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

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.