title: Dose-response inhibition of proteolytic activity by a cysteine protease inhibitor in a murine model of fasciolosis.
abstract: Using the film in situ zymography (FIZ) technique, it has been demonstrated that N-[N-(L: -3-trans-carboxyoxirane-2-carbonyl)-L: -leucyl]-agmatine (E-64) inhibits Fasciola hepatica proteolytic activity in vivo. The aim of this study was to establish the dose-response relationship of the inhibition of proteolysis as assessed by FIZ with E-64 at different dosages in a murine model of fasciolosis. Maximum effective inhibition of proteolysis was achieved at 50 mg/kg/day (87%). Mice treated with this dose survived for a mean of 10.92 days more than untreated controls, and their ova counts and egg viability were significantly (P<0.05) lower than this latter group. These results indicate that intraperitoneal administration of E-64 not only inhibited liver proteolytic activity in a dose-dependent manner but also produced anti-fecundity and anti-embryonation effects, delaying the progression of fasciolosis. Yet, residual proteolysis may suggest that other E-64-non-sensitive enzymes are involved, or that E-64-enzyme chemical interactions are only capable of a partial agonistic-like effect.
authors.affiliation: Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Mexico, D.F. 04510, Mexico. yalcala@prodigy.net.mxa
authors.forename: Yazmin
authors.initials: Y
authors.lastname: Alcalá-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; D002470:Cell Survival; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005210:Fasciola hepatica / Q000187:drug effects* / Q000201:enzymology; D005211:Fascioliasis / Q000188:drug therapy* / Q000469:parasitology; D005298:Fertility; D007274:Injections, Intraperitoneal; D007930:Leucine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008099:Liver / Q000469:parasitology; D051379:Mice; D010270:Parasite Egg Count; D016019:Survival Analysis
chemical_list: D015853:Cysteine Proteinase Inhibitors; D003546:Cysteine Endopeptidases; D007930:Leucine; C024974:E 64