Taraxacum Mongolicum H. Suppress Hepatoprotective Activity by Increasing Liver Antioxidant Enzyme in Carbon Tetrachloride($CCl_4$)-induced Hepatotoxicity in Rats

흰쥐에서 민들레 추출물이 사염화탄소에 의한 산화적 스트레스의 경감기전

  • Received : 2010.04.05
  • Accepted : 2010.06.08
  • Published : 2010.06.25

Abstract

Pretreatment with Taraxacum Mongolicum H(TMH) prior to the administration of on $CCl_4$ significantly prevented the increased serum enzymatic activity of aminotransferase(ALT, AST), gamma-glutamyl transpeptidase(GGT) and bilirubin concentration in dose-dependent manner. In addition, pretreatment with TMH also significantly restored the elevation of hepatic malondialdehyde formation and the depletion of reduced glutathione content in the liver $CCl_4$-intoxicated rats. The restoration of microsomal aniline hydroxylase and aminopyrine N-demethylase activities indicated the improvement in functional status of endoplasmic reticulum. $CCl_4$-induced hepatotoxicity was also essentially prevented, as indicated by a liver histopathologic study. TMH showed antioxidant effects in $FeCl_2$-ascorbate-induced lipid peroxidation in rat liver homogenate and in superoxide radical scavenging activity. Our results suggest that the protective effect of TMH against $CCl_4$-induced hepatotoxicity possibly involve mechanisms related to its ability to block p450-mediated $CCl_4$ bioactivation and free radical scavenging effects.

Keywords

References

  1. Valko, M., Leibfritz, D., Cronin, M.T.D., Mazur, M., Telser, J. Free radicals and antioxidant in normal physiological functions and human disease. Intern. J. Cell Biol. 39: 44-84, 2007. https://doi.org/10.1016/j.biocel.2006.07.001
  2. Fridorich, I. Biological effects of the superoxide radical. Arch. Biophys. 247: 1-11, 1986. https://doi.org/10.1016/0003-9861(86)90526-6
  3. Nirmal, C.K., Carl, M.P. Catalase, superoxide dismutase, glutathione reductase and thiobarbituric acid-reactive products in normal and dystrophic human muscle. Clin. Chim. Acta. 94: 277-280, 1979. https://doi.org/10.1016/0009-8981(79)90076-7
  4. Vitaly, A.R., Hartmut, B.S. Ascorbyl radical as natural indicator of oxidative stress: quantitative regularities. Free Radical Biol. Med. 17(2):93-103, 1994. https://doi.org/10.1016/0891-5849(94)90107-4
  5. Mun, K.S. Asteraceta(Compositae). In: Components and uses of medical plants. Ilweolseogak. Seoul, Korea. pp 750-751, 1999.
  6. 한국식품공업협회. 식품공전. 문영사, 서울, pp 25-34, 2001.
  7. Namba, T. The encyclopedia of Waken-Yaku with color pictures. Hoikusha, Osaka, Japan. 1: 68-71, 1993.
  8. Chen, Z. Clinical study of 96 cases with chronic hepatitis B treated with jiedu yanggan gao by double-blind method. Zhong Xi Yi Jie He Za Zhi. 2: 71-74, 1990.
  9. Zheng, M. Experimental study of 472 herbs with antiviral action against the herpes simplex virus. Zhong Xi Yi Jie He Za Zhi. 1: 39-41, 1990.
  10. Liu, X.R., Han, W.Q., Sun, D.R. Treatment of intestinal metaplasia and atypical hyperplasia by gastric mucosa with xiao wei yan powder Zhongguo. Zhong Xi Yi Jie He Za Zhi. 10: 602-603, 1992.
  11. Martin, M.I., Gonzalez, J., Munoz, J.M., Alonso, L., Esteller, A., Fermoso, J. Changes in hepatic and serum $\gamma$-glutamyltransferase activities following chronic ethanol intake in rats. Drug Alcohol Dependence, 21(1):19-23, 1988. https://doi.org/10.1016/0376-8716(88)90005-1
  12. Ohkawa, H., Ohishi, N. and Yaki, K. Assay for lipid peroxide in animal tissues by thiobarbituric acid reaction. Anal. Biochem. 95: 351-358, 1979. https://doi.org/10.1016/0003-2697(79)90738-3
  13. Saville, A. Scheme for the colorimetric determination of microgram amounts of thiols, Analyst, 83: 670-672, 1958. https://doi.org/10.1039/an9588300670
  14. Nash, T. The colorimetric estimation of formaldehyde by means of the hentisch reaction. J. Biol. Chem. 55: 412-416, 1953.
  15. Bidlack, W.R., Lowry, G.L. Multiple drug metabolism: p-Nitroanisole reversal of acetone enhanced aniline hydroxylation. Biochem. Pharmacol. 31: 311-317, 1982. https://doi.org/10.1016/0006-2952(82)90176-9
  16. Habig, W.H., Pabist, M.J., Jakoby, W.B. Glutathione S-transferase: The first enzymatic step in mercapturic acid formation. J. Biol. Chem. 249: 7130-1739, 1974.
  17. Lowry, O.H., Rodebrough, N.J., Farr, A.L., Randall, R.J. Protein measurement with the folin phenol reagent. J. Biol. Chem. 193: 265-275, 1951.
  18. Shull, S., Heintz, N.H., Periasamy, M., Manohar, M., Janssen, Y.M., Marsh, J.P., Mossman, B.T. Differential regulation of antioxidant enzymes in response to oxidants. J. Biol. Chem. 266(36):24398-24403, 1991.
  19. Iizawa, O., Kato, T., Tagami, H., Akamatsu, H., Niwa, Y. Long-term follow-up study of changes in lipid peroxide levels and the activity of superoxide dismutase, catalase and glutathione peroxidase in mouse skin after acute and chronic UV irradiation. Arch. Dermatol. Res. 286(1):47-52, 1994. https://doi.org/10.1007/BF00375843
  20. Halliwell, B., Gutteridge, J.M.C. Role of free radicals and catalytic metalytic ions in human disease: an overview. Methods in Enzymology. 186: 1-85, 1990. https://doi.org/10.1016/0076-6879(90)86093-B
  21. Freman, B.A., Crapo, J.D. Biology of disease : Free radicals and tissue injury. Lab. Invest. 47: 412-426, 1982.
  22. Bauer, J.D. Clinical laboratory methods. St. Louis: C.V. Mosby Co. pp 578-579, 700-703, 1995.
  23. Sarkar, N.K. Alanine and aspartate aminotransferase activities in serum and various subcellular fractions from the livers of different species. Inter. J. Biochem. 5(4):375-381, 1974. https://doi.org/10.1016/0020-711X(74)90133-5
  24. Mitchell, J.S., Daniel, S.M., Marshall, M.K. $\gamma$-Glutamyl transpeptidase activity in liver disease: serum elevation is independent of hepatic GGTP activity. Clin. Chim. Acta, 125(3):283-290, 1982. https://doi.org/10.1016/0009-8981(82)90258-3
  25. Irani, K., Xia, Y., Zweier, J.L., Sollott, S.J., Der, C.J., Fearon, E.R., Sundaresan, M., Finkel, T., Goldschmidt-clermont, P.J. Mitogenic signaling mediated by oxidants in Rastransformed fibroblasts. Science, 275: 1649-1652, 1997. https://doi.org/10.1126/science.275.5306.1649
  26. McCord, J.M. Oxygen derived free radicals in postischemic tissue injury. N. Engl. J. Med. 312: 159-163, 1985. https://doi.org/10.1056/NEJM198501173120305
  27. Ip, C., Lisk, D.J. Modulation of phase I and phase II xenobiotic- metabolizing enzymes by selenium-enriched garlic in rats. Nutri. Can. 28: 184-188, 1997. https://doi.org/10.1080/01635589709514573
  28. Castro, J.A., De Ferreyra, E.C., De Castro, C.R., De Fenos, O.M., Sasame, H., Gillette, J.R. Prevention of carbon tetrachloride-induced necrosis by inhibitors of drug metabolism--further studies on their mechanism of action. Biochem. Pharmacol. 23(2):295-302, 1974. https://doi.org/10.1016/0006-2952(74)90420-1
  29. Al-Shabanah, O.A., Alam, K., Nagi, M.N., Al-Rikabi, A.C., Al-Bekairi, A.M. Protective effect of aminoguanidine, a nitric oxide synthase inhibitor, against carbon tetrachloride induced hepatotoxicity in mice. Life Sci. 66(3):265-270, 2000.
  30. Iqbal, S., Vickers, C., Elias, E. Drug metabolism in end-stage liver disease : In vitro activities of some phase I and phase II enzymes. J. Hepatol. 11(1):37-42, 1990. https://doi.org/10.1016/0168-8278(90)90269-W
  31. Mary, J.V., Clifford, R.E., John, J.L. The effect of various types of inducing agents on hepatic microsomal monooxygenase activity in rainbow trout. Toxicol. App. Pharmacol. 59(2):364-374, 1981. https://doi.org/10.1016/0041-008X(81)90208-8
  32. Rama, S.D., Thomas, P., Raymond, F.N. Xenobioticmodulated expression of hepatic glutathione S-transferase genes in primary rat hepatocyte culture. Biochim. Biophy. Acta, 1174(1):43-53, 1993. https://doi.org/10.1016/0167-4781(93)90090-Z
  33. Claudio, J., Helmut, S., Theodorus, P.M.A. Hepatic mercapturic acid formation: involvement of cytosolic cysteinylglycine S-conjugate dipeptidase activity. Biochem. Pharmacol. 56(6):763-771, 1988.