Effect of Green Tea Catechin on Acute Hepatotoxicity in Rats

랫트의 간 손상에 대한 녹차카테킨의 보호 및 치료효과

  • 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)
  • 육동연 (충북대학교 약학대학 생물건강산업개발연구센터) ;
  • 이미애 (청주대학교 사회과학대학) ;
  • 윤여표 (충북대학교 약학대학 생물건강산업개발연구센터)
  • Published : 2004.09.01

Abstract

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.

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.

Keywords

References

  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)