title: Evidence of 14C-furazolidone metabolite binding to the hepatic DNA of trout.
abstract: Furazolidone (FZ) is a nitrofuran drug commonly used in aquaculture. In the present study, [methylidene-14C]-FZ or [oxazolone-4,5-14C]-FZ was offered to rainbow trout (Oncorhyncus mykiss) in medicated feed at a daily dose of 135 mg/kg b. wt. for 10 days. The trout were sacrificed at specific time points post-dosing and the liver removed for DNA-bound 14C characterization. Both forms of the 14C-labelled FZ were converted by trout to reactive metabolite(s) which bound irreversibly to the hepatic DNA. The amount of 14C bound to the hepatic DNA increased with post-dosing time and was higher in trout pretreated with [methylidene-14C]-FZ than in trout pretreated with [oxazolone-4,5-14C]-FZ. The identity of the FZ reactive metabolite(s) remained to be elucidated. However, a part of the FZ reactive metabolite(s) could be released as 3-amino-2-oxazolidone by acid hydrolysis. An appreciable amount of 14C was also found to bind irreversibly with the hepatic DNA of trout following an i.v. injection of [oxazolone-4,5-14C]-FZ. Results of these studies indicate that FZ is metabolized by trout to a reactive metabolite(s) which binds irreversibly to the DNA of trout liver.
authors.affiliation: Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Meng
authors.forename: S S
authors.initials: SS
authors.lastname: Mangat
authors.forename: I P
authors.initials: IP
authors.lastname: Grudzinski
authors.forename: F C
authors.initials: FC
authors.lastname: Law
mesh_terms: D000821:Animal Feed; D000818:Animals; D000890:Anti-Infective Agents / Q000378:metabolism*; D017756:Aquaculture; D002250:Carbon Radioisotopes / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D005503:Food Additives / Q000378:metabolism; D005664:Furazolidone / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D017686:Oncorhynchus mykiss / Q000378:metabolism*
chemical_list: D000890:Anti-Infective Agents; D002250:Carbon Radioisotopes; D005503:Food Additives; D005664:Furazolidone; D004247:DNA