medigraphic.com
Órgano Oficial de la Asociación Mexicana de Hepatología

2007, Number 1

<< Back Next >>

Ann Hepatol 2007; 6 (1)

Genistein decreases liver fibrosis and cholestasis induced by prolonged biliary obstruction in the rat

Leija SA, Ocampo G, Garrido FG, Reyes-Esparza J, Rodríguez-Fragoso L

Language: English
References: 44
Page: 41-47
PDF size: 254.16 Kb.


Text Extraction

Fibrosis accompanies most chronic liver disorders and is a major factor contributing to hepatic failure. Therefore, the need for an effective treatment with the aim of modifying the clinical course of this disease is evident. The aim of this work is to determine whether genistein, which has been shown to modulate the physiology and pathophysiology of liver, is able to decrease experimental liver fibrosis and cholestasis. In male Wistar rats, the common bile duct was ligated. Administration of genistein (5 μg rat-1, day-1, p.o.) began four weeks after biliary obstruction and continued for a further four weeks. The liver was used for histological and ultrastructural analysis and for collagen quantification (hydroxyproline content). The degradation of Matrigel® and collagen type I was determined in homogenized liver. Bilirubins and enzyme activities were measured in serum. Genistein was able to improve normal liver histology, ultrastructure, collagen content, and biochemical markers of liver damage. It also increased Matrigel® and collagen type I degradation. In summary, the present report shows that genistein inhibits the fibrosis and cholestasis induced by prolonged biliary obstruction in the rat. Genistein has therapeutic potential against liver fibrosis.


REFERENCES

  1. De Franchis R, Hadengue A, Lau G, Lavanchy D, Lok A, McIntyre N, Mele A, Paumgartner G, Pietrangelo A, Rodes J, Rosenberg W, Valla D. EASL International Consensus Conference on Hepatitis B. 13-14 September, 2002 Geneva, Switzerland. Consensus statement (long version). J Hepatol 2003; 39: S3-25.

  2. Alberti A, Chemello L, Benvegnu L. Natural history of hepatitis C. J Hepatol 1999; 31: 17-24.

  3. Mendez-Sanchez N, Chavez-Tapia NC, Uribe M. Hepatocyte transplantation for acute and chronic liver diseases. Ann Hepatol 2005; 4: 212-215.

  4. Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology 2003; 37: 1202-1219.

  5. Knodell RG, Ishak KG, Black WC, Chen TS, Craig R, Kaplowitz N, Kiernan TW, Wollman J. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1981; 1: 431-435.

  6. Ishak KG. Chronic hepatitis: morphology and nomenclature. Mod Pathol 1994; 7: 690-713.

  7. Tilg H, Kaser A, Moschen AR. How to modulate inflammatory cytokines in liver diseases. Liver International 2006; 26: 1029-1039.

  8. Friedman SL. Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J Biol Chem 2000; 275: 2247-2250.

  9. Wu J, Zern MA. Hepatic stellate cells: a target for the treatment of liver fibrosis. J Gastroenterol 2000; 35: 665-672.

  10. Polkowski K, Mazurek AP. Biological properties of genistein. A review of in vitro and in vivo data. Acta Pol Pharm 2000; 57: 135-155.

  11. Goldwyn S, Lazinsky A, Wei H. Promotion of health by soy isoflavones: efficacy, benefit and safety concerns. Drug Metabol & Drug Interact 2000; 17: 261-289.

  12. Caldarelli A, Diel P, Vollmer G. Effect of phytoestrogens on gene expression of carbonic anhydrase II in rat uterus and liver. J Steroid Biochem Mol Biol 2005; 97: 251-6.

  13. Wang HK. The therapeutic potential of flavonoids. Expert Opin Investig Drugs 2000; 9: 2103-2119.

  14. Lee YM, Choi JS, Kim MH, Jung MH, Lee YS, Song J. Effects of dietary genistein on hepatic lipid metabolism and mitochondrial function in mice fed high-fat diets. Nutrition 2006; 22: 956-964.

  15. Atherton KM, Mutch E, Ford D. Metabolism of the soyabean isoflavone daidzein by CYP1A2 and the extra-hepatic CYPs 1A1 and 1B1 affects biological activity. Biochem Pharmacol 2006; 72: 624-631.

  16. Ae Park S, Choi MS, Cho SY, Seo JS, Jung UJ, Kim MJ, Sung MK, Park YB, Lee MK. Genistein and daidzein modulate hepatic glucose and lipid regulating enzyme activities in C57BL/KsJ-db/db mice. Life Sci 2006; 79:1207-1213.

  17. Zhao JH, Arao Y, Sun SJ, Kikuchi A, Kayama F. Oral administration of soy-derived genistin suppresses lipopolysaccharide-induced acute liver inflammation but does not induce thymic atrophy in the rat. Life Sci 2006; 78:812-819.

  18. Tikkanen MJ, Wahala K, Ohala S, Vihma V, Adlercreutz H. Effect of soybean phytoestrogen intake on low-density lipoprotein oxidation resistance. Proc Natl Acad Sci USA 1998; 95: 3106-10.

  19. Geis RB, Diel P, Degen GH, Vollmer G. Effects of genistein on the expression of hepatic genes in two rat strains (Sprague-Dawley and Wistar). Toxicol Lett 2005; 157: 21-29.

  20. Fang YC, Chen BH, Huang RF, Lu YF. Effect of genistein supplementation on tissue genistein and lipid peroxidation of serum, liver and low-density lipoprotein in hamsters. J Nutr Biochem 2004; 15:142-148.

  21. Kang LP, Qi LH, Zhang JP, Shi N, Zhang M, Wu TM, Chen J. Effect of genistein and quercetin on proliferation, collagen synthesis, and type I procollagen mRNA levels of rat hepatic stellate cells. Acta Pharmacol Sin 2001; 22: 793-796.

  22. Badria FA, Dawidar AA, Houssen WE, Shier WT. In vitro study of flavonoids, fatty acids, and steroids on proliferation of rat hepatic stellate cells. Z Naturforsch [C]. 2005; 60: 139-142.

  23. Qi LH, Kang LP, Zhang JP, Shi N, Zhang M, Wu TM. Antifibrotic effects of genistein and quercetin in vitro. Yao Xue Xue Bao. 2001; 36: 648-651.

  24. Rodríguez FL, Campos GF, Ocampo MG, Leija A, Garrido FG, Reyes EJ. Genistein decreases liver fibrosis and cholestasis from bile duct ligated rats. The FASEB Journal 2004; 19: A437 (abstract).

  25. Committee on Care and Use of Laboratory Animals of the Institute for Laboratory Animal Resources, Commission on Life Sciences, National Research Council: Guide for the Care and Use of Laboratory Animals. Publication 86-23, 18 and the Animal Welfare Act of 1966, as amended.

  26. Rojkind M, Gonzalez P. An improved method for determining specific radioactivities of proline-14C in collagen and non collagenous protein. Anal Biochem 1974; 57: 1-7.

  27. Nethery A, Lyons JG, O´grady RL. A spectrophotometric collagenase assasy. Anal Biochem 1986; 159: 390-395.

  28. Bataller R, Brenner DA. Liver fibrosis. J Clin Invest 2005; 115: 209-218.

  29. Schuppan D, Ruehl M, Somasundaram R, Hahn EG. Matrix as a modulator of hepatic fibrogenesis. Sem Liver Dis 2001; 21: 351-372.

  30. Friedman SL. Liver fibrosis – from bench to bedside. J Hepatol 2003; 38: s38-53.

  31. Kinnman N, Housset C. Peribiliary myofibroblasts in biliary type liver fibrosis. Front Biosci 2002; 7: d496-503.

  32. Issa R, Williams E, Trim N, Kendall T, Arthur MJ, Reichen J, Benyon RC, Iredale JP. Apoptosis of hepatic stellate cells: involvement in resolution of biliary fibrosis and regulation by soluble growth factors. Gut 2001; 48: 548-557.

  33. Bueno MR, Daneri A, Armendariz-Borunda J. Cholestasis-induced fibrosis is reduced by interferon alpha-2a and is associated with elevated liver metalloprotease activity. J Hepatol 2000; 33: 915-925.

  34. Aneja R, Upadhyaya G, Prakash S, Dass SK, Chandra R. Ameliorating effect of phytoestrogens on CCl4-induced oxidative stress in the livers of male Wistar rats. Artif Cells Blood Substit Immobil Biotechnol 2005; 33: 201-213.

  35. Griffin DW. Mechanism of action, metabolism and toxicity of buthionine and its higher homologies, potent inhibitors of glutathione synthesis. J Biol Chem 1982; 257: 13704-13712.

  36. Seelig GF, Meister A. Glutathione biosynthesis gamma glutamylcysteine synthetase from rat kidney. Methods Enzymol 1985; 113: 379-390.

  37. Liu XJ, Yang L, Mao YQ, Wang Q, Huang MH, Wang YP, Wu HB. Effects of the tyrosine protein kinase inhibitor genistein on the proliferation, activation of cultured rat hepatic stellate cells. World J Gastroenterol 2002; 8: 739-745.

  38. Chodon D, Banu SM, Padmavathi R, Sakthisekaran D. Inhibition of cell proliferation and induction of apoptosis by genistein in experimental hepatocellular carcinoma. Mol Cell Biochem 2006; 28.

  39. Liu X, Huang M, Cheng N, Xiao W, Wang Y. Effects of genistein on the fenestrate, proliferation and nitric oxide synthesis of liver sinusoidal endothelial cells from carbon tetrachloride-induced experimental hepatic fibrosis rats. Zhonghua Gan Zang Bing Za Zhi 2002; 10: 200-203.

  40. Senties-Gomez MD, Galvez-Gastelum FJ, Meza-Garcia E, Armendariz-Borunda J. Hepatic fibrosis: role of matrix metalloproteases and TGF-beta. Gac Med Mex. 2005; 141: 315-322.

  41. Bedossa P, Paradis V. Regression of hepatic fibrosis physiopathological aspects and clinical reality. Press Med 2003; 32: 704-710.

  42. Fajardo I, Diez E, Rodriguez-Nieto S, Rodriguez-Caso C, Quesada AR, Sanchez-Jimenez F, Medina MA. Effects of genistein and 2-methoxyestradiol on matrix metalloproteinases and their inhibitors secreted by Ehrlich ascites tumor cells. Anticancer Res 2000; 20: 1691-1694.

  43. Garcia de Veas R, Schweigerer L, Medina MA. Modulation of the proteolytic balance plasminogen activator/plasminogen activator inhibitor by enhanced N-myc oncogene expression or application of genistein. Eur J Cancer 1998; 34: 1736-1740.

  44. Santibanez JF, Navarro A, Martinez J. Genistein inhibits proliferation and in vitro invasive potential of human prostatic cancer cell lines. Anticancer Res 1997; 17: 1199-1204.




2020     |     www.medigraphic.com