USE OF PIG HEPATOCYTES TO STUDY THE INHIBITION OF MONOAMINE-OXIDASE BY FURAZOLIDONE

Primary cultures of pig hepatocytes were used to examine the irreversible inhibition of monoamine oxidase (MAO), which has been observed in tissues of a number of different animal species after oral treatment with furazolidone. The rapid biotransformation of the MAO substrate p-tyramine by intact cells could effectively and irreversibly be inhibited with the known MAO inhibitors iproniazid and clorgyline. Incubation of cells with beta-hydroxyethylhydrazine and also 3-amino-2-oxazolidinone, which were previously proposed as the metabolites of furazolidine responsible for the in vivo effect, resulted in an irreversible inhibition of the MAO activity. Incubation of cells with furazolidone also resulted in a dose-related inhibition, but this effect was completely reversible on withdrawal of the drug. A similar MAO inhibition was observed after treatment of cells with nitrofurazone and furaltadone but not with nitrofurantoin. The results obtained with intact cells were confirmed by studies with 13,000 g pellets of homogenates made from cells preincubated for 24 hr with the compounds, which showed an irreversible inhibition in the case of iproniazid and 3-amino-2-oxazolidinone, but not in the case of furazolidone. The present study shows that hepatocytes are capable of transforming 3-amino-2-oxazolidinone, but not furazolidone itself, into a potent irreversible type of MAO inhibitor.