Parasitology Research

, Volume 111, Issue 2, pp 577–586 | Cite as

Therapeutic effect of alpha lipoic acid combined with praziquantel on liver fibrosis induced by Schistosoma mansoni challenged mice

  • Ekhlas H. Abdel-Hafeez
  • Azza K. Ahmad
  • Ahlam M. Abdulla
  • Soha Aabdel-Wahab
  • Fadia A. Mosalem
Original Paper

Abstract

Schistosomiasis is an endemic disease in 74 countries causing more than 250,000 deaths every year. Accordingly, the development of an effective drug for eradication of schistosomiasis is an open research field. The current chemotherapy for control is praziquantel (PZQ). However, PZQ does not improve liver fibrosis. Therefore, the aim of this study is to evaluate the combined effect of alpha lipoic acid (ALA) with PZQ on the liver fibrosis induced by Schistosoma mansoni challenged mice. Evaluation was based on the worm burden count, ova load, granuloma size, and histopathology of the liver. Reduced glutathione (GSH) was measured in the tissue as a biomarker for impaired antioxidant function. Malondialdehyde (MDA) was also measured in the tissue as a biomarker for oxidative stress. The serum level of matrix metalloproteinase 1 was measured as a biomarker for fibrotic status of the liver. Liver function enzymes such as ALT, AST, and GGT were also measured. Four groups of ten mice each were used in this study. The first group was infected with 50 ± 10 S. mansoni cercariae. The second group was also infected and was treated with PZQ 9 weeks post-infection (PI). The third group was treated with PZQ and ALA 9 weeks PI. The fourth group was used a healthy control. The present study revealed remarkable improvement in all parameters measured (parasitological and biochemical) as well as significant improvement of hepatic pathology in the third group which was treated with PZQ and ALA. The treatment of mice with PZQ and ALA results in reduction in the worm burden, egg count, and granuloma size. Furthermore, this combined treatment increased the tissue level of the antioxidant (GSH) and decreased the tissue level of MDA in this group.

Keywords

Liver Fibrosis Schistosomiasis Praziquantel Infected Group Worm Burden 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

The authors would like to thank Prof. Nabil S. Gabr, Head of the Department of Parasitology, Faculty of Medicine, Minia University, Egypt, for his continuous advice in technical procedures. Thanks are extended to Prof. Nawras M. Mowafy, Professor of Parasitology, Faculty of Medicine, Minia University for her guiding us through the technical procedures. The authors would also like to thank Prof. Refaat M. A. Khalifa, Professor of Parasitology, Faculty of Medicine, Assuit University for his continuous advice.

References

  1. Abdallahi OM, Hanna S, De Reggi M, Gharib B (1999) Visualization of oxygen radical production in mouse liver in response to infection with Schistosoma mansoni. Liver 19:495–500PubMedCrossRefGoogle Scholar
  2. Bataller R, Brenner DA (2005) Liver fibrosis. J Clin Invest 115:209–18PubMedGoogle Scholar
  3. Biempica L, Takahashi S, Biempica S, Kobayashi M (1983) Immunohistochemical localization of collagenase in hepatic murine schistosomiasis. J Histochem Cytochem 31:488–494PubMedCrossRefGoogle Scholar
  4. Biewenga GP, Haenen GR, Bast A (1997) The pharmacology of the antioxidant lipoic acid. Gen Pharmacol 29:315–31PubMedCrossRefGoogle Scholar
  5. Brown KE, Poulos JE, Li L, Soweid AM, Ramm GA, O’Neill R, Britton RS, Bacon BR (1997) Effect of vitamin E supplementation on hepatic fibrogenesis in chronic dietary iron overload. Am J Physiol 272:G116–G123PubMedGoogle Scholar
  6. Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–10PubMedCrossRefGoogle Scholar
  7. Castillo T, Koop DR, Kamimura S, Triadafilopoulos G, Tsukamoto H (1992) Role of cytochrome P-450 2E1 in ethanol-, carbon tetrachloride- and iron-dependent microsomal lipid peroxidation. Hepatology 16:992–996PubMedCrossRefGoogle Scholar
  8. Cheever AW (1968) Condition affecting the accuracy of potassium hydroxide digestion technique for counting Schistosoma mansoni eggs in tissue. Bull World Health 39:328–31Google Scholar
  9. Cioli D (2000) Praziquantel: is there real resistance and are there alternatives? Curr Opin Infect Dis 13:659–663PubMedCrossRefGoogle Scholar
  10. Dabski H, Brzeski Z (1970) Treatment of chronic diseases of the liver parenchyma with thioctic acid. Pol Tyg Lek 25:899–901PubMedGoogle Scholar
  11. Dunn MA, Kamel R, Kamel IA, Biempica L, Kholy AE, Hait PK, Rojkind M, Warren KS, Mahmoud AA (1979) Liver collagen synthesis in schistosomiasis mansoni. Gastroenterology 76:978–82PubMedGoogle Scholar
  12. Dünschede F, Erbes K, Kircher A, Westermann S, Seifert J, Schad A, Oliver K, Kiemer AK, Theodor J (2006) Reduction of ischemia reperfusion injury after liver resection and hepatic inflow occlusion by alpha-lipoic acid in humans. World J Gastroenterol 12:6812–7PubMedGoogle Scholar
  13. Duvall R, DeWitt W (1967) An improved perfusion technique for recovering adult schistosomes from laboratory animals. Am J Trop Med Hyg 16:483–6PubMedGoogle Scholar
  14. Seif el-Din SH, Ebeid FA, Badawy AA, Ezzat AR (2006) Protective effects of β-carotene, N-acetyl-cysteine with and without praziquantel treatment in Schistosoma mansoni-infected mice. Egyptian J Schistosomiasis Infect Endemic Dis 28:67–90Google Scholar
  15. Seif el-Din SH, Al-Hroob AM B, Ebeid FA (2011) Schistosoma mansoni: N-acetylcysteine downregulates oxidative stress and enhances the antischistosomal activity of artemether in mice. Exp Parasitol 128:230–235PubMedCrossRefGoogle Scholar
  16. El-Shenawy NS, Soliman MFM (2003) Evaluation of the protective effect of two antioxidative agents in mice experimentally induced with Schistosoma mansoni: biochemical and parasitological aspects. J Egypt Ger Zool 40(A):201–216Google Scholar
  17. Emonard H, Grimaud JA (1989) Active and latent collagenase activity during reversal of hepatic fibrosis in murine schistosomiasis. Hepatology 10:77–83PubMedCrossRefGoogle Scholar
  18. Ezzat AR, Seif el-Din SH, Ebeid FA (2001) Effect of praziquantel treatment on the activities of some liver microsomal enzymes in mice infected with S. mansoni. Arzneimittelforschung 51:325–331PubMedGoogle Scholar
  19. Franco R, Schoneveld OJ, Pappa A, Panayiotidis MI (2007) The central role of glutathione in the pathophysiology of human diseases. Arch Physiol Biochem 113:234–58PubMedCrossRefGoogle Scholar
  20. Geesin JC, Hendricks LJ, Falkenstein PA, Gordon JS, Berg RA (1991) Regulation of collagen synthesis by ascorbic acid: characterization of the role of ascorbate-stimulated lipid peroxidation. Arch Biochem Biophys 290:127–132PubMedCrossRefGoogle Scholar
  21. Gharib B, Abdallahi OM, Dessein H, De Reggi M (1999) Development of eosinophil peroxidase activity and concomitant alteration of the antioxidant defenses in the liver of mice infected with Schistosoma mansoni. J Hepatol 30:594–602PubMedCrossRefGoogle Scholar
  22. Hammad H, Sherif S, Ebeid F (2000) Effect of praziquantel on some biochemical aspects in experimental schistosomiasis. Recent Res Dev Biotechnol Bioeng 3:107–118Google Scholar
  23. Harvie M, Jordan TW, La Flamme AC (2007) Differential liver protein expression during schistosomiasis infection and immunity. Infect Immun 75: 736-744Google Scholar
  24. Hirsch C, Zouain CS, Alves JB, Goes AM (1997) Induction of protective immunity and modulation of granulomatous hypersensitivity in mice using PIII, an anionic fraction of Schistosoma mansoni adult worm. Parasitology 115:21–2PubMedCrossRefGoogle Scholar
  25. Horáková O, Kostír J, Horák F (1967) The hepatotropic effect of alpha-lipoic acid. Cesk Farm 16:129–33PubMedGoogle Scholar
  26. Hsu SM, Raine L, Protein A (1981) Avidin and biotin in immunohistochemistry. J Histochem Cytochem 29:1349–53PubMedCrossRefGoogle Scholar
  27. Iasinovskii MA, Terletskaia TM, Bondarchuk AF (1969) Use of lipoic acid in complex therapy of patients with liver diseases. Vrach Delo 5:9–12PubMedGoogle Scholar
  28. Ito K, Kajikawa S, Nii A, Doi K (2005) Nitrofurazone-induced gene expressions in rat hepatocytes and their modification by N-acetylcysteine. Exp Toxicol Pathol 56:333–339PubMedCrossRefGoogle Scholar
  29. Ivkov VG (1969) Lipoic (thioctic) acid and its significance in hepatology. Sov Med 32(10):122–8PubMedGoogle Scholar
  30. Junqueira L, Montes G, Toledo O, Joarzeino P (1986) Morphological, histochemical and biochemical observations on the connective tissue matrix of in situ and isolated hepatic granulomas in experimental murine schistosomiasis. Ann Trop Med Parasitol 80:27–41PubMedGoogle Scholar
  31. Lescano SZ, Chieffe PP, Canhassi RR, Boulos M, Amato Neto V (2004) Antischistosomal activity of artemether in experimental schistosomiasis mansoni. Rev Saude Publica 38:71–75PubMedCrossRefGoogle Scholar
  32. Liang SM, Liang CM, Hargrove ME, Ting CC (1991) Regulation by glutathione of the effect of lymphokines on differentiation of primary activated lymphocytes. Influence of glutathione on cytotoxic activity of CD3-AK. J Immunol 146:1909–1913PubMedGoogle Scholar
  33. Lieber CS (1994) Alcohol and the liver update. Gastroenterology 106:1085–1105PubMedGoogle Scholar
  34. Mahmoud MR, EI-Abhar HS, Saleh S (2002a) The effect of Nigella sativa oil against liver damage induced by Schistosoma mansoni infection in mice. J Ethnopharmacol 79:1–11PubMedCrossRefGoogle Scholar
  35. Mahmoud MR, Zoheiry MMK, Nosseir MF (2002b) Effect of combined chemotherapy and anti-inflammatory drugs on murine schistosomiasis. Arzneimittelforschung 52:294–301PubMedGoogle Scholar
  36. Melhem MF, Craven PA, DeRubertis FR (2001) Effects of dietary supplementation of α-lipoic acid on early glomerular injury in diabetes. J Am Soc Nephrol 12:124–133PubMedGoogle Scholar
  37. Möller E, Brinkmann W, Weber O, Wildhirt E (1967) Treatment of chronic liver diseases with thioctic acid. Med Klin 62:380–4PubMedGoogle Scholar
  38. Morsy GH (2009) Parasitological and histo-pathological studies on schistosomiasis mansoni infected mice and treated with praziquantel and/or oltipraz. J Egypt Soc Parasitol 39:687–701PubMedGoogle Scholar
  39. Murawaki Y, Ikuta Y, Idobe Y, Kawasaki H (1999) Serum matrix metalloproteinase-1 in patients with chronic viral hepatitis. J Gastroenterol Hepatol 14:138–45PubMedCrossRefGoogle Scholar
  40. Nare B, Smith JM, Prichard RK (1990) Schistosoma mansoni: levels of antioxidants and resistance to oxidants increase during development. Exp Parasitol 70:389–397PubMedCrossRefGoogle Scholar
  41. Nordmann R, Ribiere C, Rouach H (1992) Implication of free radical mechanisms in ethanol-induced cellular injury. Free Radic Biol Med 12:219–240PubMedCrossRefGoogle Scholar
  42. Oliver L, Stirewalt MA (1952) An efficient method for the exposure of mice to cercariae of S. mansoni. J Parasitol 39:19–23CrossRefGoogle Scholar
  43. Pascal M, Abdallahi OM, Elwali NE, Mergani A, Qurashi MA, Magzoub M, de Reggi M, Gharib B (2000) Hyaluronate levels and markers of oxidative stress in the serum of Sudanese subjects at risk of infection with Schistosoma mansoni. Trans R Soc Trop Med Hyg 94:66–70PubMedCrossRefGoogle Scholar
  44. Pellegrino J, Oliveria CA, Faria J, Cunha A (1962) New approach to the screening of the drugs in experimental Schistosoma mansoni in mice. Am J Trop Med Hyg 1:201–15Google Scholar
  45. Pocernich CB, La Fontaine M, Butterfield DA (2000) In-vivo glutathione elevation protects against hydroxyl free radical-induced protein oxidation in rat brain. Neurochem Int 36:185–191PubMedCrossRefGoogle Scholar
  46. Rehermann B, Nascimbeni M (2005) Immunology of hepatitis B virus and hepatitis-C virus infection. Nature Rev Immunol 5:215–229CrossRefGoogle Scholar
  47. Romanov VS (1971) Use of lipoic acid and its amide in chronic liver diseases. Sov Med 34:43–5PubMedGoogle Scholar
  48. Smithers RS, Terry RJ (1965) The infection of laboratory hosts with cercariae of S. mansoni and the recovery of worm. Parasitology 55:695–700PubMedGoogle Scholar
  49. Takahashi S, Dunn MA, Seifter S (1980) Liver collagenase in murine schistosomiasis. Gastroenterology 78:1425–1431PubMedGoogle Scholar
  50. Tendler M, Pinto RM, Lima AO, Gebara G, Katz N (1968) Schistosoma mansoni: vaccination with adult worm antigen. Int J Parasitol 16:347–352CrossRefGoogle Scholar
  51. Xiong LJ, Zhu JF, Luo DD, Zen LL, Cai SQ (2003) Effects of pentoxifylline on the hepatic content of TGF-β1 and collagen in schistosomiasis japonica mice with liver fibrosis. World J Gastroent 9:152–154Google Scholar
  52. Zhang BB, Cai WM, Weng HL, Hu ZR, Lu J, Zheng M, Liu RH (2003) Diagnostic value of platelet derived growth factor-BB, transforming growth factor-beta matrix metalloproteinase-1 and tissue inhibitor of matrix metalloproteinase-1 in serum and peripheral blood mononuclear cells for hepatic fibrosis. World J Gastroenterol 9:2490–6PubMedGoogle Scholar
  53. Zou WL, Yang Z, Zang YJ, Li DJ, Liang ZP, Shen ZY (2007) Inhibitory effects of prostaglandin E1 on activation of hepatic stellate cells in rabbits with schistosomiasis. Hepatobiliary Pancreatol Distrib Int 6:176–181Google Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Ekhlas H. Abdel-Hafeez
    • 1
  • Azza K. Ahmad
    • 1
  • Ahlam M. Abdulla
    • 2
  • Soha Aabdel-Wahab
    • 3
  • Fadia A. Mosalem
    • 4
  1. 1.Department of Parasitology, Faculty of MedicineMinia UniversityMiniaEgypt
  2. 2.Department of Biochemistry, Faculty of MedicineMinia UniversityMiniaEgypt
  3. 3.Department of Histology, Faculty of MedicineMinia UniversityMiniaEgypt
  4. 4.Department of Public Health and Preventive Medicine, Faculty of MedicineMinia UniversityMiniaEgypt

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