Influence of long-term ethanol treatment on rat liver aniline and p-nitrophenol hydroxylation

The present study investigates the influence of long-term ethanol (EtOH) treatment of rats [10% (v/v) for 1, 4, 12, and 36 weeks] on hepatic microsomal cytochrome P450 (P450) content and liver aniline and p-nitrophenol hydroxylation. Total P450 per liver was stimulated after EtOH treatment for 1, 4, and 12 weeks. In the case of longer EtOH treatment no additional stimulation in P450 content was observed. Aniline and p-nitrophenol hydroxylase activity increased in direct relation with the duration of EtOH consumption. The stimulation of both enzymatic activities was different. In comparison to controls, in rats treated with 10% (v/v) EtOH for 1, 4, 12, and 36 weeks, an increase in nitrocatechol formation (1.1-, 1.2-, 2.2-, and 2.8-fold, respectively) was found. In contrast, no effect was observed on the metabolism of aniline after 1 and 4 weeks of EtOH consumption. Aniline hydroxylation increased after 12 and 36 weeks of EtOH treatment only. Addition of EtOH in vitro had an inhibitory effect on both aniline and p-nitrophenol hydroxylation. With liver microsomes from controls as well as EtOH-treated rats the inhibition of p-nitrophenol hydroxylation was competitive in nature (K-i = 5.6 mM and K-i = 5.9 mM). In contrast, there was a competitive inhibition of aniline hydroxylation with liver microsomes from controls only. With microsomes from EtOH-treated rats a mixed inhibition was found.