$CC1_4$로 유발된 백서의 간손상에 대한 갈근의 간보호작용 연구

The Study of Protective Effect of Puerariae Radix against $CC1_4$-induced Hepatotoxicity

  • 현동환 (동국대학교 한의과대학 병리학교실) ;
  • 정선영 (동국대학교 한의과대학 병리학교실) ;
  • 정상신 (동국대학교 한의과대학 병리학교실) ;
  • 하기태 (동국대학교 한의과대학 병리학교실) ;
  • 김철호 (동국대학교 한의과대학 생화학교실) ;
  • 김동욱 (목포대학교 생물산업학부 생약자원학과) ;
  • 김준기 (동국대학교 한의과대학 병리학교실) ;
  • 최달영 (동국대학교 한의과대학 병리학교실)
  • Hyun Dong Hwan (Department of Pathology, College of Oriental Medicine, Dongguk University) ;
  • Jung Sun Yeong (Department of Pathology, College of Oriental Medicine, Dongguk University) ;
  • Jung Sang Shin (Department of Pathology, College of Oriental Medicine, Dongguk University) ;
  • Ha Ki Tae (Department of Pathology, College of Oriental Medicine, Dongguk University) ;
  • Kim Cheorl Ho (Biochemistry and Molecular Biology, College of Oriental Medicine, Dongguk University) ;
  • Kim Dong Wook (Department of Medicinal Plant Resources, Mok-po National University) ;
  • Kim June Ki (Department of Pathology, College of Oriental Medicine, Dongguk University) ;
  • Choi Dall Yeong (Department of Pathology, College of Oriental Medicine, Dongguk University)
  • 발행 : 2003.04.01

초록

In the present study, we investigated the protective effect of the Puerarie Radix water extract (PRE) against CCl₄-induced hepatotoxicity and the mechanism underlying these protective effects in the rats. The pretreatment of PRE has shown to possess a significant protective effect by lowering the serum alanine and aspartate aminoteansferase (AST and ALT) and alkaline phosphatase (ALP). This hepatoprotective action was confirmed by histological observation. In addition, the pretreatment of PRE prevented the elevation of hepatic malondialdehyde (MDA) formation and the depletion of reduced glutathione (GSH) content and catalase activity in the liver of CC1₄-injected rats. The PRE also displayed hydroxide radical scavenging activity in a dose-dependent manner (IC50 = 83.6 μg/ml), as assayed by electron spin resonance (ESR) spin-trapping technique. Moreover, the expression of cytochrome P450 2E1 (CYP2E1) mRNA, as measured by reverse transcriptase-polymerase chain reaction (RT-PCR), was significantly decreased in the liver of PRE-pretreated rats when compared with that in the liver of control group. Based on these results, it was suggested that the hepatoprotective effects of the PRE may be related to antioxidant effects and regulation of CYP2E1 gene expression.

키워드

참고문헌

  1. 木草綱目 v.18 李時珍
  2. 圖說漢方醫藥大辭典 v.1 陳在仁
  3. 조선대학교 대학원 석사학위논문 갈근 Ethanol 엑기스의 실헙적 위궤양에 미치는 영향 엄기진
  4. Zhonghua Yi Xue Za Zhi v.5 Studies on flavones of Radix puerariae. Fang CC>;Lin M.;Sun CM.;Liu HM.;Lang HY.
  5. Chin. Med. J. (Engl). v.98 no.11 Pharmacologic studies on radix puerariae: effect of puerarin on regional myocardial blood flow and cardiac hemodynamics in dogs with acute myocardial ischemia. Fan LL;O'Keefe DO;Powell WW Jr.
  6. 덕성여자대학교 대학원 석사학위논문 한국산 야생 식물이 당뇨 유발 흰쥐의 혈당 수준에 미치는 영향 : 간글, 산수유, 오미자, 용규 및 치자를 중심으로 조재선
  7. 조선대학교 대학원 석사학위논문 葛根抽出物이 Alloxan으로 誘發된 家兎의 高血糖에 미치는 영향 홍자형
  8. 경성대학교 대학원 석사학위논문 갈근의 항산화성분 및 구조-활성 상관관계 박창훈
  9. 동아대학교 대학원 석사학위논문 갈근 추출물이 에탄올을 투여한 흰쥐의지질과산화에 미치는 영향 김은실
  10. Yakugaku Zasshi. v.113 no.12 A simultaneous determination of daidzin and puerarin and determination of daidzein in Oriental pharmaceutical decoctions containing puerariae radix by ion-pair high-performance liquid chromatography. Yasuda T;Momma N;Ohsawa K.
  11. CIin. Exp. Res. v.17 no.6 Biochemical studies of a new class of alcohol dehydrogenase inhibitors from Radix puerariae. Alcohol. Keung WM. https://doi.org/10.1111/j.1530-0277.1993.tb05238.x
  12. Planta Med. v.64 no.5 Preventive effects of saponins from the Pueraria lobata root on in vitro immunological liver injury of rat primary hepatocyte cultures. Arao T;Udayama M;Kinjo J;Nohara T. https://doi.org/10.1055/s-2006-957471
  13. Life Sci. v.67 no.24 Comparison between chinese medical herb Pueraria lobata crude extract and its main isoflavone puerarin antioxidant properties and effects on rat liver CYP-catalysed drug metabolism. Guerra MC;Speroni E;Broccoli M;Cangini M;Pasini P;Minghett A;Crespi-PereIlino N;Mirasoli M;CanteIIi-Forti G;Paolini M. https://doi.org/10.1016/S0024-3205(00)00885-7
  14. 경북대학교 대학원 박사학위논문 사염화탄소 투여로 인한 血淸病 各種酵素의 活性變動에 關하여 조병권
  15. 영남대학교 대학원 석사학위논문 사염화탄소의 반복투여가 백서 간장에 미치는 병리조직화적 연구 서혜진
  16. Res. Commun. Chern. Pathol. Pharmacol. v.35 no.2 Covalent binding of carbon tetrachloride metabolites to the heme moiety of cytochrome P-450 and its degradation products Fernandez G;Villarruel MC;de Toranzo EG;Castro JA.
  17. Biochem. J. v.246 no.2 Free-radical metabolism of carbon tetrachloride in rat liver mitochondria. A study of the mechanism of activation. Tomasi A;Albano E;Banni S;Botti B;Corongiu F;Dessi MA;Iannone A;Vannini V;Dianzani MU. https://doi.org/10.1042/bj2460313
  18. Cell. Biochem. Funct. v.6 no.2 Lipid peroxidation in purified plasma membrane fractions of rat liver in relation to the hepatoxicity of carbon tetrachloride. Le Page RN;Cheeseman KH;Osman N;Slater TF. https://doi.org/10.1002/cbf.290060203
  19. J. Biol Chem. v.265 no.15 The in vitro NADPH-dependent inhibition by $CCl_4$ of the ATP-dependent calcium uptake of hepatic microsomes from male rats. Studies on the mechanism of the inactivation of the hepatic microsomal calcium pump by the $CCl_3$.radical. Srivastava SP;Chen NQ;Holtzman JL.
  20. Am. J. Clin. Pathol. v.28 A colorimetric method for determination of serum glutamic oxaloacetic and glutamic pyruvic transaminases Reitman, S.;Frankel, S.
  21. Agressologie. v.14 no.5 Changes of enzyme activity in some organs following thymectomy. Petkova J;Popova N;Kemileva Z.
  22. Anal. Biochem. v.95 no.2 Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Ohkawa H;Ohishi N;Yagi K. https://doi.org/10.1016/0003-2697(79)90738-3
  23. Arch. Biochem. Biophys. v.82 Tissue sulfhydryl groups. Ellman, G. L. https://doi.org/10.1016/0003-9861(59)90090-6
  24. Methods Enzymol. v.105 Catalase in vitro. Aebi H. https://doi.org/10.1016/S0076-6879(84)05016-3
  25. YAKUGAKU ZASSHI. v.106 no.8 Experimental Production of Various Types of Cholestasis and the Effects of Cystemine. Kamokawa, A.;Ohta, S.;Tatsugi, A.;Kumasaka, M.;Shinoda, M. https://doi.org/10.1248/yakushi1947.106.8_709
  26. Biochem. Pharmacol. v.31 no.5 Selective early loss of polypeptides in liver micro somes of $CCl_4$-treated rats. Relationship to cytochrome P-450 content. Noguchi, T.;Fong, K. L.;Lai, E. K.;Olson, L.;McCay, P. B. https://doi.org/10.1016/0006-2952(82)90439-7
  27. J. BioI. Chem. v.251 no.16 Lipid peroxidation and alteration of membrane lipids in isolated hepatocytes exposed to carbon tetrachloride. Weddle, C. C.;Hornbrook, K. R.; McCay, P. B.
  28. Hepatology v.11 no.3 The hepatocyte protein synthesis defect induced by galactosamine involves hypomethylation of ribosomal RNA. Clawson GA;Sesno J;Milam K;Wang YF;Gabriel C. https://doi.org/10.1002/hep.1840110314
  29. Enzyme. v.23 no.5 Dysregulation of protein synthesis in injured liver. A comparative study on microsomal and cytosole enzyme activities, microsomal lipoperoxidation and polysomal patten in D-galactosamine and carbon tetrachloride-injured livers. Watanabe A;Akamatsu K;Takesue A;Taketa K. https://doi.org/10.1159/000458596
  30. Proc. Natl. Acad. Sci. USA. v.90 no.21 Daidzin and daidzein suppress free-choice ethanol intake by Syrian golden hamsters. Keung WM;Vallee BL. https://doi.org/10.1073/pnas.90.21.10008
  31. Life Sci. v.36 no.6 Carbon tetrachloride-induced inhibition of hepatocyte lipoprotein secretion: functional impairment of Golgi apparatus in the early phases of such injury. Poli G;Chiarpotto E;Albano E;Cottalasso D;Nanni G;Marinari UM;Bassi AM;Dianzani MU. https://doi.org/10.1016/0024-3205(85)90634-4
  32. Cell Biochem Funct. v.9 no.2 In VIVO and in vitro evidence concerning the role of lipid peroxidation in the mechanism of hepatocyte death due to carbon tetrachloride. Biasi F;Albano E;Chiarpotto E;Corongiu FP;Pronzato MA;Marinari UM;Parola M;Dianzani MU;Poli G. https://doi.org/10.1002/cbf.290090208
  33. 개정증보판 본초학 이상인
  34. 신편중약대사전
  35. Am. J. Clin. Pathol. v.28 A colorimetric method for the determination of serum glutamic oxaloacetic and glutamic pyruvate transaminases Retman, S.;Frankel, S.
  36. Sulfur Amino Acids, : Biochemical and Clinical Aspects Liver glutatione as a reservior of L-cystine. Higashi, T.;Tateishi, N.;sakamoto, Y.
  37. Res Commun Chem Pathol Pharmacol. v.19 no.2 Carbon tetrachloride activation, lipid peroxidation and liver necrosis in different strains of mice. de Toranzo EG;Gomez MI;Castro JA.
  38. Food Chem Toxicol v.37 no.9-10 Intracellular antioxidants: from chemical to biochemical mechanisms. Chaudiere J,;Ferrari-Iliou R. https://doi.org/10.1016/S0278-6915(99)00090-3
  39. Free Radical Biology & Medicine v.11 Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. ESTERBAUER H.;SCHAUR RJ.;ZOLLNER H. https://doi.org/10.1016/0891-5849(91)90192-6
  40. Glutathione: Chemical Biochemical and Medical Aspects DOLPHIN D.;POULSON R.;AVRAMOVIC O.(Eds.)
  41. Glutathione: chemical, biochemical and medical aspects Enzymatic and chemical methods for the determination of glutathione. ANDERSON M.E.; DOLPHIN D.;POULSON R;AVRAMOVIC O.(Eds.)
  42. Physiol. Rev. v.50 Catalase: Physicial and Chemical Properties, Mechanism of Catalysis, and Physiological Role Deisseroth, A.; Dounce, AL. https://doi.org/10.1152/physrev.1970.50.3.319
  43. Prog. Biophys. Mol. BioI. v.72 Understanding the Structure and Function of Catalases: Clues from Molecular Evolution and In Vitro Mutagenesis Zamocky, M.;Koller, F. https://doi.org/10.1016/S0079-6107(98)00058-3
  44. Methods Enzymol. v.233 In vivo detection of radical adducts by electron spin resonance. Mason RP;Knecht KT. https://doi.org/10.1016/S0076-6879(94)33013-1
  45. J Ethnopharmacol. v.60 no.1 Evaluation of the hepatoprotective and antioxidant activity of Boehmeria nivea var. nivea and B. nivea var. tenacissima. Lin CC;Yen MH;Lo TS;Lin JM. https://doi.org/10.1016/S0378-8741(97)00122-0
  46. Methods Enzymol. v.105 Spin trapping of superoxide and hydroxyl radicals. Rosen GM;Rauckman EJ. https://doi.org/10.1016/S0076-6879(84)05026-6
  47. Free Radic BioI Med. v.32 no.5 Metal-independent production of hydroxyl radicals by halogenated quinones and hydrogen peroxide: an ESR spin trapping study. Zhu BZ;Zhao HT;Kalyanaraman B;Frei B. https://doi.org/10.1016/S0891-5849(01)00824-3
  48. Res. Common. Chem. Pathol. Pharmacol. v.28 Vitamin E and inhibition of platelet lipoxygenase. Gwebu, E. T.;Ttewyn, R. W.;Cornwell, D. G;Panganamala, R. V.
  49. Res. Common. Chem. Pathol. Pharmacol. v.28 Vitamin E and inhibition of platelet Iipoxygenase. Gwebu, E. T.;Ttewyn, R. W.;Cornwell, D. G.;Panganamala, R. V.
  50. Toxicol Appl Pharmacol. v.153 no.1 Resistance to carbon tetrachloride-induced hepatotoxicity in mice which lack CYP2E1 expression. Wong FW;Chan WY;Lee SS. https://doi.org/10.1006/taap.1998.8547