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Acta Biologica Hungarica

, Volume 61, Issue 2, pp 175–190 | Cite as

Hepatocurative Potential of Sesquiterpene Lactones of Taraxacum officinale on Carbon Tetrachloride Induced Liver Toxicity in Mice

  • A. MaheshEmail author
  • R. Jeyachandran
  • L. Cindrella
  • D. Thangadurai
  • V. P. Veerapur
  • D. Muralidhara Rao
Article

Abstract

The hepatocurative potential of ethanolic extract (ETO) and sesquiterpene lactones enriched fraction (SL) of Taraxacum officinale roots was evaluated against carbon tetrachloride (CCl4) induced hepatotoxicity in mice. The diagnostic markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin contents were significantly elevated, whereas significant reduction in the level of reduced glutathione (GSH) and enhanced hepatic lipid peroxidation, liver weight and liver protein were observed in CCl4 induced hepatotoxicity in mice. Post-treatment with ETO and SL significantly protected the hepatotoxicity as evident from the lower levels of hepatic enzyme markers, such as serum transaminase (ALT, AST), ALP and total bilirubin. Further, significant reduction in the liver weight and liver protein in drug-treated hepatotoxic mice and also reduced oxidative stress by increasing reduced glutathione content and decreasing lipid peroxidation level has been noticed. The histopathological evaluation of the liver also revealed that ETO and SL reduced the incidence of liver lesions induced by CC14. The results indicate that sesquiterpene lactones have a protective effect against acute hepatotoxicity induced by the administration of CC14 in mice. Furthermore, observed activity of SL may be due to the synergistic action of two sesquiterpene lactones identified from enriched ethyl acetate fraction by HPLC method.

Keywords

Compositae Taraxacum officinale carbon tetrachloride hepatotoxicity sesquiterpene lactones 

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Notes

Acknowledgements

Authors would like to thank Dr. S. Soosai Raj for plant identification and Dr. G. Mathan for helpful discussion and critical reading of the manuscript.

References

  1. 1.
    Ahmed, B., Alam, T., Varshney, M., Khan, A. S. (2002) Hepatoprotective activity of two plants belonging to the Apiaceae and the Euphorbiaceae family. J. Ethnopharmacol. 79, 313–316.PubMedCrossRefGoogle Scholar
  2. 2.
    Banskota, A. H., Tezuka, Y., Adnyana, I. K., Xiong, Q., Hase, K., Tran, K. Q., Tanaka, K., Saiki, J., Kadota, S. (2000) Hepatoprotective effect of Combretum quadrangulare and its constituents. Biol. Pharm. Bull. 23, 456–460.PubMedCrossRefGoogle Scholar
  3. 3.
    Basil, S. (2003) Carbon tetrachloride-induced lipid peroxidation: Eicosanoid formation and their regulation by antioxidant nutrients. Toxicology 189, 113–127.CrossRefGoogle Scholar
  4. 4.
    Bhandarkar, M. R., Khan, A. (2004) Antihepatotoxic effect of Nymphaea stellata willd. against carbon tetrachloride induced hepatic damage in albino rats. J. Ethnopharmacol. 91, 61–64.PubMedCrossRefGoogle Scholar
  5. 5.
    Bown, D. (1995) Encyclopedia of Herbs and Their Uses. Dorling Kindersley, London, pp. 20–31.Google Scholar
  6. 6.
    Chiej, R. (1984) Encyclopedia of Medicinal Plants. Mac Donald, USA.Google Scholar
  7. 7.
    De Feudis, F. V., Papadopoulos, V., Drieu, K. (2003) Ginkgo biloba extracts and cancer: A research area in its infancy. Fundam. Clin. Pharmacol. 17, 405–417.CrossRefGoogle Scholar
  8. 8.
    Eisisi, A. E., Earnest, D. L., Sipes, I. G. (1993) Vitamin A potentiation of carbon tetrachloride hepa-toxicity: Role of liver macrophages and active oxygen species. Toxicol. Appl. Pharmacol. 119, 295–301.CrossRefGoogle Scholar
  9. 9.
    Ellman, G. L. (1959) Tissue sulphydryl group. Arch. Biochem. Biophys. 82, 70–77.CrossRefGoogle Scholar
  10. 10.
    Esterbauer, H., Cheeseman, K. H. (1990) Determination of aldehydic lipid peroxidation products: Malonaldehyde and 4-hydroxynonenal. Meth. Enzymol. 186, 407–421.PubMedCrossRefGoogle Scholar
  11. 11.
    Foster, S., Duke, J. A. (1990) A Field Guide to Medicinal Plants of Eastern and Central North America. Houghton Mifflin Co., Boston.Google Scholar
  12. 12.
    Goeptar, A. R., Scheerens, H., Vermeulen, N. F. (1995) Oxygen and xenobiotic reductase activities of cytochrome P450. Crit. Rev. Toxicol. 25, 25–65.PubMedCrossRefGoogle Scholar
  13. 13.
    Gueeri, H. (1995) Influence on prolonged ethanol intake on the level and turnover of alcohol and aldehyde dehydrogenase and glutathione. Adv. Exp. Med. Biol. 23, 133–134.Google Scholar
  14. 14.
    Harper, H. A. (1961) The Functions and Tests of the Liver, Review of Physiological Chemistry. Lange Medical Publishers, Los Atlos, CA, pp. 271–283.Google Scholar
  15. 15.
    Jeon, T. I., Hwang, S. G., Lim, B. O. (2003) Extract of Phellinus linteus grown on germinated brown rice suppress liver damage induced by carbon tetrachloride in rats. Biotech. Lett. 25, 2093–2096.CrossRefGoogle Scholar
  16. 16.
    Jin Lee, K., Woo, E. R., Choi, C. Y. (2004) Protective effect of acteoside on carbon tetrachloride-in-duced hepatotoxicity. Life Sci. 74, 1051–1064.CrossRefGoogle Scholar
  17. 17.
    Kadiiska, M. B., Gladen, B. C., Baird, D. D, Dikalov, A. F., Sohal, R. S., Hatch, G. B., Jones, D. P, Mason, R. P., Barret, J. C. (2000) Biomarkers of oxidative stress study: Are plasma antioxidants markers of CC14 poisoning? Free Rad. Biol. Med. 28, 838–845.PubMedCrossRefGoogle Scholar
  18. 18.
    Kaur, G., Jabbar, Z., Athar, M., Alam, M. S. (2006) Punica granatum (pomegranate) flower extract possesses potent antioxidant activity and abrogates Fe-NTA induced hepatotoxicity in mice. Food and Chemical Toxicology 44, 984–993.PubMedCrossRefGoogle Scholar
  19. 19.
    Kisiel, W., Michalska, K. (2006) Matricarin-type guaianolides from Taraxacum bessarabicum and their chemotaxonomic significance. Biochemical Systematics and Ecology 34, 356–359.CrossRefGoogle Scholar
  20. 20.
    Ko, K. M., Ip, S. P., Poon, M. K. T., Wu, S. S, Che, C. T., Ng, K. H. (1995) Effect of lignan enriched Fructus schisandrae extract on hepatic glutathione status in rats: Protection against carbon tetrachloride toxicity. Planta Med. 61, 134–137.PubMedCrossRefGoogle Scholar
  21. 21.
    Launert, E. (1981) Edible and Medicinal Plants. Hamlyn, UK.Google Scholar
  22. 22.
    Liu, J. Y., Chen, C. C., Wang, W. H., Hsu, J. D., Yang, M. Y., Wang, C. J. (2006) The protective effects of Hibiscus sabdariffa extract on CCl4-induced liver fibrosis in rats. Food and Chemical Toxicology 44, 336–343.PubMedCrossRefGoogle Scholar
  23. 23.
    Li-Weber, M., Giaisi, M., Baumann, S., Treiber, M. K., Krammer, P. H. (2002) The anti-inflammatory sesquiterpene lactone, parthenolide suppresses CD95-mediated activation-induced-cell-death in T-cells. Cell Death and Differentiation 9, 1256–1265.PubMedCrossRefGoogle Scholar
  24. 24.
    Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J. (1951) Protein measurement with folin phenol reagent. J. Biol. Chem. 193, 265–275.Google Scholar
  25. 25.
    Mahesh, A., Jeyachandran, R., Cindrella, L., Thangadurai, D., Velayutham, R., Pinheiro de Carvalho, M. A. A. (2008) In: Thangadurai, D., Tang, W., Ramachandran, A., Moraes, I. O., Pinheiro de Carvalho M. A. A. (eds) Biotechnology for Food Environment and Agriculture. Agrobios (India), Jodhpur, pp. 235–251.Google Scholar
  26. 26.
    Mansour, M. A. (2000) Protective effects of thymoquinone and desferrioxamine against hepatotoxicity of carbon tetrachloride in mice. Life Sci. 66, 2583–2591.PubMedCrossRefGoogle Scholar
  27. 27.
    Meijer, D. K. F., Smit, J. W., Muller, M. (1997) Hepatobiliary elimination of cationic drugs: The role of P-glycoproteins and other ATP dependent transporters. Adv. Drug Deliv. Rev. 25, 159–200.CrossRefGoogle Scholar
  28. 28.
    Molander, D. W., Wroblewsk, F., La Due, J. S. (1955) Transaminase compared with cholinesterase and alkaline phosphatase as an index of hepatocellular integrity. Clin. Res. Proc. 3, 20–24.Google Scholar
  29. 29.
    Myagmar, B. E., Shinno, E., Ichiba, T., Aniya, Y. (2004) Antioxidant activity of medicinal herb Rhodococcum vitis-idaea on galactosamine induced liver injury in rats. Phytomedicine 11, 416–423.PubMedCrossRefGoogle Scholar
  30. 30.
    Ohkawa, H., Ohishi, N., Yagi, K. (1979) Assay of lipid peroxides in animal tissue by thiobarbituric acid reaction. Anal Biochem. 95, 351–358.PubMedCrossRefGoogle Scholar
  31. 31.
    Ohta, Y., Nishida, K., Sasaki, E., Kongo, M., Ishiguro, I. (1997) Attenuation of disrupted hepatic active oxygen metabolism with the recovery of acute liver injury in rats intoxicated with carbon tetrachloride. Res. Commun. Mol. Pathol. Pharmacol. 95, 191–207.PubMedGoogle Scholar
  32. 32.
    Ozturk, F., Ucar, M., Ozturk, I. C., Vardi, N., Batcioglu, K. (2003) Carbon tetrachloride induced nephrotoxicity and protective effect of betaine in Sprague-Dawley rats. Urology 62, 353–356.PubMedCrossRefGoogle Scholar
  33. 33.
    Paradise, V., Kollinger, M., Fabre, M., Holstege, A., Poynard, T., Beddosa, P. (1997) In situ detection of lipid peroxidation by products in chronic liver diseases. Hepatology 26, 135–142.CrossRefGoogle Scholar
  34. 34.
    Plaa, G. L., De Lamirande, E., Lewittes, M., Yousef I. M. (1982) Liver cell plasma membrane lipids in manganese-bilirubin induced intrahepatic cholestasis. Biochem. Pharmacol. 31, 3698–3701.PubMedCrossRefGoogle Scholar
  35. 35.
    Recknagel, R. O., Glende Jr., E. A., Dolak, J. A., Waller, R. L. (1989) Mechanisms of carbon tetrachloride toxicity. Pharmacology and Therapeutics 43, 139–154.PubMedCrossRefGoogle Scholar
  36. 36.
    Recknagel, R. O., Glende Jr, E. A., Britton, R. S. (1991) Free radical damage and lipid peroxidation. In: Meeks, R. G. (eds) Hepatotoxicology. CRC Press, Florida, pp. 401–436.Google Scholar
  37. 37.
    Sheweita, S. A., El-Gabar, M. A., Bastawy, M. (2001) Carbon tetrachloride changes the activity of cytochrome P450 system in the liver of male rats: Role of antioxidants. Toxicology 165, 217–224.PubMedCrossRefGoogle Scholar
  38. 38.
    Simmons, J. E., Yang, R. S., Berman, E. (1995) Evaluation of the nephrotoxicity of complex mixtures containing organics and metals: Advantages and disadvantages of the use of real-world complex mixtures. Environ. Health Perspect. 103, 67–71.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Siyuan, Z., Yen-Kim, W., Choon-Nam, O., Han-Ming, S. (2005) Anti-cancer potential of sesquiterpene lactones: Bioactivity and molecular mechanisms. Current Medicinal Chemistry 5, 239–249.Google Scholar
  40. 40.
    Takeoka, G. R., Dao, L. T. (2003) Antioxidant constituent of almond (Prunus dulcis (Mill.) D. A. Webb.) hulls. J. Agric. Food Chem. 51, 496–501.PubMedCrossRefGoogle Scholar
  41. 41.
    Tang, X., Gao, J., Wang, Y., Fan, Y. M., Xu, L. Z., Zhao, X. N., Xu, Q., Qian, Z. M. (2006) Effective protection of Terminalia catappa L. leaves from damage induced by carbon tetrachloride in liver mitochondria. J. Nutr. Biochem. 17, 177–182.PubMedCrossRefGoogle Scholar
  42. 42.
    Vaca, C. E., Wilhelm, J., Harms-Rihsdahl, M. (1988) Interaction of lipid peroxidation product with NNA. Mutat. Res. Rev. Genet. Toxicol. 195, 137–149.CrossRefGoogle Scholar
  43. 43.
    Weber, L. W. D., Bull, M., Stampfl, A. (2003) Hepatotoxicity and mechanism of action of haloal-kanes: Carbon tetrachloride as a toxicological model. Crit. Rev. Toxicol. 33, 105–136.PubMedCrossRefGoogle Scholar
  44. 44.
    Williams, A. T., Burk, R. F. (1990) Carbon tetrachloride hepatotoxicity: An example of free radical-mediated injury. Semin. Liver Dis. 10, 279–284.PubMedCrossRefGoogle Scholar
  45. 45.
    Zimmerman, H. J., Seef L. B. (1970) Enzymes in hepatic disease. In: Goodley, E. L. (ed.), Diagnostic Enzymology. Philadelphia, pp. 1–38.Google Scholar

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© Akadémiai Kiadó, Budapest 2010

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors and Affiliations

  • A. Mahesh
    • 1
    • 2
    Email author
  • R. Jeyachandran
    • 2
  • L. Cindrella
    • 3
  • D. Thangadurai
    • 4
  • V. P. Veerapur
    • 5
  • D. Muralidhara Rao
    • 6
  1. 1.Department of Plant Genetics, Institute of Plant Sciences, AROThe Volcani CenterBet-DaganIsrael
  2. 2.Department of Plant Biology and Plant BiotechnologySt. Joseph’s CollegeTiruchirappalliIndia
  3. 3.Department of ChemistryNational Institute of TechnologyTiruchirappalliIndia
  4. 4.Department of BotanyKarnatak UniversityDharwadIndia
  5. 5.Department of Pharmaceutical ChemistrySET College of PharmacyDharwadIndia
  6. 6.Department of BiotechnologySri Krishnadevaraya UniversityAnantapurIndia

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