SummaryAutoxidized linoleic acid (AL) having 800meq/kg of per oxide value and 1,700meq/kg of carbonyl value was given in repeated oral doses for 1-15 days at a daily dose of 2.5ml/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 cyto chrome 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 aminopyrin-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.

SummaryAutoxidized linoleic acid (AL) having 800meq/kg of per oxide value and 1,700meq/kg of carbonyl value was given in repeated oral doses at a daily dose of 0 (control)-7.5ml/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 5.0-7.5ml/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 fi ndings in a previous report wherein we observed the periodical effect of AL dose on the drug-metabolizing system. Key Words autoxidized linoleic acid, microsome, cytochrome P-450, cytochrome b5, electron transfer system, drug-metabolizing activity, aminopyrin-N-demethylase, S-9 activity, membrane disorder There have been some incompatible findings on the effect of autoxidized oil on drug-metabolizing activity in rat liver microsomes under the respective experimental conditions (1, 2). Therefore, in our previous work (3), AL having 800meq/kg of peroxide value and 1,700meq/kg of carbonyl value was administered periodically for 1-15 days at a daily dose of 2.5ml/kg body weight to male Wistar rats, and the effect of AL on the drug-metabolizing system in rat liver microsomes was studied. The cytochrome P-450 and b5 contents were increased by consecutive oral doses of AL for 3-7 days, then 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 97

SummaryThe effects of dietary pantethine levels on the drug metabolizing system were investigated under administration of varying amounts of autoxidized linoleate (AL) with rat liver microsomes and S-9 fractions. AL having 800 meq/kg of peroxide value and 1,700 meq/kg of carbonyl value was dosed to the rats of each group given drinking water containing 0mg% (deficient), 6.25mg% (normal), and 125mg% pan tethine (sufficient). The contents and activities of the enzymes in the drug metabolizing system in the rat liver of each pantethine-level group changed essentially in a similar manner, that is, they were induced at an AL daily dose of 0.2ml/100g body weight (i.e., small dose) for 5 successive days and lowered at a daily dose of 0.4ml/100g body weight (i.e., large dose) by the same administration period, compared with respective non -AL groups in each of the three pantethine levels. In both non-AL and the small-dose AL, enzyme activities of the electron transfer system in rat liver microsomes, aminopyrin-N-demethylase activity, and metabolic acti vation of 2-acetylaminofluorene in S-9 fractions were significantly higher in the pantethine-deficient group than in the pantethine-normal andsufficient groups. In the large-dose AL, the enzyme activities in the drug metabolizing system decreased significantly in any pantethine levels, though the survival rate of the rats was higher in the pantethine-sufficient group than in the pantethine-normal groups. The results suggest that the pantethine relieves the effect of dosed AL on the drug-metabolizing system in rat liver. Key Words autoxidized linoleic acid, microsome, cytochrome P-450, cytochrome b5, electron transfer system, drug-metabolizing activity, aminopyrin-N-demethylase, S-9 activity, pantethine 303

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SummaryThe effects of dietary pantethine levels on the contents and compositions of fatty acids and on the levels of lipid peroxides were investigated with rat liver and its S-9 fraction under administration of 0 (non), 0.2 (low dose), and 0.35ml (high dose) of autoxidized linoleate (AL) per 100g body weight of the rats per day for 5 days. AL having 800 meq/kg of peroxide value (PV) and 1,700meq/kg of carbonyl value (CV) was dosed to the rats of each group given drinking water containing 0 mg% (deficient), 6.25mg% (adequate), and 125mg% pantethine (excess). In the pantethine-deficient and -adequate groups, the contents of fatty acids both in the liver homogenate and in the S-9 fraction were corre spondingly decreased by increasing dose levels of AL, and the decrease was remarkable especially in the pantethine-deficient group, but was not significant in the pantethine-excess group even by a high dose of AL. Particularly, in the high dose of AL, the notable decreases of oleic acid (C18:1) contents in both the liver and the S-9 fraction were observed in rats of the pantethine-deficient and -adequate groups.The thiobarbituric acid (TBA) values in the liver homogenate and the S-9 fraction were increased correspondingly by increasing dose levels of AL, and the increases were repressed in the pantethine-excess group.