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DOI: 10.1055/s-2000-9603
© Georg Thieme Verlag Stuttgart · New York
Panax vietnamensis Protects Mice Against Carbon Tetrachloride-Induced Hepatotoxicity without any Modification of CYP2E1 Gene Expression
Publication History
December 28, 1999
May 27, 2000
Publication Date:
31 December 2000 (online)
Abstract
In order to explore the effect of Panax vietnamensis on carbon tetrachloride-induced hepatotoxicity, mice were pretreated for 7 days with either crude extract or total saponins. Crude extract and total saponins dramatically decreased carbon tetrachloride-induced increase of serum GSTα level (- 50.0 %, - 49.5 % respectively). Serum AST level was significantly decreased only with total saponins (- 52.2 %) and ALT level was slightly modified. In vitro experiments shown that both preparations at high concentrations (> 2000 μg/ml) are able to inhibit CYP2E1 enzymatic activity in mouse and human microsomes. However, we did not observe any modification of Cyp2e1 gene expression (enzymatic activity, protein and mRNA levels) in mice treated with either crude extract or total saponins. Taken together, these data demonstrated that Panax vietnamensis could be used as an hepatoprotectant. However, the mechanism of action is not associated with CYP2E1 expression, as previously suggested in vitro in rat for total saponins from Panax ginseng.
Key words
Panax vietnamensis - Araliaceae - hepatoprotection - carbon tetrachloride - CYP2E1 - mice
References
- 1 Hikino H, Kiso Y, Kinouchi J, Sanada S, Shoji J. Antihepatotoxic actions of ginsenosides from Panax ginseng roots. Planta Medica. 1985; 57 62-4
- 2 Jeong T C, Kim H J, Park J I, Ha C S, Park J D, Kim S I, Roh J K. Protective effects of red ginseng saponins against carbon tetrachloride-induced hepatotoxicity in Sprague Dawley rats. Planta Medica. 1997; 63 136-40
- 3 Liu J, Liu Y, Klaassen C D. The effect of Chinese hepatoprotective medicines on experimental liver injury in mice. Journal of Ethnopharmacology. 1994; 42 183-91
- 4 Song J C, Liu J, Zhang Y, Zhan Q Z, Zhou J, Wu M Z. Effect of total saponins of Panax notoginseng on DNA and protein metabolism in CCl4 intoxicated mice. Bulletin of Pharmacy Sinica. 1982; 17 67-9
- 5 Kim H J, Chun Y J, Park J D, Kim S I, Roh J K, Jeong T C. Protection of rat liver microsomes against carbon tetrachloride-induced lipid peroxidation by red ginseng saponin through cytochrome P450 inhibition. Planta Medica. 1997; 63 415-8
- 6 Johansson I, Ingelman-Sundberg M. Carbon tetrachloride-induced lipid peroxidation dependent on an ethanol-inducible form of rabbit liver microsomal cytochrome P-450. FEBS Letters. 1985; 183 265-9
- 7 Wong F W, Chan W Y, Lee S S. Resistance to carbon tetrachloride-induced hepatotoxicity in mice which lack CYP2E1 expression. Toxicology and Applied Pharmacology. 1998; 153 109-18
- 8 Duc N M, Kasai R, Ohtani K, Ito A, Yamasaki K, Nham T N, Tanaka O. New saponins from Vietnamese ginseng: highlights on biogenesis of dammarane triterpenoids. Advanced in Experimental Medecine Biology. 1996; 404 129-49
- 9 Duc N M, Nham N T, Kasai R, Ito A, Yamasaki K, Tanaka O. Saponins from Vietnamese ginseng, Panax vietnamensis Ha et Grushv. collected in central Veitnam. Chemical and Pharmaceutical Bulletin. 1993; 41 2010-4
- 10 van der Hoeven T A, Coon M J. Preparation and properties of partially purified cytochrome P-450 and reduced nicotinamide adenine dinucleotide phosphate-cytochrome P-450 reductase from rabbit liver microsomes. Journal of Biological Chemistry. 1974; 249 6302-10
- 11 Koop D R, Laethem C L, Tierney D J. The utility of p-nitrophenol hydroxylation in P450IIE1 analysis. Drug Metabolism Reviews. 1989; 20 541-51
- 12 Villard P H, Seree E M, Re J L, De Meo M, Barra Y, Attolini L, Dumenil G, Catalin J, Durand A, Lacarelle B. Effects of tobacco smoke on the gene expression of the Cyp1a, Cyp2b, Cyp2e, and Cyp3a subfamilies in mouse liver and lung: relation to single strand breaks of DNA. Toxicology and Applied Pharmacology. 1998; 148 195-204
- 13 Clarke H, Egan D A, Heffernan M, Doyle S, Byrne C, Kilty C, Ryan M P. Alpha-glutathione s-transferase (alpha-GST) release, an early indicator of carbon tetrachloride hepatotoxicity in the rat. Human and Experimental Toxicology. 1997; 16 154-7
- 14 Diaz Gomez M I, de Castro C R, D'Acosta N, de Fenos O M, de Ferreyra E C, Castro J A. Species differences in carbon tetrachloride-induced hepatotoxicity: the role of CCl4 activation and of lipid peroxidation. Toxicology and Applied Pharmacology. 1975; 34 102-14
- 15 Huong N T, Matsumoto K, Kasai R, Yamasaki K, Watanabe H. In vitro antioxidant activity of Vietnamese ginseng saponin and its components. Biological and Pharmaceutical Bulletin. 1998; 21 978-81
Prof. Bruno Lacarelle
Laboratory of Toxicology (EA2194)
School of Pharmacy
Univ. Méditerranée
27 Bd. Jean Moulin
13385 Marseilles Cedex 5
France
Email: bruno.lacarelle@pharmacie.univ-mrs.fr
Phone: Phone and Fax: (33) 491835608