Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Acta Parasitologica

4 Issues per year


IMPACT FACTOR 2016: 1.160
5-year IMPACT FACTOR: 1.185

CiteScore 2016: 1.24

SCImago Journal Rank (SJR) 2016: 0.532
Source Normalized Impact per Paper (SNIP) 2016: 0.721

Online
ISSN
1896-1851
See all formats and pricing
More options …
Volume 62, Issue 4

Issues

Anti-angiogenic and anti-lymphangiogenic role of praziquantel and artemether in experimental mansoniasis

Naglaa Fathy Abd El-Aal / Rania Said Hamza / Mona Magdy
Published Online: 2017-10-15 | DOI: https://doi.org/10.1515/ap-2017-0085

Abstract

Angiogenesis is one of the pillars of neoplasia. Lymphangiogenesis in context of granulomas is not yet understood. This study aimed to evaluate the role of praziquantel (PZQ) and artemether (ART) as anti-angiogenic and anti-lymphangiogenic drugs in Schistosoma mansoni induced experimental hepatic model through immunohistochemical and serological studies, this can be used as a potential novel prophylactic approach in hepatic malignancy prevention and possible management. Forty female CD-1 Swiss albino mice were used divided into 4 groups (10 mice each); control healthy, control infected untreated, PZQ-treated and ART-treated. Angiogenic and lymphangiogenic effect of the drugs assessed pathologically through counting of the newly formed capillaries and lymphatics that immunohistochemically expressed by vascular Endothelial Growth Factor (VEGF), CD34 and D2-40 in liver sections using Cell Image Analyzer and serologically by evaluation of serum level of Tumor Necrosis Factor-Alpha (TNF-α). Our results showed significant decrease in serum TNF-α in ART-treated group compared to control infected and PZQ treated groups. ART exhibited significant anti-angiogenic role on granulomas illustrated by remarkable milder intensity and significantly lower expression values of VEGF and CD34 immunostaining compared to PZQ and non-treated groups. Also, ART treated group exhibited negative D2-40 expression in the granulomas in contrast to the other groups, supporting the potent ART‘ anti-lymphangiogenic role that exceeded PZQ. In conclusion, ART showed not only anti-angiogenic effect but also prominent anti-lymphangiogenic effect on hepatic S. mansoni granulomas compared to PZQ. Our study supports the potential use of ART as a potential novel prophylactic approach in hepatic malignancy prevention and possible management.

Keywords: Schistosoma mansoni; anti-angiogenic; anti-lymphangiogenic; VEGF; CD34; D2-40; TNF-α

References

  • Abdel Fattah N.S., Ahmed N.S. 2012. Evidence of intra-hepatic vascular proliferation remodeling early after cure in experimental schistosomiasis mansoni: an immunohistochemical descriptive study. Experimental Parasitology, 130, 58–62. CrossrefWeb of SciencePubMedGoogle Scholar

  • Aggarwal B.B. 2003. Signalling pathways of the TNF superfamily: a double-edged sword. Nature Reviews Immunology, 3, 745–756. CrossrefPubMedGoogle Scholar

  • Andrade Z.A. 2004. Schistosomal hepatopathy. Memórias do Instituto Oswaldo Cruz 99 (Suppl1), 51–57PubMedCrossrefGoogle Scholar

  • Andrade Z.A. 2009. Schistosomiasis and liver fibrosis. Parasite Immunology 31, 656–663. CrossrefPubMedWeb of ScienceGoogle Scholar

  • Andrade Z.A., Santana T.S. 2010. Angiogenesis and schistosomiasis. Memórias do Instituto Oswaldo Cruz Rio de Janeiro, 105, 436–439CrossrefGoogle Scholar

  • Andrade Z.A., Baptista A.P., Santana T.S. 2006. Remodeling of hepatic vascular changes after specific chemotherapy of schistosomal periportal fibrosis. Memórias do Instituto Oswaldo Cruz, 101(Suppl 1), 267–272CrossrefPubMedGoogle Scholar

  • Bancroft S., Stevens A.(Eds) 1982. Theory and practice of histological techniques. 2nd ed. Churchill-Livingston, New YorkGoogle Scholar

  • Carmeliet P., Jain R.K. 2000. Angiogenesis in cancer and other diseases. Nature, 407, 249–257. CrossrefPubMedGoogle Scholar

  • Chen H.H., Zhou H.J., Wu G.D., Lou X. E. 2004. Inhibitory effects of artesunate on angiogenesis and on expressions of vascular endothelial growth factor and VEGF receptor KDR/flk-1. Pharmacology, 71, 1–9. CrossrefPubMedGoogle Scholar

  • Chung C., Iwakiri Y. 2013. The lymphatic vascular system in liver diseases: its role in ascites formation. Clinical and molecular hepatology, 19, 99–104. CrossrefPubMedGoogle Scholar

  • DeLeve L.D. 2013. Liver sinusoidal endothelial cells and liver regeneration. Journal of Clinical Investigation, 123, 1861–1866. CrossrefWeb of ScienceGoogle Scholar

  • Dudek Az., Gupta K., Ramakrishnan S., Mukhopadhyay D. 2010. Tumor angiogenesis. Oncology, 1–2. http://dx.doi.org/10.1155/2010/761671

  • Fedchenko N., Reifenrath J. 2014. Different approaches for interpretation and reporting of immunohistochemistry analysis results in the bone tissue – a review. Diagnostic Pathology, 9, 221. CrossrefWeb of SciencePubMedGoogle Scholar

  • Firestone G.L., Sundar S.N. 2009. Anticancer activities of artemisinin and its bioactive derivatives. Expert Reviews in Molecular Medicine Journal, 11, e32.CrossrefGoogle Scholar

  • Franchitto A., Paolo O., Anastasia R., Guido C., Romina M., Domenico A., Eugenio G. 2013. Expression of vascular endothelial growth factors and their receptors by hepatic progenitor cells in human liver diseases. HepatoBiliary Surgery and Nutrition 2, http://hbsn.amegroups.com/article/view/1170/1847

  • Gligorijević J., Djordjević B., Petrović A., Radirević A., Stojanović S. 2010. Expression of CD34 in cirrhotic liver—reliance to dedifferentiation. World Journal of Vojnosanit Pregl, 67, 459–462CrossrefGoogle Scholar

  • Hammam O., Mahmoud O., Zahran M., Sayed A., Salama R., Hosny K., Farghly A.A. 2013. Liver Disease and Hepatocellular Carcinoma. Gastrointestinal Cancer Research, 6,107–114Google Scholar

  • Harding J., Ritter A., Rayasam A., Fabry Z., Sandor M. 2015. Lymphangiogenesis is induced by Mycobacterial granulomas via vascular endothelial growth factor receptor-3 and supports systemic T-cell responses against Mycobacterial antigen. American Journal of Pathology, 185, 432–445 CrossrefWeb of ScienceGoogle Scholar

  • Ho W.E., Peha H.Y., Chan T.K., Wong W.S.F. 2014. Artemisinins: Pharmacological actions beyond anti-malarial. Pharmacology and Therapeutics, 142, 126–139. CrossrefGoogle Scholar

  • Jiraungkoorskula W., Sahaphonga S., Sobhonc P., Riengrojpitaka S., Kangwanrangsan N. 2005. Effects of praziquantel and artesunate on the tegument of adult Schistosoma mekongi harboured in mice. Parasitology International, 54, 177–183. CrossrefPubMedGoogle Scholar

  • Kato T., Ito Y., Hosono K., Suzuki T., Tamaki H., Minamino T., et al. 2011. Vascular Endothelial Growth Factor Receptor-1 Signaling Promotes Liver Repair through Restoration of Liver Microvasculature after Acetaminophen Hepatotoxicity. Toxicological Sciences 120, 218–229. CrossrefWeb of ScienceGoogle Scholar

  • Keiser J., Utzinger J. 2012. Antimalarials in the treatment of schistosomiasis. Current Pharmaceutical Design 18, 3531–3538PubMedGoogle Scholar

  • Lai W.K., Adams D.H. 2005. Angiogenesis and chronic inflammation; the potential for novel therapeutic approaches in chronic liver disease. Journal of Hepatology, 42, 7–11. http://dx.doi.org/10.1016/j.jhep.2004.11.008PubMedCrossref

  • Li Q., Weina P., Hickman M. 2013. The Use of Artemisinin Compounds as Angiogenesis Inhibitors to Treat Cancer. Cardiology and Cardiovascular Medicine “Research Directions in Tumor Angiogenesis”, (Ed.) Jianyuan Chai, Chapter7 ISBN 978-953-51-0963-1 http://dx.DOI.org/10.5772/54109Crossref

  • Liang Y.S., Bruce J.I., Boyd D.A. 1987. Laboratory cultivation of schistosome vector snails and maintenance of schistosome life cycles. Proc First Sino-Am Symp, 1, 34–48Google Scholar

  • Loeffler D.A., Lundy S.K., Singh K.P., Gerard H.C., Hudson A.P., Boros D.L. 2002. Soluble egg antigens from Schistosoma mansoni induce angiogenesis-related processes by up-regulating vascular endothelial growth factor in human endothelial cells. Journal of Infectious Diseases, 185, 1650–1656. CrossrefGoogle Scholar

  • Mantovani A., Schioppa T., Porta C., Allavena P., Sica A. 2006. Role of tumor-associated macrophages in tumor progression and invasion. Cancer Metastasis Reviews, 25, 315–322. CrossrefPubMedGoogle Scholar

  • Neuman M.G., Benhamou J.P., Marcellin P, et al. 2007. Cytokine–chemokine and apoptotic signatures in patients with hepatitis C. Translational Research, 149, 126–136. CrossrefWeb of ScienceGoogle Scholar

  • Nurden A. 2011. Platelets, inflammation and tissue regeneration. Thrombosis and Haemostasis, 105 (Suppl 1), S13–33. CrossrefWeb of ScienceGoogle Scholar

  • Ono M. 2008. Molecular links between tumor angiogenesis and inflammation: inflammatory stimuli macrophages and cancer cells as targets for therapeutic strategy. Cancer Science, 99, 1501–1506. CrossrefPubMedWeb of ScienceGoogle Scholar

  • Pusztaszeri M.P., Seelentag W., Fred T., Bosman F.T. 2006. Immunohistochemical expression of endothelial markers CD31, CD34, von Willebrand factor, and Fli-1 in normal human tissues. Journal of Histochemistry & Cytochemistry, 54, 385–395CrossrefGoogle Scholar

  • Ren S., Abuel-Haija M., Khurana J.S., Zhang X. 2011. D2-40: an additional marker for myoepithelial cells of breast and the precaution in interpreting tumor lymphovascular invasion. International Journal of Clinical and Experimental Pathology, 4, 175–182Google Scholar

  • 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 Egyptian Society of Parasitology, 33, 597–614Google Scholar

  • Tsuji N., Ishiguro S., Sasaki Y. and Kudo M. 2013. CD34 expression in noncancerous liver tissue predicts multicentric recurrence of hepatocellular carcinoma. Journal of Digestive Diseases, 31, 467–71. CrossrefGoogle Scholar

  • Van Kruiningen H.J., Hayes A.W., Colombel J.F. 2014. Granulomas obstruct lymphatics in all layers of the intestine in Crohn’s disease. APMIS, 122, 1125–9. CrossrefPubMedWeb of ScienceGoogle Scholar

  • Verheul H.M., Pinedo H.M. 2000. The role of vascular endothelial growth factor (VEGF) in tumor angiogenesis and early clinical development of VEGF-receptor kinase inhibitors. Clinical Breast Cancer, 1(Suppl 1), S80–4CrossrefGoogle Scholar

  • Wang J., Zhang B., Guo Y., Li G., Xie Q., Zhu B., et al. 2008. Artemisinin inhibits tumor lymphangiogenesis by suppression of vascular endothelial growth factor C. Pharmacology, 82, 148–155. CrossrefWeb of SciencePubMedGoogle Scholar

  • World Health Organization 2016. Schistosomiasis. http://www.who.int/mediacentre/factsheets/fs115/ena.

  • Yan Z., Qu K., Zhang J., Huang Q., Qu P., Xu X., et al. 2015. CD147 promotes liver fibrosis progression via VEGF-A/VEGFR2 signalling-mediated cross-talk between hepatocytes and sinusoidal endothelial cells. Clinical Science, 129, 699–710; CrossrefWeb of ScienceGoogle Scholar

  • Yokomor H., Oda M., Kaneko F., Kawachi S., Tanabe M., Yoshimura K., et al.T. 2010. Lymphatic marker podoplanin/D2-40 in human advanced cirrhotic liver- Re-evaluations of microlymphatic abnormalities. BMC Gastroenterology, 10, 131. CrossrefWeb of SciencePubMedGoogle Scholar

  • Zhang Z., Yu S., Miao L., Huang X., Zhang X., Zhu Y. 2008. Artesunate combined with vinorelbine plus cisplatin in treatment of advanced non-small cell lung cancer: a randomized controlled trial. Chinese Journal of Integrative Medicine, 6, 134–138. CrossrefGoogle Scholar

About the article

Received: 2016-12-08

Revised: 2017-06-27

Accepted: 2017-06-28

Published Online: 2017-10-15

Published in Print: 2017-12-20


Conflicts of Interest(s) Authors declare that there is no conflict of interest regarding the publication of this paper.

Financial and funding statement This work funded and financially supported on the expenses of the authors.


Citation Information: Acta Parasitologica, Volume 62, Issue 4, Pages 708–716, ISSN (Online) 1896-1851, ISSN (Print) 1230-2821, DOI: https://doi.org/10.1515/ap-2017-0085.

Export Citation

© 2017 W. Stefański Institute of Parasitology, PAS. Copyright Clearance Center

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Naglaa Fathy Abd El-Aal, Rania Said Hamza, and Ola Harb
Experimental Parasitology, 2017, Volume 183, Page 23

Comments (0)

Please log in or register to comment.
Log in