Metabolism of sodium nifurstyrenate, a veterinary antimicrobial nitrofuran, in animals and fish.
Sodium nifursyrenate [beta-(5-nitro-2-furyl)-p-carboxystyrene sodium salt, NSA-Na] is an antibacterial nitrofuran which has been widely used for prevention and treatment of bacterial infections in fish in Japan. When NSA-Na was anaerobically incubated with rabbit liver cytosol and 2-hydroxypyrimidine, 1-(p-carboxyphenyl)-5-cyano-3-oxo-1,4-pentadiene (cyano-pentadienone), 1-(p-carboxyphenyl)-5-cyano-3-oxo-1-pentanone (cyano-pentanone), and 1-(p-carboxyphenyl)-5-cyano-3-pentanone (cyano-pentanone) were isolated and identified as the metabolites of the nitrofuran. In addition, when cyano-pentenone and cyano-pentanone were aerobically incubated with the liver preparation and NADPH, 1-(p-carboxyphenyl)-5-cyano-3-hydroxy-1-pentene (cyano-pentenol) and 1-(p-carboxyphenyl)-5-cyano-3-pentanol (cyano-pentanol) were also isolated and identified as the metabolites of the nitrofuran in its further metabolism, respectively. The anaerobic incubation of NSA-Na with rat liver cytosol and 2-hydroxypyrimidine resulted in the formation of cyano-pentadienone and cyano-pentanone. In this case, however, cyano-pentenone was not detectable. On the other hand, when NSA-Na was anaerobically incubated with sea bream liver cytosol and NADPH, the formation of cyano-pentenone, cyano-pentanone, and cyanopentenol, but not cyano-pentadienone, was observed. Furthermore, cyano-pentanone was metabolized to cyano-pentanol by the fish liver preparation with NADPH under aerobic conditions. When NSA-Na was given orally to rabbits, cyano-pentanone, cyano-pentenol, cyano-pentanol, and beta-(acetamido-2-furyl)-p-carboxystyrene (acetamidofuran) were identified as the urinary metabolites of the nitrofuran.(ABSTRACT TRUNCATED AT 250 WORDS)
Institute of Pharmaceutical Science, Hiroshima University School of Medicine, Japan.
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K
Tatsumi
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Kitamura
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M
Kato
K
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Hiraoka
D000818:Animals; D006224:Cricetinae; D003600:Cytosol / Q000378:metabolism; D005399:Fishes; D006168:Guinea Pigs; D008099:Liver / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D051379:Mice; D009152:Mutagenicity Tests; D009243:NAD / Q000378:metabolism; D009581:Nitrofurans / Q000378:metabolism* / Q000633:toxicity; D009602:Nitrosamines / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013343:Styrenes / Q000378:metabolism* / Q000633:toxicity
D009581:Nitrofurans; D009602:Nitrosamines; D013343:Styrenes; D009243:NAD; C075358:nifurstyrenic acid; C041199:N-nitrosoallyl-2,3-dihydroxypropylamine