INVESTIGADORES
ALVAREZ Luis Ignacio
artículos
Título:
Potentiation of triclabendazole action in vivo against a triclabendazole-resistant isolate of Fasciola hepatica following its co-administration with the metabolic inhibitor, ketoconazole.
Autor/es:
DEVINE, C.; BRENNAN, G.; LANUSSE C.; ALVAREZ, L.; TRUDGETT, A.; HOEY, E.; FAIRWEATHER, I.
Revista:
VETERINARY PARASITOLOGY
Editorial:
ELSEVIER SCIENCE BV
Referencias:
Lugar: Amsterdam; Año: 2012 vol. 184 p. 37 - 47
ISSN:
0304-4017
Resumen:
An in vivo study in the laboratory rat model has been carried out to monitor morphological
changes in adult Fasciola hepatica over a 4-day period resulting from co-treatment
with triclabendazole (TCBZ) and ketoconazole (KTZ), a cytochrome P450 inhibitor. Rats
were infected with the triclabendazole-resistant Oberon isolate of F. hepatica, dosed orally
with triclabendazole at a dosage of 10 mg/kg live weight and ketoconazole at a dosage of
10 mg/kg live weight. Flukes were recovered at 24, 48, 72 and 96 h post-treatment (p.t.)
and changes to fluke ultrastructure were assessed using transmission electron microscopy
(TEM). Results showed an increase in the severity of changes to the fluke ultrastructure
with time p.t. Swelling of the basal infolds and the associated mucopolysaccharide
masses became more severe with time. Golgi complexes, if present, were greatly reduced
in size and number by 96 h p.t., and sub-tegumental flooding was seen from the 72 h timeperiod
onwards. Some sloughing of the tegumental covering over the spines was observed
at 96 h p.t. The results demonstrated that the Oberon isolate is more sensitive to TCBZ
action in the presence of KTZ than to TCBZ alone, reinforcing the idea that altered drug
metabolism is involved in the resistance mechanism. Moreover, they support the concept
that TCBZ + inhibitor combinations (aimed at altering drug pharmacokinetics and potentiating
the action of TCBZ) could be used in the treatment of TCBZ-R populations of F. hepatica.