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Interactions between mefloquine and the anti-fibrotic drug silymarin on Schistosoma mansoni infections in mice

Published online by Cambridge University Press:  29 January 2016

Reem O.A. Kamel
Reem O.A. Kamel*
Affiliation:
Department of Zoology, Faculty of Women for Arts, Science and Education, Ain Shams University, Asmaa Fahmy St, Heliopolis, Cairo11757, Egypt
*
*E-mail: reemosama12@yahoo.com
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Abstract

The present study tests the anti-inflammatory and anti-fibrotic effects of silymarin alone or combined with mefloquine on acute schistosomiasis by evaluating parasitological, histopathological, biochemical and immunological parameters. Male CDI Swiss mice were divided into seven groups, which included healthy controls, mice infected with Schistosoma mansoni or treated with silymarin (140 mg/kg body weight) or mefloquine (400 mg/kg body weight), or mice treated with a combination of both drugs and uninfected mice simply treated with mefloquine or silymarin alone. All mouse groups were sacrificed 8 weeks post-infection (pi) and/or post-treatment. Those infected mice treated with both silymarin and mefloquine showed a significant decrease (P <  0.001) in worm burden, immunoglobulins (IgG and IgM), liver function enzymes and granuloma diameter, with complete eradication of immature and mature eggs. In conclusion, treatment with silymarin combined with mefloquine in murine schistosomiasis was able to reduce granulomatous reactions and hepatic fibrosis. Hence, this combination is a new strategy to be studied as an efficient tool in the treatment of schistosomal liver fibrosis.

Type
Research Papers
Information
Journal of Helminthology , Volume 90 , Issue 6 , November 2016 , pp. 760 - 765
Copyright
Copyright © Cambridge University Press 2016 

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References

Abdel-Hady, M.H., Abaza, B.E., Fathy, G.M., Badawey, M.S., Nada, S.M., El-Shafei, M.A. & Abdel-Aziz, H.R. (2013) Impact of treatment with praziquantel supplemented by silymarin on Schistosoma mansoni-induced fibrosis in mice. The Parasitologists United Journal 6, 77–88.Google Scholar
Andrade, Z.A. (2008) Schistosomiasis and hepatic fibrosis regression. Acta Tropica 108, 79–82.Google Scholar
Bancroft, J.D. & Stevens, A. (1990) Theory and practice of histological techniques. 3rd edn. Edinburgh, Churchill Livingstone.Google Scholar
Burke, M.L., McManus, D.P., Ramm, G.A., Duke, M., Li, Y., Jones, M.K. & Gobert, G.N. (2010) Temporal expression of chemokines dictates the hepatic inflammatory infiltrate in a murine model of schistosomiasis. PLoS Neglected Tropical Diseases 4, e598.Google Scholar
Cheever, A.W. & Anderson, L.A. (1971) Rate of destruction of Schistosoma mansoni eggs in the tissues of mice. American Journal of Tropical Medicine and Hygiene 20, 62–68.Google Scholar
Doenhoff, M.J., Wheeler, J.G., Tricker, K., Hamilton, J.V., Sturrock, R.F., Butterworth, A.E., Ouma, J.H., Mbugua, G.G., Kariuki, C. & Koech, D. (2003) The detection of antibodies against Schistosoma mansoni soluble egg antigens (SEA) and CEF6 in ELISA, before and after chemotherapy. Annals of Tropical Medicine and Parasitology 97, 697–709.Google Scholar
Doenhoff, M.J., Cioli, D. & Utzinger, J. (2008) Praziquantel: mechanisms of action, resistance and new derivatives for schistosomiasis. Current Opinion in Infectious Diseases 21, 659–667.CrossRefGoogle ScholarPubMed
Duvall, R.H. & DeWitt, W.B. (1967) An improved perfusion technique for recovering adult schistosomes from laboratory animals. American Journal of Tropical Medicine and Hygiene 16, 483–486.CrossRefGoogle ScholarPubMed
El-Lakkany, N.M., Hammam, O.A., El-Maadawy, W.H., Badawy, A.A., Ain-Shoka, A.A. & Ebeid, F.A. (2012) Anti-inflammatory/anti-fibrotic effects of the hepatoprotective silymarin and the schistosomicide praziquantel against Schistosoma mansoni-induced liver fibrosis. Parasites & Vectors 5, 1–14.Google Scholar
Engvall, E. & Perlmann, P. (1971) Enzyme linked immunosorbent assay (ELISA) quantitative assay of immunoglobulin G. Immunochemistry 8, 871–874.Google Scholar
Fahmy, S.R., Rabia, I. & Mansour, E.M. (2014) The potential role of mefloquine against Schistosoma mansoni infection by prohibition of hepatic oxidative stress in mice. Journal of Basic and Applied Zoology 67, 40–47.CrossRefGoogle Scholar
Fakahany, A.F., Younis, M.S., El Hamshary, A.M.S., Fouad, M.A.H., Hassan, M.A.E. & Ali, H.S.M. (2014) Effect of mefloquine on worm burden and tegumental changes in experimental Schistosoma mansoni infection. Journal of Microscopy and Ultrastructure 2, 7–11.Google Scholar
Gryseels, B. (2012) Schistosomiasis. Infectious Disease Clinics of North America 26, 383–397.Google Scholar
Ingram, K., Ellis, W. & Keiser, J. (2012) Antischistosomal activities of mefloquine-related arylmethanols. Antimicrobial Agents and Chemotherapy 56, 3207–3215.Google Scholar
Jahan, S., Khan, M., Imran, S. & Sair, M. (2015) The hepatoprotective role of silymarin in isoniazid induced liver damage of rabbits. Journal of the Pakistan Medical Association 65, 620–622.Google Scholar
Jeong, D.H., Lee, G.P., Jeong, W.I., Do, S.H., Yang, H.J., Yuan, D.W., Park, H.Y., Kim, K.J. & Jeong, K.S. (2005) Alterations of mast cells and TGF-β1 on the silymarin treatment for CCl4 induced hepatic fibrosis. World Journal of Gastroenterology 11, 1141–1148.Google Scholar
Kadry, S.M., Mohamed, A.M., Farrag, E.M. & Fayed, D.B. (2013) Influence of some micronutrients and Citharexylum quadrangular extract against liver fibrosis in Schistosoma mansoni infected mice. African Journal of Pharmacy and Pharmacology 7, 2628–2638.Google Scholar
Keiser, J., Silue, K.D., Adiossan, L.K., N'Guessan, N.A., Monsan, N., Utzinger, J. & N'Goran, E.K. (2014) Praziquantel, mefloquine–praziquantel, and mefloquine–artesunate–praziquantel against Schistosoma haematobium: a randomized, exploratory, open-label trial. PLoS Neglected Tropical Diseases 8, e2975.Google Scholar
Kind, P.R.H. & King, E.J. (1954) Determination of alkaline phosphatase activity in serum. Journal Clinical Pathology 7, 322.Google Scholar
Mahmoud, A.A.F. & Warren, K.S. (1974) Anti-inflammatory effect of tartar emetric and nirigdazole: suppression of schistosoma egg granuloma. Journal of Immunology 112, 222–228.Google Scholar
Mata-Santos, H.A., Lino, F., Rocha, C.C., Paiva, C.N., Castelo Branco, M.T. & Pyrrho, A.S. (2010) Silymarin treatment reduces granuloma and hepatic fibrosis in experimental schistosomiasis. Parasitology Research 107, 1429–1434.Google Scholar
Mata-Santos, H.A., Dutra, F.F., Rocha, C.C., Lino, F.G., Xavier, F.R., Chinalia, L.A., Hossy, B.H., Castelo-Branco, M.T.L., Teodoro, A.J., Paiva, C.N. & Pyrrho, A.S. (2014) Silymarin reduces profibrogenic cytokines and reverses hepatic fibrosis in chronic murine schistosomiasis. Antimicrobial Agents and Chemotherapy 58, 2076–2083.Google Scholar
Melek, S.T., El-Sharkawy, M.R. & Khaery, N.M. (2011) Neopterin as a biomarker in liver fibrosis of Schistosoma mansoni . Medical Journal of Cairo University 79, 199–209.Google Scholar
Paiva, C.N. & Pyrrho, A.S. (2014) Silymarin reduces profibrogenic cytokines and reverses hepatic fibrosis in chronic murine schistosomiasis. Antimicrobial Agents and Chemotherapy 58, 2076–2083.Google Scholar
Pellegrino, J., Oliveira, C.A., Faria, J. & Cunha, A. (1962) New approach to the screening of drugs in experimental schistosomiasis mansoni in mice. American Journal of Tropical Medicine and Hygiene 11, 201–215.Google Scholar
Peters, P.A. & Warren, K.S.A. (1969) A rapid method of infecting mice and other laboratory animals with Schistosoma mansoni: subcutaneous injection. Journal of Parasitology 55, 558.Google Scholar
Reitman, S. & Frankel, S.A. (1957) A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. American Journal of Clinical Pathology 28, 56–63.Google Scholar
Setty, S.R., Quereshi, A.A., Viswanath Swamy, A.H., Patil, T., Prakash, T., Prabhu, K. & Gouda, A.V. (2007) Hepatoprotective activity of Calotropis procera flowers against paracetamol-induced hepatic injury in rats. Fitoterapia 78, 451–454.Google Scholar
Song, Z., Deaciuc, I., Song, M., Lee, D.Y., Liu, Y., Ji, X. & McClain, C. (2006) Silymarin protects against acute ethanol-induced hepatotoxicity in mice. Alcoholism, Clinical and Experimental Research 30, 407–413.Google Scholar
Szasz, G. (1974) New substrates for measuring gamma glutamyl transpeptidase activity. Zeitschrift für Klinische Chemie und Klinische Biochemie 12, 228.Google ScholarPubMed
Tawfeek, G.M., Alafifi, A.M. & Azmy, M.F. (2003) Immunological indicators of morbidity in human schistosomiasis mansoni: role of vascular endothelial growth factor and anti-soluble egg antigen IgG4 in disease progression. Journal of the Egyptian Society of Parasitology 33, 597–614.Google Scholar
Tendler, M., Pinto, R.M., Oliveira, L.A., Gebara, G. & Katz, N. (1986) Schistosoma mansoni vaccination with adult worm antigens. International Journal of Parasitology 16, 347–352.Google Scholar
Utzinger, J., Raso, G., Brooker, S., De Savigny, D., Tanner, M., Ornbjerg, N., Singer, B.H. & N'goran, E.K. (2009) Schistosomiasis and neglected tropical diseases: towards integrated and sustainable control and a word of caution. Parasitology 136, 1859–1874.Google Scholar
WHO. (2011) Schistosomiasis: number of people treated in 2009. The Weekly Epidemiological Record 86, 73–80.Google Scholar
Xiao, S.H., Mei, J.Y. & Jiao, P.Y. (2011) Effect of mefloquine administered orally at single, multiple, or combined with artemether, artesunate or praziquantel in treatment of mice infected with Schistosoma japonicum . Parasitology Research 108, 399–406.Google Scholar