Binding of ¹⁴C‐furazolidone metabolites to the muscular and hepatic proteins of trout∗

Portions of the work were presented at the Annual Meeting of the American Society of Pharmacology and Experimental Therapeutics (Pharmacology 92), Orlando, Florida, USA, May, 1992.

Abstract

A high level of ¹⁴C was found to bind irreversibly with the liver proteins of rainbow trout (Oncorhyncus mykiss) exposed to 135 mg/kg bodyweight of ¹⁴C‐labelled furazolidone (¹⁴C‐FZ) in fish feed daily for 10 days. After the cessation of ¹⁴C‐FZ treatment, hepatic protein‐bound ¹⁴C in trout stayed high for at least 30 days. The chemical identity of protein‐bound ¹⁴C remained to be elucidated. However, a part of the protein‐bound ¹⁴C in the liver and muscle could be released as 3‐amino‐2‐oxazolidinone by acid hydrolysis. The formation of protein‐bound ^I4C in the liver was investigated further with trout dosed intravenously with different ¹⁴C‐FZ doses at 10°C or with 5 mg/kg FZ at different water temperatures. ¹⁴C binding to the liver proteins was found to increase with increasing FZ dose or water temperature. Results of these studies indicate that protein‐bound ¹⁴C in the muscle and liver of trout is related to the formation of reactive intermediates from FZ. However, additional studies on the identities of the protein‐bound FZ residues are required before they can serve as useful biomarkers to monitor FZ exposure in farm fish.

Keywords:

• furazolidone metabolites
• covalent binding
• trout

Notes

To whom correspondence should be addressed.

Present address: Department of Molecular Biology, PO Box 3944, University of Wyoming, Laramie, Wyoming 82071–3944, USA.

Portions of the work were presented at the Annual Meeting of the American Society of Pharmacology and Experimental Therapeutics (Pharmacology 92), Orlando, Florida, USA, May, 1992.