title: Effect of a cysteine protease inhibitor on Fasciola hepatica (liver fluke) fecundity, egg viability, parasite burden, and size in experimentally infected sheep.
abstract: Fasciola hepatica secretes proteolytic enzymes during liver invasion. The present study examined the effects of the cysteine protease inhibitor Ep-475 on sheep considering the following variables: serum levels of aspartate aminotransferase, L-lactate dehydrogenase, and gamma-glutamyltransferase, liver fluke fecundity, egg viability, parasite burden, and size. Twenty-four male sheep were randomly allocated in four groups of six animals each as follows: group A was infected with F. hepatica metacercariae and treated with 50 mg/kg of Ep-475, group B was infected and untreated, group C was uninfected and treated, and group D was uninfected and untreated. All animals were euthanized 10 weeks after the experimental infection. Serum activities of enzymes in infected animals were significantly lower in Ep-475-treated sheep than in untreated controls, although liver damage was produced. No significant reduction in total worm burden was observed between treated and untreated sheep. However, there was a significant difference on the average size, structure development, ova counts, and egg viability of liver flukes from these two groups. Results showed that Ep-475 reduces liver damage due to fasciolosis and induces an impairment of liver fluke growth and fecundity. These effects pinpoint liver fluke proteases as potential targets for pharmacological intervention.
authors.affiliation: Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Mexico. yalcala@prodigy.net.mx
authors.forename: Yazmin
authors.initials: Y
authors.lastname: Alcala-Canto
authors.forename: Froylan
authors.initials: F
authors.lastname: Ibarra-Velarde
authors.forename: Hector
authors.initials: H
authors.lastname: Sumano-Lopez
authors.forename: Jesus
authors.initials: J
authors.lastname: Gracia-Mora
authors.forename: Aldo
authors.initials: A
authors.lastname: Alberti-Navarro
mesh_terms: D000818:Animals; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005210:Fasciola hepatica / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D005211:Fascioliasis / Q000188:drug therapy / Q000469:parasitology / Q000662:veterinary*; D005298:Fertility / Q000187:drug effects*; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D010063:Ovum / Q000187:drug effects*; D012756:Sheep; D012757:Sheep Diseases / Q000188:drug therapy / Q000469:parasitology*
chemical_list: D015853:Cysteine Proteinase Inhibitors; C032425:N-(N-(3-carboxyoxirane-2-carbonyl)leucyl)isoamylamine; D007930:Leucine