The anthelmintic activity of 1,10-phenanthroline, a metalloenzyme inhibitor

DOI: 10.18805/ijar.B-3692    | Article Id: B-3692 | Page : 1518-1521
Citation :- The anthelmintic activity of 1,10-phenanthroline, a metalloenzyme inhibitor.Indian Journal Of Animal Research.2019.(53):1518-1521
Kavita Singh, A. Rehman, R. Ullah, L. Rehman, S. Wasim, F. Farhat, M.A. Beg and S.M.A. Abidi a.abidi92@gmail.com
Address : Section of Parasitology, Department of Zoology, Aligarh Muslim University, Aligarh-202 002, Uttar Pradesh, India.
Submitted Date : 18-07-2018
Accepted Date : 20-10-2018

Abstract

Paramphistomosis is a chronic, debilitating parasitic disease of livestock prevalent in the tropical and sub-tropical countries. Globally there is a heavy reliance on anthelmintics but concerns over drug resistance encourage the search for new leads. Metalloproteinases play a significant role in the biology and life cycle of parasitic helminths. The efficacy of metalloproteinase inhibitor, 1,10-Phenanthroline (1,10-phe) which is commonly used as a specific enzyme inhibitor in biochemical assays, was tested in vitro on Gigantocotyle explanatum tegument as a marker of anthelmintic action. The scanning electron microscopy revealed that the tegumental surface exhibited considerable changes in the worms treated with the metalloenzyme inhibitor, 1,10-phe. The untreated control worms appeared normal showing smooth tegumental surface with abundant dome shaped papillae in the anterior to mid region, while their density was less around the acetabulum which serves as a hold-fast organ helping the worms to remain attached in biliary passage. The 1,10-phe produced significant tegumental damage when the liver amphistomes were in vitro exposed to this compound at 12.5 µM concentration. The surface changes appeared in the form of edematous ridges with prominent furrows and erosion of the dome shaped papillae with rosette shaped deep lesions as a result of which deep parenchymatous tissues were exposed. The collapse of sensory bulbs as well as sloughing of tegument, particularly in the anterior-mid region was observed. The nature of damage could be comparable to various anthelmintics used in previous studies. To the best of our knowledge this is the first report of direct exposure of amphistome worms to zinc metallo-enzyme inhibitor, however, further in vivo studies are required to ascertain the anthelmintic efficacy of 1,10-phe.

Keywords

1-10-phenanthroline Anthelmintic Gigantocotyle explanatum Tegumental topography.

References

  1. Acosta D, Goni F, Carmona C (1998) Characterization and partial purification of a leucine aminopeptidase from Fasciola hepatica. J Parasitol 84: 1-7.
  2. Ahmad M, Nizami WA, Hanna REB (1987) Gigantocotyle explanatum: Scanning electron microscopic studies on the topographical effects of certain anthelmintics in vitro Int J Parasitol 17(7): 1287-1296.
  3. Amiri P, Sakanari J, Basch P, Newport G, McKerrow JH (1988) The Schistosomatium douthitti cercarial elastase is biochemically and structuraly distinct from that of Schistosoma mansoni. Mol Biochem Parasitol 28(2): 113-20.
  4. Bonaldo MC, d’Escoffier LN, Salles JM, Goldenberg S (1991) Characterization and expression of proteases during Trypanosoma cruzi metacyclogenesis. Exp Parasitol 3: 44-51.
  5. Castedo L, Tojo G (1990) The alkaloids: Chemistry and pharmacology, Chapter 3 In: Brossi A.(ed.) Phenanthrene Alkaloids, Academic Press, pp 33-99.
  6. Davies C (1979) The forebody glands and surface features of the metacercariae and adults of Microphallus similis. Int J Parasitol 9: 553-564
  7. Day TA, Chen GZ (1998) The metalloprotease inhibitor 1,10-phenanthroline affects Schistosoma mansoni motor activity, egg laying and viability. Parasitology 116: 319-325.
  8. Fairweather I, Threadgold LT, Hanna REB (1999) Development of Fasciola hepatica in the mammalian host. In: Dalton JP (ed) Fascioliasis. CAB International, Wallingford, pp 47-111.
  9. Geurts N, Opdenakker G, Steen PEVD (2012) Matrix metalloproteinases as therapeutic targets in protozoan parasitic infections. Pharmacol Ther 133: 257-279.
  10. Hotez P, Haggerty J, Hawdon J, Milstone L, Gamble HR, Schad G, Richard F (1990) Metalloproteases of infective Ancyclostoma hookworm larvae and their possible functions in tissue invasion and ecdysis. Infect Immun 58: 3883-3892.
  11. Keiser J, Utzinger J, Xiao S, Odermatt P, Tesana S (2007) Opisthorchis viverrini: Efficacy and tegumental alterations following administration of tribendimidine in vivo and in vitro. Parasitol Res 102(4): 771-776.
  12. Khan MAH, Ullah R, Rehman A, Rehman L, Shareef PAA, Abidi SMA (2017) Immunolocalization and immunodetection of the excretory/    secretory (ES) antigens of Fasciola gigantica. PLoS ONE 12(10): e0185870. 
  13. Lai SC, Jiang ST, Chen KM, Lee H.H (2005) Matrix metalloproteinases activity demonstrated in the infective stage of the nematodes, Angiostrongylus cantonensis. Parasitol Res 97:466-471.
  14. Lane JE, Bogitsh BJ, Ribeiro-Rodrigues R, Kral MV, Jones MM, Carter CE (1998) Ultrastructural effects of the chelating agent 1,10-    phenanthroline on Trypanosoma cruzi epimastigotes in vitro. Parasitol Res 84:399-402.
  15. Manoharan R, Selvakumar KN, Pandian ASS (2003) Constraints in milk production faced by the farmers in Pondicherry Union Territory. Indian J Anim Res. 37(1):68-70.
  16. Marco M, Nieto A (1991) Metalloproteinases in the larvae of Echinococcus granulosus. Int J Parasitol 2(6):743-746.
  17. McCarthy E, Stacka C, Donnelly SM, Doyle S, Mann VH, Brindley PJ, Stewart M, Day TA, Maule AG, Dalton JP (2004) Leucine aminopeptidase of the human blood flukes, Schistosoma mansoni and Schistosoma japonicum. Int J Parasitol 34:703-714.
  18. Pal M (2005) Importance of zoonoses in public health. Indian J Anim Res 75. 586-591.
  19. Pokharel DR, Rai R, Kumar P, Chaturvedi CM, Rathaur S (2006) Tissue localization of collagenase and leucine aminopeptidase in the bovine filarial parasite Setaria cervi. Filarial Journal 5:7.
  20. Rascon JAA, Mckerrow JH (2013) Synthetic and natural protease inhibitors provide insights into parasite development, virulence and pathogenesis. Current Med Chem 20: 3078-3102.
  21. Rehman A, Ullah R, Jaiswal N, Khan MAH, Rehman L, Beg MA, Malhotra SK, Abidi SMA (2017) Low virulence potential and in vivo transformation ability in the honey bee venom treated Clinostomum complanatum. Exp Parasitol 183: 33-40.
  22. Rhoads ML, Fetterer RH (1998) Purification and characterization of a secreted aminopeptidase from adult Ascaris suum. Int J Parasitol 28: 1681-1690.
  23. Rizvi A, Fatima T, Shareef PAA, Saifullah MK, Bano B, Saleemuddin M, Abidi SMA (2010) Preliminary analysis of in vitro released excretory/secretory (E/S) cysteine proteases of the progenetic metacercariae of Clinostomum complanatum. XII ICOPA, Melbourne, Australia 187-191.
  24. Salvesen GS, Nagase H (2001) Inibition of proteolytic enzymes. In: Proteolytic enzymes: a practical approach, 2nd ed: 105-130.
  25. Sammes PG, Yahioglu GY (1994) 1,10-phenanthroline: a versatile ligand. Chem Soc Rev 23: 327-334.
  26. Seay MB, Heard PL, Chaudhuri G (1996) Surface Zn-proteinase as a molecule for defense of Leishmania mexicana amazonensis promastigotes against cytolysis inside macrophage phagolysosomes. Infect Immun 64(12): 5129-5137.
  27. Shareef PAA, Brennan GP, McVeigh P, Khan MAH, Morphew RM, Mousley A, Marks NJ, Saifullah MK, Brophy PM, Maule AG, Abidi SMA. (2014) Time-dependent tegumental surface changes in juvenile Fasciola gigantica in response to triclabendazole treatment in goat. Acta Trop 136: 108-117.
  28. Singh M, Chauhan A and Garg MK (2007) Studies on housing and health care management practices followed by dairy owners. Indian J Anim Res 41(2):79-86.
  29. Ullah R, Rehman A, Zafeer MF, Rehman L, Khan YA, Khan MAH, Khan SN, Khan AU, SMA Abidi (2017) Anthelmintic potential of thymoquinone and curcumin on Fasciola gigantica. PLoS ONE 12(2): e0171267.
  30. Williamson AL, Lustigman S, Oksov Y, Deumic V, Plieskatt J, Mendez S, Zhan B, Bottazzi ME, Hotez PJ, Loukas A (2006) Ancylostoma caninum MTP-1, an astacin-like metalloprotease secreted by infective hookworm larvae, is involved in tissue migration. Infect Immunol 74(2): 961-967.
  31. Xu YZ, Dresden MH (1986) Leucine aminopeptidase and hatching of Schistosoma mansoni eggs. J Parasitol 72(4): 507-511.
  32. Yao C (2010) Major surface protease of trypanosomatids: one size fits all? Infect Immunol 78: 22-31. 

Global Footprints