INFLUENCE OF LONG-TERM ETHANOL TREATMENT ON RAT-LIVER ANILINE AND P-NITROPHENOL HYDROXYLATION

The present study investigates the influence of long-term ethanol (EtO H) 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-nit rophenol hydroxylation. Total P450 per liver was stimulated after EtOH treatment for 1, 4, and 12 weeks. In the case of longer EtOH treatmen t no additional stimulation in P450 content was observed. Aniline and p-nitrophenol hydroxylase activity increased in direct relation with t he duration of EtOH consumption. The stimulation of both enzymatic act ivities was different. In comparison to controls, in rats treated with 10% (v/v) EtOH for 1, 4, 12, and 36 weeks, an increase in nitrocatech ol 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 afte r 1 and 4 weeks of EtOH consumption. Aniline hydroxylation increased a fter 12 and 36 weeks of EtOH treatment only. Addition of EtOH in vitro had an inhibitory effect on both aniline and p-nitrophenol hydroxylat ion. With liver microsomes from controls as well as EtOH-treated rats the inhibition of p-nitrophenol hydroxylation was competitive in natur e (K-i = 5.6 mM and K-i = 5.9 mM). In contrast, there was a competitiv e inhibition of aniline hydroxylation with liver microsomes from contr ols only. With microsomes from EtOH-treated rats a mixed inhibition wa s found.