Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지

Therapeutic Effect of the GODEX on the Liver Chirrosis Induced by CCl4 and Ethanol in the Rat

사염화탄소와 에탄올에 의해 유발된 랫드의 간경변에서 GODEX (Hepadif-S capsule)의 치료 효과

  • 신지순 (충북대학교 수의과대학 실험동물의학교실) ;
  • 정은용 (충북대학교 수의과대학 실험동물의학교실) ;
  • 이민호 (한양대학교 서울병원 소화기내과) ;
  • 강종구 (충북대학교 수의과대학 실험동물의학교실)
  • Published : 2002.09.01
Download PDF
⟨ Previous Next ⟩

Abstract

The hepato-protective activity of the GODEX (Hepadif-s capsule) has been studied in the rats against $CCl_4$-ethanol induced liver toxicity. The rats were oral1y treated with $CCl_4$ (corn oil/ $CCl_4$ 1:1, 1 mg/kg). And one week passes, $CCl_4$(0.4 mg/kg) administered two times a week for 7 weeks. The drugs have been administered every two days for 4 weeks after $CCl_4$ injection. The experimental groups have consisted of the GODEX (250 mg/kg), Hepadif (200 mg/kg), DDB complex (DDB 50 mg/kg and garlic oil powder 50 mg/kg), DDB (50 mg/kg), and vehicle control respectively. There was a significant decrement on the serum level of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin in all treated groups. Specially, ALT level of GODEX and Hepadif only treated groups was decreased c1early. Also, serum albumin level was significantly enhanced in GODEX treated group compared with control and DDB treated groups. In histological results, hepatocellular vacuolar degeneration, lobular restructure and necrosis of bile duct were severely showed in control. But other treated groups showed centerilobular degeneration and mild hyper-plasia. Hepadif or DDB has a effects of the recovery on serum parameters and structure ill liver injury. When it was compared GODEX to Hepadif alone or DDB complex or DDB, it suggested to have the best activity of the liver recovery.

Keywords

References

  1. Anthony, P. P., Ishak, K. G. and Nayak, N. C. (1977). The morphology of cirrhosis: definition, nomenclature and classification. Bull WHO., 55, 521
  2. Anthony, P. P. Ishak, K. G. and Nayak, N. C. (1987). The morphology of cirrhosis. J. Clin. Pathol., 31, 395 https://doi.org/10.1136/jcp.31.5.395
  3. Bosma, A., Brouwer, A., Seifert, W. F. and Knook, D. L. (1988). Synergism between ethanol and carbon tetrachlo- ride in the generation of liver fibrosis. J. Pathol, 156, 15- 21 https://doi.org/10.1002/path.1711560106
  4. Gomez, M. I. and Castro, J. A. (1980). Covalent binding of carbon tetrachloride mctabolite to liver nuclear DNA, proteins and lipids. Toxicol. AppI. Pharmacol., 56, 199-206 https://doi.org/10.1016/0041-008X(80)90290-2
  5. Hall, P. M., Plummer, J. L., Ilsley, A. H., Ahern, M. J., Cmielewski, P. L. and Williams, R. A. (1994). The patho- logy of liver injury induced by the chronic administration of alcohol and 'low-dose' carbon tetrachloride in Porton rats. J. Gastroenterol. Hepatol., 9, 250-256 https://doi.org/10.1111/j.1440-1746.1994.tb01719.x
  6. Hruszkcwyez, A. M., Glende, E. A. and Recknagel, R. 0. (1987). Destruction of microsomal cytochrome P-450 and glucose-6-phosphate by lipids extracted from peroxidized microsomes. Toxicol. Appl. Pharmacol., 46, 695-702 https://doi.org/10.1016/0041-008X(78)90314-9
  7. Ikatsu, H. and Nakajima, T. (1992). Hepatotoxic interaction between carbon tetrachloride and chloroform in ethanol treated rats. Arch Toxicol., 66, 580-586 https://doi.org/10.1007/BF01973389
  8. Jamall, I. S., Inelli, V. N. and Que-Hee, S. S. (1981). A simple method to determine nanogram levels of 4-hydroxyproline in biological tissues. Analytical biochemistry, 112, 70-75 https://doi.org/10.1016/0003-2697(81)90261-X
  9. Kim S. H., Bae, Y. J., Lec, K. H. and Lee, S. B. (1995). Effect of Biphenyl Dimetyl Dicarboxylate on Chemical-Induced Hepatotoxicity. Korean J. Toxicol, 11, 181-185
  10. Kim, S. S., Oh, H. Y., Kim, H. R., Yang, J. S., Kim, D. S., Sheen, Y. Y., and Choi, K. H. (1999). Effect of bipheyl dimethyl dicarboxylate on cytochrome P450 1A1 and 2B1 and $CCl_4$-induced bepato toxicity in rat liver. Yakhak Hoeji., 43, 827-833
  11. Long, R. M. and Moorc, L. (1986). Elevated cytosolic calcium in rat hepatocytes exposed to carbon tetrachloride. J. Pharmacol. and Exp. Ther., 238, 186-191
  12. Long, R. M. and Moore, L. (1986). Inhibition of liver endo- plasmic reticulum pump by carbon tetrachloride and releases of a sequestered calcium pool. Biochem. Pharma- col., 35, 4130-4137
  13. Miyazawa, S., Furuta, S. and Hashimoto, T. (1992) Reduction of $\beta$-oxidation capacity of rat liver mitochondria by feeding orotic acid. Biochim. Biophys. Acta., 711, 494-502
  14. Pauline, De-la M., Hall, J. L., Plummer, A. H., Ilsley, M. and Cousins, J. (1991). Hepatic fibrosis and cirrhosis after Chronic administration of Alcohol and 'Low-dose' carbon tetrachloride vapor in the rat. Hepatology., 13, 815-819 https://doi.org/10.1002/hep.1840130502
  15. Plaa, G. L. (1991). Toxic responses of the liver in Casarett and Doull's Toxicology (Amdur, M. 0, Doull, J. and Klassen, C.D. Eds.). pp 334-353. Pergamin Press., New York
  16. Plummer, J. L., Hall, P. D., Cmielewski, P. L., Lisley, A.H. and Ahem, M. J. (1994). Alcohol and 'low- dose' carbon tetra-chloride-induced cirrhosis in rats using different methods of alcohol feeding, Alcohol Clinical Exp Res., 18, 1502-1505 https://doi.org/10.1111/j.1530-0277.1994.tb01457.x
  17. Ryoo, J. W. and Buschmann, R. J. (1983). A morphometric analysis of the hypertrophy of the expermental liver cirrhosis. Virchows Arch'Patholol. Ana'., 400, 173-186 https://doi.org/10.1007/BF00585499
  18. Sherlock, S. and Dooley, J. (1997). Diseases of the liver and biliary system., lOth ed. pp. 303-384 Blackwell Science Press
  19. Thomas, B. D. and Mariani, M. E. (1989). Comparison of metabolic effects of carbon tetrachloride and 1,2- dichrooethane added in vitro to sliced of rat liver. Toxico. in vitro., 3, 159-168 https://doi.org/10.1016/0887-2333(89)90060-X
  20. Tokmakjian, S. D. and Haines, D. S. (1985). Early effects of dietary orotic acid upon liver lioid synthesis and bile cholesterol secretion in rats. J. Lipid Res., 26, 478-486