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

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Meng J, Mangat SS, Grudzinski IP, Law FC

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

Drug Metabol Drug Interact. 1998;14(4):209-19.

PubMed ID

10694929 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Furazolidone	DNA	Nucleotide	Humans	Yes	Cross-linking/alkylation	Details