2nd Department of Medicine, Semmelweis University, Szentkirályi u. 46, H-1088, Budapest, Hungary
Search for other papers by János Fehér in
Current site
Google Scholar
PubMed
Search for other papers by Gabriella Lengyel in
Current site
Google Scholar
PubMed
Abstract
In the treatment of chronic liver diseases an adequate therapy can be chosen only in the knowledge of the pathogenetic processes. In liver diseases caused by oxidative stress (alcoholic and non-alcoholic fatty liver and steatohepatitis, drug- and chemical-induced hepatic toxicity) the antioxidant medicines such as silymarin, in chronic hepatitis caused by hepatitis B and hepatitis C virus the combined pegylated interferon and nucleoside analogue treatments are the primary therapeutic modalities of choice. The main effects of silymarin: it exerts membrane-stabilising and antioxidant activity, it promotes hepatocyte regeneration, it reduces inflammatory reaction, and it inhibits fibrinogenesis in the liver. These results have been established by experimental and clinical trials. According to open studies the long-term administration of silymarin significantly increased survival time of patients with alcoholinduced liver cirrhosis. Recently it has been demonstrated that high-dose silibinin infusion treatment could significantly reduce viral load of hepatitis C viruses following four weeks of application. Based on the results of studies using methods of molecular biology, silymarin can significantly reduce tumour cell proliferation, angiogenesis as well as insulin resistance. These results support the administration of silymarin preparations in the treatment of patients with chronic liver diseases, especially alcoholic and non-alcoholic steatohepatitis in the current clinical practice and, as it can be expected, also in the future. In some neoplastic diseases they can be administered as adjuvant therapy as well.
-
[1]. J. Feher G. Csomos A. Vereckei 1987 Free radical reaction in biology and medicine Springer Verlag Berlin, Heidelberg, New York.
-
[2]. J. Fehér G. Lengyel 2001 Hepatology Medicina Könyvkiadó Budapest.
-
[3]. P. Ferenci B. Dragosics H. Dittrich et al.1989 Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver J. Hepatol. 9 105–113.
-
[4]. M. P. Manns J. G. McHutchison S. C. Gordon et al.2001 Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomized trial Lancet 358 958–965.
-
[5]. M. W. Fried M. L. Shiffman K. R. Reddy et al.2002 Peginterferon alfa-2a plus ribavirin for chronic hepatitis C infection N. Engl. J. Med. 347 975–982.
-
[6]. S. J. Hadziyannis H. Sette T. R. Morgan et al.2004 Peginterferon alfa-2a (40 kilodaltons) and ribavirin combination therapy in chronic hepatitis C: randomized study of the effect of treatment duration and ribavirin dose Ann. Intern. Med. 140 346–355.
-
[7]. V. Fintelmann A. Albert 1980 Nachweis der therapeutischen Wirksamkeit von Legalon bei toxischen Lebererkrankungen im Doppelblindversuch Therapiewoche 30 5589–5594.
-
[8]. J. Fehér G. Deák Gy. Müzes et al.1989 Liver-protective action of silymarin therapy in chronic alcoholic liver diseases Orv. Hetil. 130 2723–2727.
-
[9]. H. Koch G. Zinsberger 1980 Löslichkeitsparameter von Silybin, Silydianin und Silychristin Arch Pharm. 313 526–533.
-
[10]. K. Hruby G. Csomos M. Fuhrmann et al.1983 Chemotherapy of Amanita phalloides poisoning with intravenous silibinin Hum. Toxicol. 2 183–195.
-
[11]. Negi, A. S., Kumar, J. K., Luqman, S. et al.: Recent Advances in Plant Hepatoprotectives: A Chemical and Biological Profile of Some Important Leads., Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/med.20115.
-
[12]. Gy. Müzes Gy. Deák I. Láng et al.1990 Effect of silimarin (Legalon) therapy on the antioxidant defense mechanism and lipid peroxidation in alcoholic liver disease (double-blind protocol) Orv. Hetil. 131 863–866.
-
[13]. J. Fehér I. Láng K. Nékám et al.1988 Effect of free radical scavengers on superoxide dismutase (SOD) enzyme in patients with alcoholic cirrhosis Acta Med. Hung. 45 265–276.
-
[14]. F. Lirussi L. Okolicsanyi 1992 Cytoprotection in the nineties: experience with ursodeoxycholic acid and silymarin in chronic liver disease Acta Physiol. Hung. 80 363–367.
-
[15]. A. Pares R. Planas M. Torres et al.1998 Effects of silymarin on alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomized and multicenter trial J. Hepatol. 28 615–621.
-
[16]. K. Flora M. Hahn H. Rosen et al.1998 Milk Thistle (Silybum marianum) for the therapy of liver disease Am. J. Gastro enterol. 93 139–143.
-
[17]. G. Lengyel Z. Tulassay 2006 Antioxidant therapy in chronic liver diseases Orv. Hetil. 147 1113–1118.
-
[18]. F. Lirussi A. Beccarello G. Zanette et al.2002 Silybin-beta-cyclodextrin in the treatment of patients with diabetes mellitus and alcoholic liver disease. Efficacy study of a new preparation of an antioxidant agent Diabetes Nutr. Metab. 15 222–231.
-
[19]. A. Pár E. Róth G. Rumi Jr. et al.2000 Oxidative stress and antioxidant defense in alcoholic liver disease and chronic hepatitis C Orv. Hetil. 141 1655–1659.
-
[20]. C. Levy L. D. Seeff K. D. Lindor 2004 Use of herbal supplements for chronic liver disease Clin. Gastro enterol. Hepatol. 2 947–956.
-
[21]. J. A. Salomon M. C. Weinstein J. K. Hammitt et al.2003 Cost-effectiveness of treatment for chronic hepatitis C infection in an evolving patient population JAMA 290 228–237.
-
[22]. R. Saller J. Melzer J. Reichling et al.2007 An updated systematic review of the pharmacology of silymarin Forsch. Komplementarmed. 14 70–80.
-
[23]. Y. C. Kim E. J. Kim E.D. Lee et al.2003 Comparative bioavailability of silibinin in healthy male volunteers Int. J. Clin. Pharmacol. Ther. 41 593–596.
-
[24]. K. E. Mayer R. P. Myers S. S. Lee 2005 Silymarin treatment of viral hepatitis: a systematic review J. Viral Hepat. 12 559–567.
-
[25]. R. Huber I. Futter R. Ludtke 2005 Oral silymarin for chronic hepatitis C — a retrospective analysis comparing three dose regimens Eur. J. Med. Res. 10 68–70.
-
[26]. S. J. Polyak C. Morishima M. C. Shuhart et al.2007 Inhibition of T-inflammatory cytokines, hepatocyte NF-_B signaling, and HCV infection by standardized silymarin Gastro enterol. 132 1925–1936.
-
[27]. K. E. Mayer R. P. Myers S. S. Lee 2005 Silymarin treatment of viral hepatitis: a systematic review J.Viral Hepatol. 12 559–567.
-
[28]. A. Rambaldi B. P. Jacobs G. Iaquinto et al.2005 Milk thistle for alcoholic and/or hepatitis B or C liver diseases: a systematic Cochrane hepato-biliary group review with meta-analyses of randomized clinical trials Am. J. Gastro enterol. 100 2583–2591.
-
[29]. A. Gordon D.A. Hobbs D.S. Bowden et al.2006 Effects of silybum marianum on serum hepatitis C virus RNA, alanine aminotransferase levels and well-being in patients with chronic hepatitis C J. Gas tro enterol. Hepatol. 21 275–280.
-
[30]. L. B. Seeff T.M. Curto Gy. Szabo the HALT-C Trial Group 2008 Herbal Product Use by Persons Enrolled in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALTC) Trial Hepatol. 47 605–612.
-
[31]. M. Romero-Gómez 2006 Insulin resistance and hepatitis C World J. Gastro enterol. 12 7075–7080.
-
[32]. P. Ferenci T. M. Scherzer A. Hofer et al.2008 Silibinin is a potent antiviral agent in patients with chronic hepatitis C not responding to antiviral combination therapy J. Hepatol. 48 Suppl.2 28.
-
[33]. Ferenci, P., Scherzer, T. M., Kerschner, H. et al.: Silibinin Is a Potent Antiviral Agent in Patients With Chronic HCV not Responding to Pegylated Interferon/Ribavirin Therapy. Gastro — enterology, 2008, (open access, in press).
-
[34]. S. Beckmann-Knopp S. Rietbrock R. Weyhenmeyer et al.2000 Inhibitory effects of silibinin on cytochrome P-450 enzymes in human liver microsomes Pharmacol. Toxicol. 86 250–256.
-
[35]. R. Saller R. Brignoli J. Melzer et al.2008 An Updated Systematic Review with Meta-Analysis for the Clinical Evidence of Silymarin Forsch Komplementärmed. 15 9–20.
-
[36]. O. P. Gupta S. Sing S. Bani et al.2000 Anti-inflammatory and anti-arthritic activities of silymarin acting through inhibition of 5-lipoxygenase Phytomed. 7 21–24.
-
[37]. G. Ramakrishnan S. Jagan T. A. Augustine et al.2008 Silymarin downregulates COX-2 expression and attenuates hyperlipidemia during NDEA-induced rat hepatocellular carcinoma Mol Cell Biochem. 313 53–61.
-
[38]. P. Kosina P. Maurel J. Ulrichova et al.2005 Effect of silybin and its glycosides on the expression of cytochromes P450 1A2 and 3A4 in primary cultures of human hepatocytes J. Biochem. Mol. Toxicol. 19 149–153.
-
[39]. S. R. Volate D. M. Davenport S. J. Muga et al.2005 Modulation of aberrant crypt foci and apoptosis by dietary herbal supplements (quercetin, curcumin, silymarin, ginseng, and rutin) Carcinogen. 26 1450–1456.
-
[40]. C. Agarwal R. Sing S. Dhanalakshmi et al.2003 Silibinin upregulates the expression of cyclindependent kinase inhibitors and causes cell cycle arrest and apoptosis in human colon carcinoma HT-29 cells Oncogene 22 8271–8282.
-
[41]. R. P. Singh M. Gu R. Agarwal 2008 Silibinin Inhibits Colorectal Cancer Growth by Inhibiting Tumor Cell Proliferation and Angiogenesis Cancer Res. 68 2043–2050.
-
[42]. S. C. Chu H. L. Chiou P. N. Chen et al.2004 Silibinin inhibits the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2 Mol. Carcinogen. 40 143–149.
-
[43]. N. A. El-Shitany S. El-Haggar K. El-desoky 2008 Silymarin prevents adriamycin-induced cardiotoxicity and nephrotoxicity in rats Food and Chem. Toxicol. 46 2422–2428.
-
[44]. Ramasamy, K., Agarwal, R.: Multitargeted therapy of cancer by silymarin, Cancer Lett., 2008. doi:10.1016/j.canlet.2008.03.053 (Open access, in press).
-
[45]. R. P. Singh G. U. Mallikarjuna G. Sharma et al.2004 Oral silibinin inhibits lung tumor growth in athymic nude mice and forms a novel chemocombination with doxorubicin targeting nuclear factor nB-mediated inducible chemoresistance Clin. Cancer Res. 10 8641–8647.
-
[46]. S. H. Yang J. K. Lin W. S. Chen et al.2003 Anti-angiogenic effect of silymarin on colon cancer LoVo cell line J. Surg. Res. 113 133–138.
-
[47]. R. P. Singh M. Gu R. Agarwal 2008 Silibinin Inhibits Colorectal Cancer Growth by Inhibiting Tumor Cell Proliferation and Angiogenesis Cancer Res. 68 2043–2050.
-
[48]. F. S. Hogan N.K. Krishnegowda M. Mikhailova et al.2007 Flavonoid, Silibinin, Inhibits Proliferation and Promotes Cell-Cycle Arrest of Human Colon Cancer1 J. Surg. Res. 143 58–65.
-
[49]. E.A. Soria A. E. Eynard P. E. Quiroga et al.2007 Differential effects of quercetin and silymarin on arsenite-induced cytotoxicity in two human breast adenocarcinoma cell lines Life Sci. 81 1397–1402.
-
[50]. G. Deep N. H. Oberlies D.J. Kroll et al.2008 Identifying the differential effects of silymarin constituents on cell growth and cell cycle regulatory molecules in human prostate cancer cells Int. J. Cancer 123 41–50.
-
[51]. P. R. Davis-Searles Y. Nakanishi N. C. Kim et al.2005 Milk thistle and prostate cancer: differential effects of pure flavonolignans from Silybum marianum on antiproliferative end points in human prostate carcinoma cells Cancer Res. 65 4448–4457.
-
[52]. R. P. Singh A. Tyagi G. Sharma et al.2008 Oral silibinin inhibits in vivo human bladder tumor xenograft growth involving down-regulation of survivin Clin. Cancer Res. 14 300–308.
-
[53]. S. K. Katiyar 2005 Silymarin and skin cancer prevention: anti-inflammatory, antioxidant and immunomodulatory effect (review) Int. J. Oncol. 26 169–176.
-
[54]. H. Ligeret A. Brault D. Vallerand et al.2008 Antioxidant and mitochondrial protective effects of silibinin in cold preservation-warm reperfusion liver injury J. Ethnopharmacol. 115 507–514.
-
[55]. Senturk, H., Kabay, S., Bayramoglu, G. et al.: Silymarin attenuates the renal ischemia/reperfusion injury-induced morphological changes in the rat kidney World J. Urol., DOI 10.1007/s00345-008-0256-1 (Open access, in press).
| Clinical and Experimental Medical Journal | |
|---|---|
| Language | English |
| Size | |
| Year of Foundation |
2007 |
| Publication Programme |
ceased |
| Volumes per Year |
|
| Issues per Year |
|
| Publisher | Akadémiai Kiadó |
| Publisher's Address |
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245 |
| Responsible Publisher |
Chief Executive Officer, Akadémiai Kiadó |
| ISSN | 2060-6249 (Print) |
| ISSN | 2060-968X (Online) |
Monthly Content Usage
| Abstract Views | Full Text Views | PDF Downloads | |
|---|---|---|---|
| Dec 2024 | 33 | 0 | 0 |
| Jan 2025 | 55 | 0 | 0 |
| Feb 2025 | 71 | 0 | 0 |
| Mar 2025 | 72 | 0 | 0 |
| Apr 2025 | 23 | 0 | 0 |
| May 2025 | 9 | 0 | 0 |
| Jun 2025 | 0 | 0 | 0 |
1st Congress of Fatty Liver and Metabolic Syndrome
From Basic Science to the Clinical Praxis
Copyright Akadémiai Kiadó AKJournals is the trademark of Akadémiai Kiadó's journal publishing business branch.