Effects of dose levels of autoxidized linoleic acid on the drug-metabolizing system 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 at a daily dose of 0 (control)--7.5 ml/kg to male Wistar rats for 5 successive days. The effect of increasing AL dose on the drug-metabolizing system was investigated in rat liver microsomes and S-9 fractions. All the rats of a daily dose of 5.0-7.5 ml/kg died after the third day of consecutive oral doses. The cytochrome P-450 and b5 contents, enzyme activities in electron transfer system, aminopyrin-N-demethylase activity and S-9 activity (metabolic activation of 2-acetylaminofluorene) in the drug-metabolizing system changed essentially in a similar manner, that is, both the contents and the activities were increased by a small dose of AL, and were decreased by a large dose of AL. These results strongly supported the findings in a previous report wherein we observed the periodical effect of AL dose on the drug-metabolizing system.
Hiramatsu
N
N
Himeji Women's College, Japan.
Kishida
T
T
Natake
M
M
D015073:2-Acetylaminofluorene / Q000378:metabolism; D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003573:Cytochrome b Group / Q000378:metabolism; D015786:Cytochromes b5; D004305:Dose-Response Relationship, Drug; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
D003573:Cytochrome b Group; D008041:Linoleic Acids; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D019787:Linoleic Acid; D015073:2-Acetylaminofluorene; D000633:Aminopyrine N-Demethylase