INVESTIGADORES
VIRKEL Guillermo Leon
artículos
Título:
In vitro ruminal biotransformation of benzimidazole sulphoxide anthelmintics: Enantioselective sulphoreduction in sheep and cattle
Autor/es:
VIRKEL, G., LIFSCHITZ, A., PIS, A., LANUSSE, C.
Revista:
JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
Editorial:
WILEY-BLACKWELL PUBLISHING, INC
Referencias:
Año: 2002 vol. 25 p. 15 - 23
ISSN:
0140-7783
Resumen:
The comparative in vitro sulphoreduction of the (+) and (-) enantiomers
of albendazole sulphoxide (ABZSO) and oxfendazole (OFZ) by ruminal fluid
obtained from sheep and cattle, was investigated, under anaerobic
conditions, in this study. Ruminal fluid samples were obtained from
Holstein steers fitted with a permanent rumen fistula and from
Corriedale lambs via an oesophageal tube. Albendazole sulphoxide,
incubated as either the racemic (rac) mixture or as each individual
enantiomeric form, was extensively sulphoreduced to form albendazole
(ABZ) by ruminal fluid from both species. The concentrations of ABZ
formed at different incubation times were between 55 and 158% greater
after the incubation of cattle ruminal fluid with (+) ABZSO, compared
with that produced when (-) ABZSO was the incubated substrate.
Similarly, the concentrations of ABZ were 1.3--3.0-fold higher when (+)
ABZSO was incubated with sheep ruminal fluid. Significantly higher rates
of depletion were observed for the (+) enantiomeric form when ABZSO was
incubated with ruminal fluid from both species. The rates of ABZ
formation from both ABZSO enantiomeric forms were significantly higher
in sheep compared with cattle ruminal fluid. Fenbendazole (FBZ) was the
metabolite formed after the incubation of the racemic form of OFZ with
ruminal fluid obtained from both species. The metabolic profile of both
OFZ enantiomers followed a similar pattern to that observed for ABZSO
enantiomers. A bi-directional chiral inversion of one enantiomer into
its antipode was observed. The (+) enantiomer appeared in the incubation
medium when (-) ABZSO was the incubated substrate, and also the (-)
antipode was detected after (+) ABZSO incubation with ruminal fluid
obtained from both species. The results reported here demonstrate an
enantioselective ruminal sulphoreduction of ABZSO and OFZ (substrate
enantioselectivity). These findings contribute to interpret the chiral
behaviour of benzimidazole-sulphoxide anthelmintics.