Effects of dietary pantethine levels on drug-metabolizing system in the liver of rats orally administered varying amounts of autoxidized linoleate.

Abstract

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

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

“…Figure 4 shows that the cytochrome P-450 content in rat liver microsomes increased at first (induction period) and then decreased (reduction period) by the consecutive oral dose of AL for 15 days. Now we can better explain the incompatible phenomena reported previously (5,6) for the changes in cytochrome P-450 content by repeated AL administration. The increase and the decrease of cytochrome P-450 content by repeated AL administration previously reported probably corresponds to observations in the induction and reduction periods, respectively.…”

Effects of dose levels of autoxidized linoleic acid on the drug-metabolizing system in rat liver.

“…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.…”

Effects of dietary pantethine levels on contents of fatty acids and thiobarbituric acid reactive substances in the liber of rats orally administered varying amounts of autoxidized linoleate.

“…In the present study, we determined the changes in contents and compositions of fatty acids and TBA values in liver and the S-9 fraction obtained from rats raised under the same condition as described previously (3).…”

“…It has been found that both the content of cytochrome P-450 and the activity of the drug -metabolizing system were increased by a low dose of AL, and were decreased by a high dose of AL (1) or by the elongation of the dose period even in the case of a low dose of AL (2). We have also investigated the effects of dietary pantethine levels on the drug-metabolizing system in the livers of rat given a low or a high dose of AL (3) . That is, they were induced by the low dose of AL for 5 successive days and lowered by the high dose of AL for the same period, compared with respective non-AL groups in each of the three pantethine levels.…”

“…Thus, fatty acid contents and TBA values are determined with liver homogenates and the S-9 fraction including drug-metabolizing system on the same experimental conditions as the previous report (3 -excess groups was observed either in the intakes of diet and water or in the body weight of rats, but the pantethine-deficient groups was significantly different from pantethine-adequate and -excess groups with regard to the intakes of diet and water, and the body weight of rats. pantethine-deficient rats also scattered vigorously the diet after 20 days of the prefeeding.…”