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T.A. Day and G.Z. Chen
Parasitology 116:319-325
The Zn2+-chelating metalloprotease inhibitor 1,10-phenanthroline
(phenanthroline, 5-150 uM) elicited dose-dependent contraction
of the longitudinal and circular (transverse) musculature of adult
male schistosomes. At the same concentrations, phenanthroline
did not cause contraction of dispersed individual muscle fibres.
The phenanthroline-induced contractions were reduced by the inclusion
of 100 or 300 uM Zn2+ in the extracellular medium. Phenanthroline
(05-150 uM) also inhibited the egg production of adult worm pairs
in vitro, with a 98% reduction at 50 uM. When worm pairs were
exposed to phenanthroline, the males detached from the dish and
released the females, resulting in unpaired worms. At the higher
concentrations (50 and 150 uM), the worms were killed in vitro.
Worm burdens were reduced by over 50% in infected mice injected
with phenanthroline (20 mg/kg/day for 4 days), but twice the dose
resulted in only a 25% reduction. Phenanthroline injections also
induced an hepatic shift and an unpairing of adult worms in infected
mice, and the female worms appeared degenerate and lacked gut
pigmentation. Mice fed a diet containing 0.3% phenanthroline received
significant protection from infection when challenged with schistosome
cercaria, where phenanthroline-fed mice had 94% fewer adult worms
than control mice. The broad range of phenanthroline effects on
schistosomes suggests broad and important functions for metalloproteases
in these worms.