Evidence of 14C-furazolidone metabolite binding to the hepatic DNA of trout.

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.