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Synergistic Effects of Jerusalem Artichoke in Combination with Pegylated Interferon Alfa-2a and Ribavirin Against Hepatic Fibrosis in Rats

  • Abdel-Hamid, Nabil Mohie (Biochemistry Department, Faculty of Pharmacy, Kafr-El-Sheikh University) ;
  • Wahid, Ahmed (Biochemistry Department, Faculty of Pharmacy, Minia University) ;
  • Nazmy, Maiiada Hassan (Biochemistry Department, Faculty of Pharmacy, Minia University) ;
  • Eisa, Marwa Abdel-Moniem (Biochemistry Department, Faculty of Pharmacy, Minia University)
  • Published : 2016.06.01

Abstract

Background: Complementary and alternative medicine has been highly appreciated as a supportive regimen for classical treatment strategies. Here we offer a nutrition-based adjuvant therapy for liver fibrosis, a major risk factor for cirrhosis and hepatocellular carcinoma. Aim of the study: To evaluate the possible hepatoprotective effects of Jerusalem artichoke tubers (JAT) in combination with interferon and ribavirin. Materials and Methods: Twelve groups of rats were administered JAT, interferon and ribavirin either separately or in combination from day one of $CCL_4$ administration until the end of the study. Animals were killed after 8 weeks of $CCL_4$-induced hepatotoxicity. Results: Hepatocytes from rats treated with triple combination of interferon, ribavirin, and JAT showed more less normal architecture compared to $CCL_4$-treated rats. We also detected significantly higher hepatic protein expression levels of p53, BAX and transforming growth factor-${\beta}$ (TGF-${\beta}$) in the $CCL_4$-intoxicated group compared to normal controls, as evidenced by immunohistochemical staining and western blotting analyses. Addition of JAT as a supportive regimen improved response to ribavirin and interferon and effectively participated in retaining normal histopathological and biochemical criteria and significantly lowered protein expression of p53, BAX, and TGF-${\beta}$. Conclusions: We suggest that addition of JAT as a supportive r egimen to interferon and ribavirin effectively potentiates their anti-fibrotic effects.

Keywords

Jerusalem artichoke tubers;rat liver model;fibrosis;p53;BAX;TGF-${\beta}$

References

  1. Abdel Salam OM, Sleem AA, Omara EA, et al (2007). Effect of ribavirin alone or combined with silymarin on carbon tetrachloride induced hepatic damage in rats. Drug Target Insights, 2, 19-27.
  2. Abdel-Hamid NM, Nazmy MH, Mahmoud AW, et al (2011). A survey on herbal management of hepatocellular carcinoma. World J Hepatol, 3, 175-83. https://doi.org/10.4254/wjh.v3.i7.175
  3. Abdel-Hamid NM, Nazmy MH, Wahid A, et al (2015). Jerusalem artichoke attenuates experimental hepatic fibrosis via modulation of apoptotic signaling and fibrogenic activity. Biochemistry Biotechnol Res, 3, 43-50.
  4. Aithal GP, Watkins PB, Andrade RJ, et al (2011). Case definition and phenotype standardization in drug-induced liver injury. Clin Pharmacol Ther, 89, 806-15. https://doi.org/10.1038/clpt.2011.58
  5. Akyol G, Dursun A, Poyraz A, et al (1999). P53 and proliferating cell nuclear antigen (PCNA) expression in non-tumoral liver diseases. Pathol Int, 49, 214-21. https://doi.org/10.1046/j.1440-1827.1999.00849.x
  6. Althnaian T, Albokhadaim I, El-Bahr SM (2013). Biochemical and histopathological study in rats intoxicated with carbontetrachloride and treated with camel milk. Springerplus, 2, 57. https://doi.org/10.1186/2193-1801-2-57
  7. Arici OF, Cetin N (2011). Protective role of ghrelin against carbon tetrachloride (CCl(4))-induced coagulation disturbances in rats. Regul Pept, 166, 139-42. https://doi.org/10.1016/j.regpep.2010.10.009
  8. Aslan M, Orhan N, Orhan DD, et al (2010). Hypoglycemic activity and antioxidant potential of some medicinal plants traditionally used in Turkey for diabetes. J Ethnopharmacol, 128, 384-9. https://doi.org/10.1016/j.jep.2010.01.040
  9. Attallah AM, Shiha GE, Ismail H, et al (2009). Expression of p53 protein in liver and sera of patients with liver fibrosis, liver cirrhosis or hepatocellular carcinoma associated with chronic HCV infection. Clin Biochem, 42, 455-61. https://doi.org/10.1016/j.clinbiochem.2008.11.004
  10. Baldo V, Baldovin T, Trivello R, et al (2008). Epidemiology of HCV infection. Curr Pharm Des, 14, 1646-54. https://doi.org/10.2174/138161208784746770
  11. Bataller R, Brenner DA (2005). Liver fibrosis. J Clin Invest, 115, 209-18. https://doi.org/10.1172/JCI24282
  12. Blight KJ, McKeating JA, Marcotrigiano J, et al (2003). Efficient replication of hepatitis C virus genotype 1a RNAs in cell culture. J Virol, 77, 3181-90. https://doi.org/10.1128/JVI.77.5.3181-3190.2003
  13. Boigk G, Stroedter L, Herbst H, et al (1997). Silymarin retards collagen accumulation in early and advanced biliary fibrosis secondary to complete bile duct obliteration in rats. Hepatol, 26, 643-9. https://doi.org/10.1002/hep.510260316
  14. Brattin WJ, Glende EA, Jr., Recknagel RO (1985). Pathological mechanisms in carbon tetrachloride hepatotoxicity. J Free Radic Biol Med, 1, 27-38. https://doi.org/10.1016/0748-5514(85)90026-1
  15. Castilla A, Prieto J, Fausto N (1991). Transforming growth factors beta 1 and alpha in chronic liver disease. Effects of interferon alfa therapy. N Engl J Med, 324, 933-40. https://doi.org/10.1056/NEJM199104043241401
  16. Chang WC, Jia H, Aw W, et al (2014). Beneficial effects of soluble dietary Jerusalem artichoke (Helianthus tuberosus) in the prevention of the onset of type 2 diabetes and nonalcoholic fatty liver disease in high-fructose diet-fed rats. Br J Nutr, 112, 709-17. https://doi.org/10.1017/S0007114514001421
  17. Chang XM, Chang Y, Jia A (2005). Effects of interferon-alpha on expression of hepatic stellate cell and transforming growth factor-beta1 and alpha-smooth muscle actin in rats with hepatic fibrosis. World J Gastroenterol, 11, 2634-6. https://doi.org/10.3748/wjg.v11.i17.2634
  18. CR T (1994). The current role of immunohistochemistry in diagnostic pathology. Adv Pathol Lab Med, 7.
  19. Domitrovic R, Jakovac H, Tomac J, et al (2009). Liver fibrosis in mice induced by carbon tetrachloride and its reversion by luteolin. Toxicol Appl Pharmacol, 241, 311-21. https://doi.org/10.1016/j.taap.2009.09.001
  20. EA Z (2009). Physiological response to diets fortified with Jerusalem artichoke tubers (Helianthus tuberosus L.) powder by diabetic rats. American-Eurasian J Agric Environ Sci, 5, 682-8.
  21. Fujii H, Nishimura T, Umemura A, et al (2015). Comparison of peg-interferon, ribavirin plus telaprevir vs simeprevir by propensity score matching. World J Hepatol, 7, 2841-8. https://doi.org/10.4254/wjh.v7.i28.2841
  22. Gao B, Bataller R (2011). Alcoholic liver disease: pathogenesis and new therapeutic targets. Gastroenterol, 141, 1572-85. https://doi.org/10.1053/j.gastro.2011.09.002
  23. Gebhardt R (2002). Oxidative stress, plant-derived antioxidants and liver fibrosis. Planta Med, 68, 289-96. https://doi.org/10.1055/s-2002-26761
  24. Green DR (2000). Apoptotic pathways: paper wraps stone blunts scissors. Cell, 102, 1-4. https://doi.org/10.1016/S0092-8674(00)00003-9
  25. Guo XL, Liang B, Wang XW, et al (2013). Glycyrrhizic acid attenuates CCl(4)-induced hepatocyte apoptosis in rats via a p53-mediated pathway. World J Gastroenterol, 19, 3781-91. https://doi.org/10.3748/wjg.v19.i24.3781
  26. Helm M, Brule H, Giege R, et al (1999). More mistakes by T7 RNA polymerase at the 5 ' ends of in vitro-transcribed RNAs. RNA, 5, 618-21. https://doi.org/10.1017/S1355838299982328
  27. Hengartner MO (2000). The biochemistry of apoptosis. Nature, 407, 770-6. https://doi.org/10.1038/35037710
  28. Kucukgergin C, Aydin AF, Ozdemirler-Erata G, et al (2010). Effect of artichoke leaf extract on hepatic and cardiac oxidative stress in rats fed on high cholesterol diet. Biol Trace Elem Res, 135, 264-74. https://doi.org/10.1007/s12011-009-8484-9
  29. Lotersztajn S, Julien B, Teixeira-Clerc F, et al (2005). Hepatic fibrosis: molecular mechanisms and drug targets. Annu Rev Pharmacol Toxicol, 45, 605-28. https://doi.org/10.1146/annurev.pharmtox.45.120403.095906
  30. Mayo MJ (2011). Management of autoimmune hepatitis. Curr Opin Gastroenterol, 27, 224-30. https://doi.org/10.1097/MOG.0b013e3283457ce0
  31. McCay PB, Lai EK, Poyer JL, et al (1984). Oxygen- and carboncentered free radical formation during carbon tetrachloride metabolism. Observation of lipid radicals in vivo and in vitro. J Biol Chem, 259, 2135-43.
  32. Mehmetcik G, Ozdemirler G, Kocak-Toker N, et al (2008). Role of carnosine in preventing thioacetamide-induced liver injury in the rat. Peptides, 29, 425-9. https://doi.org/10.1016/j.peptides.2007.11.008
  33. Minano C, Garcia-Tsao G (2010). Clinical pharmacology of portal hypertension. Gastroenterol Clin North Am, 39, 681-95. https://doi.org/10.1016/j.gtc.2010.08.015
  34. Muriel P (1996). Alpha-interferon prevents liver collagen deposition and damage induced by prolonged bile duct obstruction in the rat. J Hepatol, 24, 614-21. https://doi.org/10.1016/S0168-8278(96)80148-6
  35. Nobili V, Carter-Kent C, Feldstein AE (2011). The role of lifestyle changes in the management of chronic liver disease. BMC Med, 9, 70. https://doi.org/10.1186/1741-7015-9-70
  36. Panasiuk A, Dzieciol J, Panasiuk B, et al (2006). Expression of p53, Bax and Bcl-2 proteins in hepatocytes in non-alcoholic fatty liver disease. World J Gastroenterol, 12, 6198-202. https://doi.org/10.3748/wjg.v12.i38.6198
  37. Papakyriakou P, Tzardi M, Valatas V, et al (2002). Apoptosis and apoptosis related proteins in chronic viral liver disease. Apoptosis, 7, 133-41. https://doi.org/10.1023/A:1014472430976
  38. Punzi R, Paradiso A, Fasciano C, et al (2014). Phenols and antioxidant activity in vitro and in vivo of aqueous extracts obtained by ultrasound-assisted extraction from artichoke by-products. Nat Prod Commun, 9, 1315-8.
  39. Ramalho RM, Cortez-Pinto H, Castro RE, et al (2006). Apoptosis and Bcl-2 expression in the livers of patients with steatohepatitis. Eur J Gastroenterol Hepatol, 18, 21-9. https://doi.org/10.1097/00042737-200601000-00005
  40. Reitman S, Frankel S (1957). A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol, 28, 56-63. https://doi.org/10.1093/ajcp/28.1.56
  41. Riley TR, 3rd, Bhatti AM (2001). Preventive strategies in chronic liver disease: part II. Cirrhosis. Am Fam Physician, 64, 1735-40.
  42. Roberfroid MB, Delzenne NM (1998). Dietary fructans. Annu Rev Nutr, 18, 117-43. https://doi.org/10.1146/annurev.nutr.18.1.117
  43. Roberfroid MB, Van Loo JA, Gibson GR (1998). The bifidogenic nature of chicory inulin and its hydrolysis products. J Nutr, 128, 11-9. https://doi.org/10.1093/jn/128.1.11
  44. Roderfeld M, Geier A, Dietrich CG, et al (2006a). Cytokine blockade inhibits hepatic tissue inhibitor of metalloproteinase-1 expression and up-regulates matrix metalloproteinase-9 in toxic liver injury. Liver Int, 26, 579-86. https://doi.org/10.1111/j.1478-3231.2006.01271.x
  45. Roderfeld M, Weiskirchen R, Wagner S, et al (2006b). Inhibition of hepatic fibrogenesis by matrix metalloproteinase-9 mutants in mice. FASEB J, 20, 444-54. https://doi.org/10.1096/fj.05-4828com
  46. Sakaida I, Tsuchiya M, Kawaguchi K, et al (2003). Herbal medicine Inchin-ko-to (TJ-135) prevents liver fibrosis and enzyme-altered lesions in rat liver cirrhosis induced by a choline-deficient L-amino acid-defined diet. J Hepatol, 38, 762-9.
  47. Schafer T, Scheuer C, Roemer K, et al (2003). Inhibition of p53 protects liver tissue against endotoxin-induced apoptotic and necrotic cell death. FASEB J, 17, 660-7. https://doi.org/10.1096/fj.02-0774com
  48. Schuppan D, Afdhal NH (2008). Liver cirrhosis. Lancet, 371, 838-51. https://doi.org/10.1016/S0140-6736(08)60383-9
  49. Schuppan D, Jia JD, Brinkhaus B, et al (1999). Herbal products for liver diseases: a therapeutic challenge for the new millennium. Hepatology, 30, 1099-104.
  50. Serni E, Audino V, Del Carlo S, et al (2013). Determination of water-soluble vitamins in multivitamin dietary supplements and in artichokes by micellar electrokinetic chromatography. Nat Prod Res, 27, 2212-5. https://doi.org/10.1080/14786419.2013.800977
  51. Shahnazari P, Sayehmiri K, Minuchehr Z, et al (2014). The increased level of serum p53 in hepatitis b-associated liver cirrhosis. Iran J Med Sci, 39, 446-51.
  52. Solbrig MV, Schlaberg R, Briese T, et al (2002). Neuroprotection and reduced proliferation of microglia in ribavirin-treated bornavirus-infected rats. Antimicrob Agents Chemother, 46, 2287-91. https://doi.org/10.1128/AAC.46.7.2287-2291.2002
  53. Tasci I, Mas MR, Vural SA, et al (2007). Pegylated interferonalpha plus taurine in treatment of rat liver fibrosis. World J Gastroenterol, 13, 3237-44. https://doi.org/10.3748/wjg.v13.i23.3237
  54. Thursz M, Yee L, Khakoo S (2011). Understanding the host genetics of chronic hepatitis B and C. Semin Liver Dis, 31, 115-27. https://doi.org/10.1055/s-0031-1276642
  55. Towbin H, Staehelin T, Gordon J (1979). Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A, 76, 4350-4. https://doi.org/10.1073/pnas.76.9.4350
  56. Tsamandas AC, Thomopoulos K, Zolota V, et al (2003). Potential role of bcl-2 and bax mRNA and protein expression in chronic hepatitis type B and C: a clinicopathologic study. Mod Pathol, 16, 1273-88. https://doi.org/10.1097/01.MP.0000097367.56816.5E
  57. Tsushima H, Kawata S, Tamura S, et al (1999). Reduced plasma transforming growth factor-beta1 levels in patients with chronic hepatitis C after interferon-alpha therapy: association with regression of hepatic fibrosis. J Hepatol, 30, 1-7.
  58. Veillon P, Fouchard-Hubert I, Larrey D, et al (2015). Does epoetin beta still have a place in peginterferon alpha-2a plus ribavirin treatment strategies for chronic hepatitis c? J Interferon Cytokine Res.
  59. Vogelstein B, Lane D, Levine AJ (2000). Surfing the p53 network. Nature, 408, 307-10. https://doi.org/10.1038/35042675
  60. Vousden KH, Lu X (2002). Live or let die: the cell’s response to p53. Nat Rev Cancer, 2, 594-604. https://doi.org/10.1038/nrc864
  61. Watson D, Rogers JA (1961). A study of six representative methods of plasma bilirubin analysis. J Clin Pathol, 14, 271-8. https://doi.org/10.1136/jcp.14.3.271
  62. Xu XB, Leng XS, Yang X, et al (2004). Obstruction of TGF-beta1 signal transduction can decrease the process of hepatocellular carcinoma in mice induced by CCl4/ethanol. Zhonghua Yi Xue Za Zhi, 84, 1122-5 (in Chinese).
  63. Zawistowski J, Blank G, Murray ED (1986). Polyphenol oxidase activity in Jerusalem artichokes (Helianthus tuberosus L.). Can Institute Food Science Technol J, 19, 210-4. https://doi.org/10.1016/S0315-5463(86)71669-6