y., Ito Y., Shibata M., Sato Y., Takazoe I., Okuda K. : Antimicrobial action of green tea extract, flavono flavor, copper chlorophyIl against oral bacteria, Bull. Tokyo Dental Coli., 34, 33-37 (1993)
  10. Ikigai H., Nakae T., Hara Y., Shimamura T. : Bactericidal catechins damage the lipid bilayer, Biochim. Biophys. Acta, 1147, 132-136 (1993) https://doi.org/10.1016/0005-2736(93)90323-R
  11. Muramatsu K., Fukuyo M., Hara Y. : Effect of green tea catechins on plasma cholesterol level in cholesterol-fed rats. J. Nutr. Sci. Vitaminol. (Tokyo), 32, 613-622 (1986) https://doi.org/10.3177/jnsv.32.613
  12. Uchida S., Ozaki M., Akashi T., Yamashita K., Niwa M., Taniyarna K. : Effects of (-)-epigallocatechin-3-0-gaIlate (green tea tannin) on the life span of stroke-prone spontaneously hypertensive rats. Clin. Exp. Pharmacol. Physiol., 22, S302-S303 (1995) https://doi.org/10.1111/j.1440-1681.1995.tb02928.x
  13. Yokozawa T., Oura H., Nakagawa H., Sakanaka S., Kim M. : Effects of component of green tea on the proliferation of vascular smooth ceIls, Biosci, Biotechnol. Biochem., 59, 2134-2136 (1995) https://doi.org/10.1271/bbb.59.2134
  14. Yamaguchi Y., Hayashi M., Yamazoe H., Kuntomo M. : Preventive effects of green tea extract on lipid abnormalities in serum, liver and aorta of mice fed an atherogenic diet. Nippon Yakurigaku Zasshi, 97, 329-337 (1991) https://doi.org/10.1254/fpj.97.6_329
  15. Kang W.S., Lim I.H., Yuk D.Y., Chung K.H., Park lB., Yoo H.S Yun Y.P. : Antithrombotic activities of green tea catechins and (-)-epigallocatechin gallate, Thrombosis research, 96(3), 229-237 (1999) https://doi.org/10.1016/S0049-3848(99)00104-8
  16. Plaa, G.L. and Charbonneau, M, : Detection and evaluation of chemically induced liver injury. In Principles and Methods of Toxicology (Hayes, A. w., Ed). pp. 839-870, Raven Press., New York (1994)
  17. Zieve, L., Anderson, w.R. and Dozeman. R. : Hepatic regenerative enzyme activity after diffuse injury with galactosamine: relationship to histologic alterations. J. Lab. Clin. Med., 112, 575-582 (1988)
  18. Decker, K. and Keppler, D. : Galactosamine-induced liver injury. In progress in liver disease. (Popper, H. and Schaffer, F, ed.), vol. 14, p. 183, Grone and Stratton, New York (1973)
  19. Wang, J.E and Wendel, A. : Studies on the hepatotoxicity of galactosamine/endotoxin or galactosamine/TNF in the perfused mouse liver. Biochem. Pharmacol., 39, 267-270 (1990) https://doi.org/10.1016/0006-2952(90)90025-G
  20. El-Mofty, SK., Scrotton, M.C., Serroni, A., Nicolini, C. and Farber, J.L., : Early, reversible plasma membrane injury in galactosamine-induced liver cell death. Am. J. Pathol., 79, 579-595 (1975)
  21. Keppler, D., Lesch, R., Reutter, W. and Decker, K. : Experimental hepatitis induced by D-galactosamine. Exp. Mol. Pathol., 9, 279-290 (1968) https://doi.org/10.1016/0014-4800(68)90042-7
  22. Farber, J.L., Gill, G. and Konishi, Y. : Prevention of galactosamine-induced liver cell necrosis by uridine. Am. J. Pathol., 72, 53-62 (1973).
  23. Iller, E.C. and Miller, J.A. : Hepatocarcinogenesis by chemicals. In Progress in liver disease (Popper, H. and Schaffner, F, ed.), vol. 5, p. 699. Grone & Stratton, New York (1972)
  24. Lesch, R., Reutter, w., Keppler, D. and Decker, K. : Liver restitution after acute galactosamine hepatitis: Autoradiographic and biochemical studies in rats. Expl. Mol. Pathol., 12, 58-69 (1970) https://doi.org/10.1016/0014-4800(70)90075-4
  25. Wagner. H. : Antihepatotoxic flavonoids. In: Cody. V. Middleton, E. and Harhorne. J. B. (eds) : Plant flavonoids in biology and medicine: Biomedical pharmacological and structure-activity. A. R. Liss Inc. New York. p.14 (1986)
  26. Letteron, P., Labbe, G., Degott, C., Berson, A., Fromenty, B., Delaforge, M., Larrey, D. and Pessayre, D. : Mechanism for the protective effects of silyrnarin against carbon tetrachlorideinduced lipid peroxidation and hepatotoxicity in mice. Biochem. Pharmacal., 39, 2027-2034 (1990) https://doi.org/10.1016/0006-2952(90)90625-U
  27. Uliena. O, Greksak. M, Vancova. O, Zlatos. L, Galbavy. S, Bozek P, Nakano. M: Hepatoprotective effect of rooibos tea (aspalathus linearis) on $CCl_4$-induced liver damage in rats. Physiol. Res., 52, 461-466 (2003)