Biotransformation of nitrosobenzene, phenylhydroxylamine, and aniline in the isolated perfused rat liver.
1. Haemoglobin-free single-pass perfusion of isolated rat liver with [14C]aniline, [14C]phenylhydroxylamine, and [14C]nitrosobenzene was carried out. 2. Perfusion with aniline revealed apparent enzyme kinetics for 4-aminophenol formation with Km = 144 microM, Vmax = 51 nmol/min per g liver wet; for 2-aminophenol Km = 144 microM, Vmax = 16 nmol/min per g; for acetanilide Km = 33 microM, Vmax = 25 nmol/min per g. Formation of phenylhydroxylamine and nitrosobenzene was observed at a rate of 1.5 nmol/min per g provided that these metabolites had been trapped within red cells. 3. Perfusion with phenylhydroxylamine displayed a metabolic pattern similar to aniline with apparent phenylhydroxylamine reduction kinetics of Km = 260 microM and Vmax = 600 nmol/min per g. In addition an acid-labile phenylhydroxylamine glucuronide was formed. 4. Perfusion with nitrosobenzene showed very rapid reduction to phenylhydroxylamine and to the metabolites observed with phenylhydroxylamine. In postmicrosomal supernatant, enzymic reduction of nitrobenzene by NADH and NADPH showed Km = 12 microM nitrosobenzene and Vmax = 5000 nmol/min per g. 5. Three per cent of nitrosobenzene was irreversibly bound to liver proteins. After 20 min perfusion with nitrosobenzene, 0.95 mumol of liver glutathione was lost per 10 mumol nitrosobenzene infused; 0.16 mumol of glutathione was released with effusate and bile, 0.46 mumol of glutathionesulphinanilide was produced, the rest, 0.33 mumol, may have formed mixed disulphides.[1]References
- Biotransformation of nitrosobenzene, phenylhydroxylamine, and aniline in the isolated perfused rat liver. Eyer, P., Kampffmeyer, H., Maister, H., Rösch-Oehme, E. Xenobiotica (1980) [Pubmed]
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