약학회지 (YAKHAK HOEJI)

  • 제43권6호
  • /
  • Pages.827-833
  • /
  • 1999
  • /
  • 0377-9556(pISSN)
  • /
  • 2383-9457(eISSN)
대한약학회 (The Pharmaceutical Society of Korea)
권호 표지

Biphenyl Dimethyl Dicarboxylate가 간내 Cytochrome $P_{450}$ 1A1과 2Bl 및 $CCl_4$ 유도 간독성에 미치는 영향

Effect of Biphenyl Dimethyl Dicarboxylate on Cytochrome $P_{450}$ 1A1 and 2B1 and ${CCl_4}-Induced$ Hepatotoxicity in Rat Liver

  • 김순선 (식품의약품안전청 국립독성연구소) ;
  • 오현영 (이화여자대학교 약학대학) ;
  • 김학림 (식품의약품안전청 국립독성연구소) ;
  • 양지선 (식품의약품안전청 국립독성연구소) ;
  • 김동섭 (식품의약품안전청 국립독성연구소) ;
  • 신윤용 (이화여자대학교 약학대학) ;
  • 최기환 (식품의약품안전청 국립독성연구소)
  • 발행 : 1999.12.01
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초록

In this study, we have investigated the effect of Biphenyl Dimethyl Dicarboxylate (DDB), a synthetic analogue of Schizandrin C isolated from Schizandrae Fructus on cytochrome $P_450$ lAl and 2Bl, and the protective mechanism against $CCl_4-induced$ hepatotoxicity in rat liver. After DDB was administered into male rats for different periods of time (1~7 days) and with different doses (25, 50, 100 and 200 mg/kg), mRNA levels of CYPlAl were measured by polymearse chain reaction (PCR) and assayed the activities of CYPlAl specific ethoxyresorufin-O-dealkylase (EROD) and CYP2Bl specific benzyloxyresorufin-O-dealkylase (BROD). DDB treatment resulted in increase in CYP2Bl mRNA level and BROD activity, whereas there was no change in CYPlAl mRNA level and EROD activity. This effect of DDB was time-and dose-dependent and reached maximal level by 3 day and 200 mg/kg treatment. In addition, rats were pre-treated with DDB at doses of 25, 50 or 100 mg/kg daily for 4 days, 3-hr after final treatment on the 4th day, $CCl_4$ 0.3ml/kg was intraperitonially injected into the rats to examine the effect of DDB on $CCl_4-induced$ hepatic injury. Serum levels of ALT and AST were determined and histopathological examination was done in rat liver. Furthermore, we have measured hepatic microsomal malondialdehyde(MDA) level, a parameter of lipid peroxidation. Based on serum ALT level and lipid peroxidation, pretreatment of DDB, 50 mg/kg appeared the most protective effect against $CCl_4-induced$ heapatotoxity. These results indicate that DDB stimulates CYP2Bl mRNA level and BROD activity in time and dose dependent manner and suggest that protective effect of DDB on $CCl_4-induced$ hepatotoxicity may be mediated through free radical scavenging.

키워드

참고문헌

  1. Chem. Biol. Interactions v.39 Pharmacological properties of dibenzo(a, c)cyclo-octene derivatives isolated from Fructus Schizandrae chinensis II. Induction of phenobarbital-like hepatic monooxygenases Liu, K. T.;Cresteil, T.;Columelli, S.;Lesca, P.
  2. Acta Pharm. Sinica v.14 A comparison of the protective actions of biphenyl dimethyl-dicarboxylate, transe-silbene alcoholic extracts of Fructus Schizandrae and ganoderma against experimental liver injury in mice Liu, K. T.;Wang, G. F.;Wei, H. L.;Bao, T. T.;Song, Z. Y.
  3. Chem. Biol. Interactions v.39 Pharmacological properties of dibenzo(a, c)cyclooctene derivatives isolated from Schizandrae Fructus chinensis. Interaction with rat lilver cytochrme P450 and inhibition of xenobiotic metabolism and mutagenefcity Liu, K. T.;Lesca, P.
  4. Chem. Bio. Interactions v.41 Pharmacological properties of dibenzo(a, c)cyclooctene derivatives isolated from Fructus Schizandrae chinensis III. Inhibitory effects on carbon tetrachloride-induced lipid peroxidation, metabolism and covalent binding of carbon tetrachloride to lipids Liu, K. T.;Lesca, P.
  5. Chin. Med. J. v.100 no.2 biphenyl dimethyl-dicarboxylate in Treating and Preventing Hepatitis due to Drug Poisoning Yu, H. Q.;Yang, X. Y.;Zao, S. J.
  6. 대한내과학회잡지 v.40 no.2 만성활동성 간질환 환자에서 Diphenyl Dimethyl-Dicarboxylate의 혈청 Alanine Aminotransferase치 저하효과에 관한 전향적 무자구이 선정 대조 연구 이효석;김용태;정현채;윤용범;송인성;김정룡
  7. 대한소아과 학회지 v.38 no.10 소아의 만성 간질환 환자에서 biphenyl dimethyl-dicarboxylate의 혈청 Alanine Aminotransferase치 저하효과에 관한 전향적 대조 연구 원지은;안상길;차기문;정용민;김희섭;차한;박호진
  8. Acta Pharmacologica Sinica v.13 no.6 Induction of liver microsomal cytochrome P-450 2B1 by biphenyl dimethyl-dicarboxylate in rats Yan, L.;Shanthi, R.;Jeong, P.;Yoo, S. H.;Ning, S. M.;Ma, B. L.;Lee, M. J.;Liu, G. T.;Yang, C. S.
  9. Cancer Letter v.89 Mechanistic study of the inhibiton of aflatoxin b1-induced hepatotoxity by dimethyl 4,4'-dimethoxy-5,6,5',6'-dimethylenedioxy biphenyl-2,2'-dicarboxylate Liu, T. Y.;Hwua, Y. S.;Chao, T. W.;Chi, C. W.
  10. J. Pharm. Pharmcol v.47 Enhanced effectiveness of Dimethyl-4,4'-dimethoxy 5,6,5',6'-dimethylenedioxy biphenyl-2,2'-dicarboxylate in Combinatiion with Galic Oil against Experimental Hepatic Injury in Rats and Mice Kim, S. G.;Nam, S. Y.;Jung, K. H.
  11. The Annual Report of KFDA 1 Studies on effect of natural products on hepatic metabolism(II) Choi, K. H.;Kim, S. S.;Park, Y.J.;Ahn, M. R.;Suh, S. K.;Sheen, Y. Y.;Kim, D. S.;Chang, Y. S.
  12. Biochem. Pharmacol. v.31 Studies on the in vitro interaction of mitomycin C, nitrofurantoin and paraquat with pulmonary microsomes. Stimulation of reactive oxygen dependent lipid peroxidation Trush, M. A.;Mimmaugh, E. G.;Ginburg, E.Gram, T. E.
  13. Toxicol. Lett. v.60 Effects of excitotoxins on free radical indices in mouse brain Bose, R.;Schnell, C. L.;Pinsky, C.;Zitko, V.
  14. FEBS Letters v.183 Carbon tetrachloride-inducible form of rabbit liver microsomal cytochrome P-450 Johansson, I.;Ingelman-Sunberg, M.
  15. Anal. Biochem. v.162 Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction Chomczynski, P.;Sacchi, N.
  16. Mol. Pharmacol. v.37 P450IIB gene expression in rat small intestinecloning of intestinal P450IIB1 mRNA using the polymerase chain reaction and transcriptional regulation of induction Traber, P. G.;Wang, W.;Mcdonnell, M.;Gumucio, J. J.
  17. Biochem. Pharmacol. v.34 Ethoxy-, penthoxy-, and benzyloxyphenoxazone and homologues : A series of substrates to distinggush between different induced cytochrome P-450 Burke, M. D.;Elcombe, C. R.;Halpert, J.;Thompson, S.
  18. Chem. Pharm. Bull. v.31 Kitagawa, I.;Fukuda, Y.;Yoshida, M.;Yamahura, J.;Yoshikawa, M.
  19. J. Biol. Chem. v.259 no.4 Oxygen- and Carbon-centered Free Radial Formation during Carbon Tetrachloride Metabolism McCay, P. B.;Lai, E. K.;Poyer, J. L.
  20. Bichem. Biophys. Res. Commun. v.117 Identification of dichloromethyl carbene as a metabolite of carbon tetrachloride Pohl, L.;Schulick, R.;Highet, R.;Geoge, J.
  21. FEBS Letters v.183 Carbon tetrachloride-induced lipid peroxidation dependent on ethanol-inducible form of rabbit liver microsomal cytochrome P-450 Johansson, I.;Ingelman-Sunberg, M.
  22. Mol. Pharmacol. v.25 Reductive oxygenation mechanism of metabolism of carbon tetrachloride to phosgene by cytochrome P-450 Pohl, L.;Schulick, R.;Geoge, J.
  23. Biochem. Pharm. v.39 Mechanism for the protective effects of silymarin against carbon tetrachloride-induced lipid peroxidation and hepatotoxity in mice Philippe, L.;Claude, D.;Alain, B. E.(et al.)
  24. Principles and Methods of Toxicology Hayes