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Xenobiotica
the fate of foreign compounds in biological systems
Volume 13, 1983 - Issue 5
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Original Article

Formation and disposition of N-hydroxylated metabolites of aniline and nitrobenzene by isolated rat hepatocytes

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Pages 295-302 | Received 01 Dec 1982, Published online: 30 Sep 2009
 

Abstract

1. The formation and secretion of phenylhydroxylamine plus nitrosobenzene was studied in cultures of isolated rat hepatocytes after addition of aniline or nitrobenzene.

2. With aniline concn. up to 10mM, N-oxygenated metabolites were secreted linearly with time over 2h.

3. Phenobarbitone pretreatment in vivo for c. 5 d increased aniline N-hydroxylation by a factor of 2.8.

4. Nitrobenzene reduction by isolated rat hepatocytes, yielding phenylhydroxylamine plus nitrosobenzene in the medium, was stimulated 1.9-fold and 4.3-fold after phenobarbitone pretreatment in vivo for 5 and 10d, respectively.

5. After reduction of nitrobenzene by isolated hepatocytes, the secretion of N-oxygenated products into the medium was non-linear with time for substrate concn. higher than 2.5 mM, probably due to the formation of cytotoxic concn. of nitrosobenzene.

6. Isolated rat hepatocytes reduced phenylhydroxylamine to aniline.

7. Results indicate that isolated rat hepatocytes are a reliable and sensitive system to demonstrate N-oxygenated metabolites of aromatic amino- and reduction of nitro-compounds.

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