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Autoxidized linoleic acid (AL) having 800 meq/kg of peroxide value and 1,700 meq/kg of carbonyl value was given in repeated oral doses for 1-15 days at a daily dose of 2.5 ml/kg to male Wistar rats. During the administration, the effect of AL on drug-metabolizing activity was investigated periodically in liver microsomes. The contents of cytochrome P-450 and b5 were increased by consecutive oral doses for 3-7 days. Thereafter, the amount of cytochrome P-450 decreased gradually, but the b5 decreased slightly. Thus, after administration for 11-15 days, the cytochrome P-450 content was significantly lower but the cytochrome b5 content was rather high in comparison with the control group. The aminopyrine-N-demethylase activity was not reduced even after repeated oral doses of AL for 15 days. The activation of 2-acetyl amino fluorene (2-AAF), which the authors termed S-9 activity, gradually decreased during administration for more than 3 days, and completely disappeared after administration for 9 days.

Effect of autoxidized linoleic acid on the contents of cytochrome P-450 and cytochrome b5, and drug-metabolizing enzyme activities in rat liver.