Korean Journal of Pharmacognosy (생약학회지)

The Korean Society of Pharmacognosy (한국생약학회)
권호 표지

Cytoprotective Effects of Natural Flavonoids on Carbon Tetrachloride-Induced Toxicity in Primary Cultures of Rat Hepatocytes

사염화탄소로 유도한 일차 배양 간세포 독성에서 Flavonoid류의 세포보호 효과

  • Published : 2005.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Protective effects of various natural flavonoids on carbon tetrachloride $(CCl_4)-induced$ hepatotoxicity were investigated in primary cultured rat hepatocytes. Some of these flavonoids decreased the ALT and LDH releases induced by $CCl_4$ in A dose-dependent manner. Neohesperidin, hesperetin, baicalin, baicalein and quercetin inhibited $CCl_4-induced$ alanine aminotransferase (ALT) release. In addition, quercetin, quercitrin, neohesperidin, baicalin, baicalein and naringin reduced $CCl_4$ induced lactate dehydrogenase (LDH) leakage. Among these flavonoids, quercitrin, quercetin, baicalin and baicalein possessed potent protective effects and were selected for the further investigation on lipid peroxidation. These four flavonoids inhibited dose dependently $CCl_4-induced$ lipid peroxidation. Especially, the protective effects of quercetin and baicalein were similar to silybin as a well-known hepatoprotective agent. These results suggest that these four flavonoids have significant cytoprotective effects and possibility of therapeutic effect on chemical-induced liver diseases.

Keywords

References

  1. Hikino, H. (1985) Antihepatotoxic activity of crude drugs. Yakugaku Zasshi 105: 109-118
  2. Gilman, A. G. (1985) Carbon tetrachloride. The pharmacological basis of therapeutics 7: 1635-1636
  3. 보건복지부 통계자료(2002)
  4. Markovits, J., Linassier, C., Fosse, P., Couprie, J., Pierre, J., Jacquemin-Sablon, A., Saucier, J. M., Le Pecq, J. B., and Larsen, A. K. (1989) Inhibitory effects of the tyrosine kinase inhibitor genistein on mammalian DNA topoisomerase II. Cancer Res. 49: 5111-5117
  5. Tricoli, J. V., Sahai, B. M., McCormick, P. J., Jarlinski, S. J., Bertram, J. S., and Kowalski, D. (1985) DNA topoisomerase I and II activities during cell proliferation and the cell cycle in cultured mouse embryo fibroblast (C37 lOT 1/2) cells. Exp. cell. Res. 158: 1-14 https://doi.org/10.1016/0014-4827(85)90426-4
  6. Gao, Z., Huang, K., Yang, X., and Xu, H. (1999) Free radical scavenging and antioxidant activities of flavonoids extracted from the radix of Scutellaria baicalensis Georgi. Biochim. Biophys. Acta. 1472: 643-650 https://doi.org/10.1016/S0304-4165(99)00152-X
  7. Middlenton, Jr. E., and Kandaswami, C. (1992) Effects of flavonoids on immune and inflammatory cell functions. Biochemical Pharmacol. 43: 1167-1179 https://doi.org/10.1016/0006-2952(92)90489-6
  8. Miocinovic, R., McCabe, N. P., Keck, R. W., Jankun, J., Hampton, J. A., and Selman, S. H. (2005) In vivo and in vitro effect of baicalein on human prostate cancer cells. Int. J Oncol. 26: 241-246
  9. Gu, Z. Q., Sun, Y H., Xu, C. L., and Liu, Y. (2005) Study of baicalin in inducing prostate cancer cell line DU145 apoptosis in vitro. Zhongguo Zhong Yao Za Zhi. 30: 63-66
  10. Martinez-Florez, S., Gutierrez-Femandez, B., Sanchez-Campos, S., Gonzalez-Gallego, J., and Tunon, M. J. (2005) Quercetin attenuates Nuclear Factor-{kappa} B activation and nitric oxide production in Interleukin-I {beta}-activated rat hepatocytes. J. Nutr. 135: 1359-1365
  11. Lee, H. U., Bae, E. A., and Kim, D. H. (2005) Hepatoprotective effect of tectoridin and tectorigenin on tert-butyl hyperoxide-induced liver injury. J. Pharmacol. Sci. 97: 541544
  12. Liu, Y., Zhang, Y. M., Song, D. F., and Cui, H. B. (2005) Effect of apoptosis in human breast cancer cells and its probable mechanisms by genistein. Wei Sheng Yan Jiu. 34: 67-69
  13. Ratty, A. K. and Das, N. P. (1988) Effects of flavonoids on nonenzymatic lipid peroxidation: Structure-activity relationship. Biochem. Mod Metab. Biol. 39: 69-79 https://doi.org/10.1016/0885-4505(88)90060-6
  14. 일양약품 등(1993) 고동균류로서 간장질환치료제의 개발
  15. Seglen, P. O. (1976) Preparation of isolation rat liver cell. Methods cell Biol. 13: 29-83 https://doi.org/10.1016/S0091-679X(08)61797-5
  16. Albano, E., Carini, R., Parola, M., Bellomo, G, Goria-Gatti, L., Poli, G, and Dianzani, M. U. (1989) Effects of carbon tetrachloride on calcium homeostasis: A critical reconsideration. Biochemical Pharmacol. 38: 2719-2725 https://doi.org/10.1016/0006-2952(89)90559-5
  17. Bataller, R., Schwabe, R. F., Choi, Y. H., Yang, L., Paik, Y. H., Lindquist, J., Qian, T., Schoonhoven, R., Hagedorn, C. H., Lemasters, J. J., and Brenner, D. A. (2003) NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis. J. Clin. Invest. 112:1383-1394
  18. Gilani, A. H., Janbaz, K. H., and Shah, B. H. (1997) Quercetin exhibits hepatoprotective activity in rats. Biochem. Soc. Trans. 25: S619
  19. Lee, E. S., Lee, H. E., Shin, J. Y., Yoon, S., and Moon, J. O. (2003) The flavonoid quercetin inhibits dimethylnitrosamineinduced liver damage in rats. J. Pharm. Pharmacol. 55: 1169-1174 https://doi.org/10.1211/0022357021396
  20. Jang, S. I., Kim, H. J., Hwang, K. M., Jekal, S. J., Pae, H. O., Choi, B. M., Yun, Y. G., Kwon, T. O., Chung, H. T., and Kim, Y. C. (2003) Hepatoprotective effect of baicalin, a major flavone from Scutellaria radix, on acetaminopheninduced liver injury in mice. Immunopharmacol Immunotoxicol. 25: 585-594 https://doi.org/10.1081/IPH-120026443
  21. Glende, E. A. and Recknagel, R. O. (1992) Phospholipase $A_2$ activation and cell injury in isolated rat hepatocytes exposed to bromotrichloromethane, chloroform, and 1, l-dichloroethylene as compared to effects of carbon tetrachloride. Toxicol. Appl. Pharmacol. 113: 159-162 https://doi.org/10.1016/0041-008X(92)90021-J