Artículo
Hepatic and extra-hepatic metabolic pathways involved in flubendazole biotransformation in sheep
Maté, María Laura
; Virkel, Guillermo Leon
; Lifschitz, Adrian Luis
; Ballent, Mariana
; Lanusse, Carlos Edmundo
Fecha de publicación:
09/2008
Editorial:
Pergamon-Elsevier Science Ltd
Revista:
Biochemical Pharmacology
ISSN:
0006-2952
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Flubendazole (FLBZ) is a broad-spectrum benzimidazole anthelmintic compound used in pigs, poultry and humans. Its potential for parasite control in ruminant species is under investigation. The objective of the work described here was to identify the main enzymatic pathways involved in the hepatic and extra-hepatic biotransformation of FLBZ in sheep. Microsomal and cytosolic fractions obtained from sheep liver and duodenal mucosa metabolised FLBZ into a reduced FLBZ metabolite (red-FLBZ). The keto-reduction of FLBZ led to the prevalent (∼98%) stereospecific formation of one enantiomeric form of red-FLBZ. The amounts of red-FLBZ formed in liver subcellular fractions were 3-4-fold higher (P < 0.05) compared to those observed in duodenal subcellular fractions. This observation correlates with the higher (P < 0.05) carbonyl reductase (CBR) activities measured in the liver compared to the duodenal mucosa. No metabolic conversion was observed following FLBZ or red-FLBZ incubation with sheep ruminal fluid. Sheep liver microsomes failed to convert red-FLBZ into FLBZ. However, this metabolic reaction occurred in liver microsomes prepared from phenobarbital-induced rats, which may indicate a cytochrome P450-mediated oxidation of red-FLBZ. A NADPH-dependent CBR is proposed as the main enzymatic system involved in the keto-reduction of FLBZ in sheep. CBR substrates such as menadione and mebendazole (a non-fluoride analogue of FLBZ), inhibited this liver microsomal enzymatic reaction, which may confirm the involvement of a CBR enzyme in FLBZ metabolism in sheep. This research is a further contribution to the understanding of the metabolic fate of a promissory alternative compound for antiparasitic control in ruminant species.
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Identificadores
Colecciones
Articulos(CCT - TANDIL)
Articulos de CTRO CIENTIFICO TECNOLOGICO CONICET - TANDIL
Articulos de CTRO CIENTIFICO TECNOLOGICO CONICET - TANDIL
Articulos(CIVETAN)
Articulos de CENTRO DE INVESTIGACION VETERINARIA DE TANDIL
Articulos de CENTRO DE INVESTIGACION VETERINARIA DE TANDIL
Citación
Maté, María Laura; Virkel, Guillermo Leon; Lifschitz, Adrian Luis; Ballent, Mariana; Lanusse, Carlos Edmundo; Hepatic and extra-hepatic metabolic pathways involved in flubendazole biotransformation in sheep
; Pergamon-Elsevier Science Ltd; Biochemical Pharmacology; 76; 6; 9-2008; 773-783
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