scholarly journals The effects of unsaturated fatty acids on hepatic microsomal drug metabolism and cytochrome P-450

1969 ◽  
Vol 115 (3) ◽  
pp. 547-554 ◽  
Author(s):  
Richard P. Di Augustine ◽  
James R. Fouts
Keyword(s):  
Fatty Acids ◽  
Linoleic Acid ◽  
Rat Liver ◽  
Unsaturated Fatty Acids ◽  
Liver Microsomes ◽  
Type I ◽  
Rat Liver Microsomes ◽  
Microsomal Metabolism ◽  
Nitrobenzoic Acid

1. The effects of unsaturated fatty acids on drug-metabolizing enzymes in vitro were measured by using rat and rabbit hepatic 9000g supernatant fractions. 2. Unsaturated fatty acids inhibited the hepatic microsomal metabolism of ‘type I’ drugs with inhibition increasing with unsaturation: arachidonic acid>linolenic acid>linoleic acid>oleic acid. Inhibition was independent of lipid peroxidation. Linoleic acid competitively inhibited the microsomal O-demethylation of p-nitroanisole and the N-demethylation of (+)-benzphetamine. 3. The hepatic microsomal metabolism of ‘type II’ substrates, aniline and (−)-amphetamine, was not affected by unsaturated fatty acids. 4. The rate of reduction of p-nitrobenzoic acid and Neoprontosil was accelerated by unsaturated fatty acids. 5. Linoleic acid up to 3·5mm did not decelerate the generation of NADPH by rat liver soluble fraction, nor the activity of NADPH–cytochrome c reductase of rat liver microsomes. Hepatic microsomal NADPH oxidase activity was slightly enhanced by added linoleic acid. 6. No measurable disappearance of exogenously added linoleic acid occurred when this fatty acid was incubated with rat liver microsomes and an NADPH source. 7. The unsaturated fatty acids used in this study produced type I spectra when added to rat liver microsomes, and affected several microsomal enzyme activities in a manner characteristic of type I ligands.

Synthesis of molecular classes of cytidine diphosphate diglyceride by rat liver in vivo and in vitro

1977 ◽  
Vol 55 (11) ◽  
pp. 1153-1158 ◽  
Author(s):  
W. Thompson ◽  
G. MacDonald
Keyword(s):  
Fatty Acids ◽  
Phosphatidic Acid ◽  
Rat Liver ◽  
Liver Microsomes ◽  
Phosphatidyl Inositol ◽  
Convincing Evidence ◽  
Rat Liver Microsomes ◽  
Cytidine Diphosphate

Cytidine diphosphate (CDP) diglyceride isolated from pooled rat liver was shown like phosphatidyl inositol to contain stearate and arachidonate as the major fatty acids. On the other hand palmitate and oleate were the predominant fatty acids of total liver phosphatidic acid.Labelling of molecular classes of phosphatidic acid, CDP-diglyceride, and phosphatidyl inositol was examined in liver at various time intervals after either intraportal or intrajugular injections of [3H]glycerol. In general the major flux of radioactivity was through the oligoenoic classes [Δ1 and Δ2] of phosphatidic acid. In contrast the labelling of oligoenoic classes of CDP-diglyceride was less and of polyenoic classes [Formula: see text] significantly enhanced, raising the possibility that there may be some discrimination in selection of species of phosphatidic acid for liponucleotide synthesis. After intrajugular injections of isotope the monoenoic classes of phosphatidyl inositol were most highly labelled but between 5 and 240 min there was a progressive decrease of radioactivity in this class and increase in the tetraenoic species, presumably as a result of deacylation and reacylation reactions. The backflow of radioactivity from phosphatidyl inositol was deemed not a likely explanation for the observed labelling pattern of CDP-diglyceride.The conversion of sonicated dispersions of [3H]phosphatidic acid, labelled in the glycerol moiety, to CDP-diglyceride by rat liver microsomes was examined. There was slightly less label in the oligoenoic classes and slightly more in trienoic and polyenoic (> Δ4) classes of CDP-diglyceride as compared with phosphatidic acid. These differences were much smaller in vitro than those observed in vivo. The in vitro data provide no convincing evidence for a high enough selectivity to explain the differences in arachidonate content between phosphatidic acid and the liponucleotide.

In vitro metabolism in Sprague–Dawley rat liver microsomes of forsythoside A in different compositions of Shuang–Huang–Lian

Fitoterapia ◽  
2011 ◽  
Vol 82 (8) ◽  
pp. 1222-1230 ◽  
Author(s):  
Wei Zhou ◽  
Liu-qing Di ◽  
Jin-jun Shan ◽  
Xiao-lin Bi ◽  
Le-tian Chen ◽  
...  
Keyword(s):  
Rat Liver ◽  
Liver Microsomes ◽  
In Vitro Metabolism ◽  
Rat Liver Microsomes ◽  
Sprague Dawley ◽  
Sprague Dawley Rat

scholarly journals In Vitro Characterization of Borneol Metabolites by GC--MS Upon Incubation with Rat Liver Microsomes

2008 ◽  
Vol 46 (5) ◽  
pp. 419-423 ◽  
Author(s):  
R. Zhang ◽  
C.-h. Liu ◽  
T.-l. Huang ◽  
N.-s. Wang ◽  
S.-q. Mi
Keyword(s):  
Rat Liver ◽  
Liver Microsomes ◽  
Rat Liver Microsomes ◽  
In Vitro Characterization

In Vitro Metabolism of E2, G2: Novel Bile Acid-Coupling Camptothecin Analogues, in Rat Liver Microsomes

2021 ◽  
Vol 16 ◽  
Author(s):  
Xiangli Zhang ◽  
Qin Shen ◽  
Yi Wang ◽  
Leilei Zhou ◽  
Qi Weng ◽  
...  
Keyword(s):  
Bile Acid ◽  
Phase I ◽  
Rat Liver ◽  
Deoxycholic Acid ◽  
Liver Microsomes ◽  
Intrinsic Clearance ◽  
Rat Liver Microsomes ◽  
Camptothecin Analogues

Background: E2 (Camptothecin - 20 (S) - O- glycine - deoxycholic acid), and G2 (Camptothecin - 20 (S) - O - acetate - deoxycholic acid) are two novel bile acid-derived camptothecin analogues by introducing deoxycholic acid in 20-position of CPT(camptothecin) with greater anticancer activity and lower systematic toxicity in vivo. Objective: We aimed to investigate the metabolism of E2 and G2 by Rat Liver Microsomes (RLM). Methods: Phase Ⅰ and Phase Ⅱ metabolism of E2 and G2 in rat liver microsomes were performed respectively, and the mixed incubation of phase I and phase Ⅱ metabolism of E2 and G2 was also processed. Metabolites were identified by liquid chromatographic/mass spectrometry. Results: The results showed that phase I metabolism was the major biotransformation route for both E2 and G2. The isoenzyme involved in their metabolism had some difference. The intrinsic clearance of G2 was 174.7mL/min. mg protein, more than three times of that of E2 (51.3 mL/min . mg protein), indicating a greater metabolism stability of E2. 10 metabolites of E2 and 14 metabolites of G2 were detected, including phase I metabolites (mainly via hydroxylations and hydrolysis) and their further glucuronidation products. Conclusion: These findings suggested that E2 and G2 have similar biotransformation pathways except some difference in the hydrolysis ability of the ester bond and amino bond from the parent compounds, which may result in the diversity of their metabolism stability and responsible CYPs(Cytochrome P450 proteins).

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