Study on the Protective Effect of Corni Fructus against Free Radical Mediated Liver Damage

산수유의 유리자유기에 의한 간손상 보호효과

  • Ha, Ki-Tae (Department of Pathology, College of Oriental Medicine, Dongguk University) ;
  • Kim, Young-Mi (Department of Pathology, College of Oriental Medicine, Dongguk University) ;
  • Kim, Cheorl-Ho (Molecular and Cellular Glycobiology Unit, Department of Biological Sciences, SungKyunKwan University) ;
  • Kim, Dong-Wook (Department of Pharmacognostic Resources, College of Natural Science, Mokpo National University) ;
  • Choi, Dall-Yeong (Department of Pathology, College of Oriental Medicine, Dongguk University) ;
  • Kim, June-Ki (Department of Pathology, College of Oriental Medicine, Dongguk University)
  • 하기태 (동국대학교 한의과대학 병리학교실) ;
  • 김영미 (동국대학교 한의과대학 병리학교실) ;
  • 김철호 (성균관대학교 자연과학부 생명과학과) ;
  • 김동욱 (목포대학교 생명공학부 생약자원전공) ;
  • 최달영 (동국대학교 한의과대학 병리학교실) ;
  • 김준기 (동국대학교 한의과대학 병리학교실)
  • Published : 2007.12.25

Abstract

Carbon tetrachloride ($CCl_4$)-induced liver injury depends on a toxic agent that has to be metabolized by the liver NAPDH-cytochrome P450 enzyme system to a highly reactive intermediate. Alternations in the activity of cytochrome P450 enzymes affect the susceptibility to hepatic injury from $CCl_4$. In this study, we evaluated the potential protective activity of the traditional Korean medicinal herb, Corni fructus (CF), against an experimental model of hepatotoxicity induced by $CCl_4$. The CF exhibited a hepatoprotective activity against $CCl_4-induced$ liver damage in Sprague-Dawley (SD) rats, as measured by GOT, GPT, ALP and histological observation. The CF also showed significant decrease of malodialdehyde (MDA) and increase of glutathion (GSH), catalase activity in rat liver homogenate. In addition, the expression of CYP2E1, as measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis, was significantly decreased in the liver of CF treated SD rats. But $CCl_4$ and CF has no significant effect on 1A1 and 3A1 isoform of cytochrome P450. Based on these findings, it is suggested that hepatoprotective effects of CF possibly related to antioxidative effects and regulation of CYP2E1 expression.

Keywords

References

  1. 조병권. 사염화탄소 투여로 인한 血淸內 各種酵素의 活性變動에 關하여, 경북대학교 대학원 박사학위논문, 1984
  2. 서혜진. 사염화탄소의 반복투여가 백서 간장에 미치는 병리조직학적 연구, 영남대학교 대학원 석사학위논문, 1987
  3. Fernandez, G., Villarruel, M.C., de Toranzo, E.G., Castro, J.A. Covalent binding of carbon tetrachloride metabolites to the heme moiety of cytochrome P-450 and its degradation products. Res. Commun. Chem. Pathol. Pharmacol. 35(2):283-290, 1982
  4. Tomasi, A., Albano, E., Banni, S., Botti, B., Corongiu, F., Dessi, M.A., Iannone, A., Vannini, V., Dianzani, M.U. Free-radical metabolism of carbon tetrachloride in rat liver mitochondria. A study of the mechanism of activation. Biochem. J. 246(2):313-317, 1987 https://doi.org/10.1042/bj2460313
  5. Le Page, R.N., Cheeseman, K.H., Osman, N., Slater, T.F. Lipid peroxidation in purified plasma membrane fractions of rat liver in relation to the hepatoxicity of carbon tetrachloride. Cell. Biochem. Funct. 6(2):87-99, 1988 https://doi.org/10.1002/cbf.290060203
  6. 陳存仁. 圖說漢方醫藥大辭典(III). 東京, 講談社, p 208, 1982
  7. 전국한의과대학 본초학교수 공편. 본초학. 서울, 영림사, pp 626-627, 1991
  8. 王旭高. 西溪書屋夜話錄. 王旭高醫書六種. 北京, 學苑出版社, p 110, 1996
  9. 朴瑛卿. 山茱萸 種子의 抗糖尿 效果-Streptozotocin 유발 고혈당 흰쥐에 미치는 영향. 中央大 大學院, 석사학위논문, 1991
  10. 朴炫宣. 산수유 약침의 항산화 작용에 관한 실험적 연구. 大田大 大學院, 석사학위논문, 1998
  11. Mau, J., Chen, C., Hsieh, P. Antimicrobial effect of extracts from Chinese chive, cinnamon, and corni fructus. J Agric Food Chem. 49(1):183-188, 2001 https://doi.org/10.1021/jf000263c
  12. Jeng, H., Wu, C.M., Su, S.J., Chang, W.C. A substance isolated from Cornus officinalis enhances the motility of human sperm. Am J Chin Med. 25(3-4):301-306, 1997 https://doi.org/10.1142/S0192415X97000330
  13. Reitman, S. and Frankel, S. A colorimetric method for determination of serum glutamic oxaloacetic and glutamic pyruvic transaminases, Am. J. Clin. Pathol. 28: 58-63, 1957
  14. Petkova, J., Popova, N., Kemileva, Z. Changes of enzyme activity in some organs following thymectomy. Agressologie. 14(5):323-326, 1973
  15. Ohkawa, H., Ohishi, N., Yagi, K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem. 95(2):351-358, 1979 https://doi.org/10.1016/0003-2697(79)90738-3
  16. Ellman, G.L. Tissue sulfhydryl groups. Arch. Biochem. Biophys. 82: 70-77, 1959 https://doi.org/10.1016/0003-9861(59)90090-6
  17. Aebi, H. Catalase in vitro. Methods Enzymol. 105: 121-126, 1984 https://doi.org/10.1016/S0076-6879(84)05016-3
  18. Poli, G. Liver damage due to free radicals. Br Med Bull. 49(3):604-620, 1993 https://doi.org/10.1093/oxfordjournals.bmb.a072634
  19. Kamokawa, A., Ohta, S., Tatsugi, A., Kumasaka, M. and Shinoda, M. Experimental Production of Various Types of Cholestasis and the Effects of Cystemine. YAKUGAKU ZASSHI. 106(8):709, 1986 https://doi.org/10.1248/yakushi1947.106.8_709
  20. Noguchi, T., Fong, K.L., Lai, E.K., Olson, L., and McCay, P.B. Selective early loss of polypeptides in liver microsomes of CCl4-treated rats. Relationship to cytochrome P-450 content. Biochem. Pharmacol. 31(5):609-614, 1982 https://doi.org/10.1016/0006-2952(82)90439-7
  21. Weddle, C.C., Hornbrook, K.R. and McCay, P.B. Lipid peroxidation and alteration of membrane lipids in isolated hepatocytes exposed to carbon tetrachloride. J. Biol. Chem. 251(16):4973-4978, 1976
  22. Clawson, G.A., Sesno, J., Milam, K., Wang, Y.F., Gabriel, C. The hepatocyte protein synthesis defect induced by galactosamine involves hypomethylation of ribosomal RNA. Hepatology 11(3):428-434, 1990 https://doi.org/10.1002/hep.1840110314
  23. Watanabe, A., Akamatsu, K., Takesue, A., Taketa, K. Dysregulation of protein synthesis in injured liver. A comparative study on microsomal and cytosole enzyme activities, microsomal lipoperoxidation and polysomal pattern in D-galactosamine and carbon tetrachloride- injured livers. Enzyme. 23(5):320-327, 1978 https://doi.org/10.1159/000458596
  24. Poli, G., Chiarpotto, E., Albano, E., Cottalasso, D., Nanni, G., Marinari, U.M., Bassi, A.M., Dianzani, M.U. Carbon tetrachloride-induced inhibition of hepatocyte lipoprotein secretion: functional impairment of Golgi apparatus in the early phases of such injury. Life Sci. 36(6):533-539, 1985 https://doi.org/10.1016/0024-3205(85)90634-4
  25. Biasi, F., Albano, E., Chiarpotto, E., Corongiu, F.P., Pronzato, M.A., Marinari, U.M., Parola, M., Dianzani, M.U., Poli, G. In vivo and in vitro evidence concerning the role of lipid peroxidation in the mechanism of hepatocyte death due to carbon tetrachloride. Cell Biochem Funct. 9(2):111-118, 1991 https://doi.org/10.1002/cbf.290090208
  26. 黃度淵. 方藥合編. 서울, 南山堂, p 121, 166, 1996
  27. 張介賓. 景岳全書. 北京, 人民衛生出版社, p 1650, 1992
  28. 許浚. 東醫寶鑑. 서울, 南山堂, p 971, 1992
  29. 王旭高. 西溪書屋夜話錄. 王旭高醫書六種. 北京, 學苑出版社, p 110, 1996
  30. Chenoweth, M.B. and Hake, C.L. The smaller halogenated aliphatic hydrocarbons. Ann. Rev. Pharmac. 2: 363-398, 1962 https://doi.org/10.1146/annurev.pa.02.040162.002051
  31. 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. 33(2):84-88, 1985 https://doi.org/10.1159/000469411
  32. Esterbauer, H., Schaur, R.J., Zollner, H. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radical Biology & Medicine. 11: 81-128, 1991 https://doi.org/10.1016/0891-5849(91)90192-6
  33. Dolphin, D., Poulson, R. and Avramovic, O., Eds. Glutathione: Chemical, Biochemical and Medical Aspects, Vols A & B, J. WILEY and Sons, 1989
  34. Anderson, M.E. Enzymatic and chemical methods for the determination of glutathione; In: Glutathione: chemical, biochemical and medical aspects, Vol.A, Dolphin D., Poulson R. and Avramovic O. Eds., John WILEY and Sons, pp 339-365, 1989
  35. Chaudiere, J., Ferrari-Iliou, R. Intracellular antioxidants: from chemical to biochemical mechanisms. Food Chem Toxicol 37(9-10):949-962, 1999 https://doi.org/10.1016/S0278-6915(99)00090-3
  36. Deisseroth, A. & Dounce, A.L. Catalase: Physicial and Chemical Properties, Mechanism of Catalysis, and Physiological Role, Physiol. Rev. 50: 319-375, 1970 https://doi.org/10.1152/physrev.1970.50.3.319
  37. Biasi, F., Albano, E., Chiarpotto, E., Corongiu, F.P., Pronzato, M.A., Marinari, U.M., Parola, M., Dianzani, M.U., Poli, G. In vivo and in vitro evidence concerning the role of lipid peroxidation in the mechanism of hepatocyte death due to carbon tetrachloride. Cell Biochem Funct. 9(2):111-118, 1991 https://doi.org/10.1002/cbf.290090208
  38. Gwebu, E.T., Ttewyn, R.W., Cornwell, D.G. and Panganamala, R.V. Vitamin E and inhibition of platelet lipoxygenase. Res. Common. Chem. Pathol. Pharmacol. 28: 361-369, 1980
  39. Rogers, J.F., Nafziger, A.N., Bertino, J.S. Jr. Pharmacogenetics affects dosing, efficacy, and toxicity of cytochrome P450-metabolized drugs. Am J Med. 113(9):746-750, 2002 https://doi.org/10.1016/S0002-9343(02)01363-3
  40. Koop, D.R. Oxidative and reductive metabolism by cytochrome P450 2E1. FASEB J. 6(2):724-730, 1992 https://doi.org/10.1096/fasebj.6.2.1537462
  41. Degawa, M., Mikami, K., Namiki, M., Hashimoto, Y. Inhibition of the induction and activity of hepatic P450IA isozymes by in vivo administration of carbon tetrachloride to rats. Biol Pharm Bull. 16(12):1248-1250, 1993 https://doi.org/10.1248/bpb.16.1248
  42. Ronis, M.J., Ingelman-Sundberg, M., Badger, T.M. Induction, suppression and inhibition of multiple hepatic cytochrome P450 isozymes in the male rat and bobwhite quail (Colinus virginianus) by ergosterol biosynthesis inhibiting fungicides (EBIFs). Biochem Pharmacol. 48(10): 1953-1965, 1994 https://doi.org/10.1016/0006-2952(94)90594-0
  43. Wong, F.W., Chan, W.Y., Lee, S.S. Resistance to carbon tetrachloride- induced hepatotoxicity in mice which lack CYP2E1 expression. Toxicol Appl Pharmacol. 153(1):109-118, 1998 https://doi.org/10.1006/taap.1998.8547