title: Comparative Metabolism of Thiabendazole in Cultured Hepatocytes from Rats, Rabbits, Calves, Pigs, and Sheep, Including the Formation of Protein-Bound Residues.
abstract: Cultured hepatocytes from rat, rabbit, calf, pig, and sheep were used to study metabolism and formation of protein-bound residues of thiabendazole ([(14)C]TBZ), a benzimidazole anthelmintic and fungicide. In all investigated species, major pathways corresponded to 5-hydroxylation of TBZ and its further conjugation. However, marked interspecies differences in rates of TBZ disappearance and 5-hydroxy metabolite formation were demonstrated. Rabbit hepatocytes presented the fastest TBZ biotransformation and were the most extensive hydroxylators. By contrast, the lowest capacity of oxidation was observed for the rat. Two unidentified minor metabolites, designated M1 and M2, were particularly produced by sheep hepatocytes. Moreover, the protein-bound residues in these cells, which could be related to cytochrome P450-dependent oxidation, were formed in 4 times greater amounts than in the other animal cells. These findings substantiate hepatocytes as an in vitro model for prediction of hepatic metabolism in vivo.
authors.affiliation: INRA, Laboratoire de Pharmacologie-Toxicologie, 180 Chemin de Tournefeuille, B.P. 3, 31931 Toulouse, France; State Institute for Quality Control of Agricultural Products (RIKILT-DLO), P.O. Box 230, 6700 AE Wageningen, The Netherlands; and Unidad de Hepatologia Experimental, Centro de Investigacion, Hospital La Fe, SVS Avenida Campanar 21, E-46009 Valencia, Spain.
authors.initials: M
authors.lastname: Coulet
authors.initials: C
authors.lastname: Eeckhoutte
authors.initials: G
authors.lastname: Larrieu
authors.initials: JF
authors.lastname: Sutra
authors.initials: LA
authors.lastname: Hoogenboom
authors.initials: MB
authors.lastname: Huveneers-Oorsprong
authors.initials: HA
authors.lastname: Kuiper
authors.initials: JV
authors.lastname: Castell
authors.initials: M
authors.lastname: Alvinerie
authors.initials: P
authors.lastname: Galtier