Effect of autoxidized linoleic acid on the contents of cytochrome P-450 and cytochrome b5, and drug-metabolizing enzyme activities in rat liver.
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.
D015073:2-Acetylaminofluorene / Q000378:metabolism; D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003573:Cytochrome b Group / Q000378:metabolism*; D015786:Cytochromes b5; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology*; D008099:Liver / Q000033:anatomy & histology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009929:Organ Size / Q000187:drug effects; D010084:Oxidation-Reduction; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D003573:Cytochrome b Group; D008041:Linoleic Acids; D004364:Pharmaceutical Preparations; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D019787:Linoleic Acid; D015073:2-Acetylaminofluorene; D000633:Aminopyrine N-Demethylase