scholarly journals The conversion of exogenous retinol and related compounds into retinyl phosphate mannose by adult Brugia pahangi in vitro

1983 ◽  
Vol 214 (2) ◽  
pp. 367-376 ◽  
Author(s):  
J C W Comley ◽  
J J Jaffe
Keyword(s):  
Liver Microsomes ◽  
Beta Carotene ◽  
Synthetase Activity ◽  
Rat Liver Microsomes ◽  
Brugia Pahangi ◽  
Glycoprotein Synthesis ◽  
Absolute Requirement ◽  
Endogenous Lipid ◽  
Related Compounds

Adult Brugia pahangi took up and incorporated beta-carotene and free retinol in vitro. The uptake of retinol was 50 times greater than that of beta-carotene under similar incubation conditions. beta-Carotene was almost entirely metabolized, primarily to retinol. The metabolism of retinol by B. pahangi in vitro was less extensive, with a variety of retinoids tentatively identified, including retinyl phosphate (Ret-P), retinyl phosphate mannose (Ret-P-Man) and anhydroretinol as minor metabolites. B. pahangi microsomes were also shown to biosynthesize Ret-P-Man from exogenous Ret-P and GDP-mannose, but not from endogenous lipid acceptors alone. In this circumstance an unidentified lipid appeared to be mannosylated by B. pahangi. The rate of mannose transfer to exogenous Ret-P by B. pahangi microsomes was 150 pmol X min -1. (mg of protein) -1. Ret-P-Man synthetase activity from both B. pahangi and rat liver microsomes had an absolute requirement for bovine serum albumin and MnCl2, and occurred in the absence of detergent. The results suggest a biochemical role for vitamin A in B. pahangi, possibly in filarial glycoprotein synthesis.

scholarly journals Nontargeted Metabolomics by High-Resolution Mass Spectrometry to Study the In Vitro Metabolism of a Dual Inverse Agonist of Estrogen-Related Receptors β and γ, DN203368

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 776
Author(s):  
Sin-Eun Kim ◽  
Seung-Bae Ji ◽  
Euihyeon Kim ◽  
Minseon Jeong ◽  
Jina Kim ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Resolution ◽  
Human Liver ◽  
High Resolution Mass Spectrometry ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Rat Liver Microsomes ◽  
High Resolution Mass ◽  
Resolution Mass

DN203368 ((E)-3-[1-(4-[4-isopropylpiperazine-1-yl]phenyl) 3-methyl-2-phenylbut-1-en-1-yl] phenol) is a 4-hydroxy tamoxifen analog that is a dual inverse agonist of estrogen-related receptor β/γ (ERRβ/γ). ERRγ is an orphan nuclear receptor that plays an important role in development and homeostasis and holds potential as a novel therapeutic target in metabolic diseases such as diabetes mellitus, obesity, and cancer. ERRβ is also one of the orphan nuclear receptors critical for many biological processes, such as development. We investigated the in vitro metabolism of DN203368 by conventional and metabolomic approaches using high-resolution mass spectrometry. The compound (100 μM) was incubated with rat and human liver microsomes in the presence of NADPH. In the metabolomic approach, the m/z value and retention time information obtained from the sample and heat-inactivated control group were statistically evaluated using principal component analysis and orthogonal partial least-squares discriminant analysis. Significant features responsible for group separation were then identified using tandem mass spectra. Seven metabolites of DN203368 were identified in rat liver microsomes and the metabolic pathways include hydroxylation (M1-3), N-oxidation (M4), N-deisopropylation (M5), N,N-dealkylation (M6), and oxidation and dehydrogenation (M7). Only five metabolites (M2, M3, and M5-M7) were detected in human liver microsomes. In the conventional approach using extracted ion monitoring for values of mass increase or decrease by known metabolic reactions, only five metabolites (M1-M5) were found in rat liver microsomes, whereas three metabolites (M2, M3, and M5) were found in human liver microsomes. This study revealed that nontargeted metabolomics combined with high-resolution mass spectrometry and multivariate analysis could be a more efficient tool for drug metabolite identification than the conventional approach. These results might also be useful for understanding the pharmacokinetics and metabolism of DN203368 in animals and humans.

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).

scholarly journals Stimulation of lipid peroxidation and hydroxyl-radical generation by the contents of human atherosclerotic lesions

1992 ◽  
Vol 286 (3) ◽  
pp. 901-905 ◽  
Author(s):  
C Smith ◽  
M J Mitchinson ◽  
O I Aruoma ◽  
B Halliwell
Keyword(s):  
Lipid Peroxidation ◽  
Copper Ions ◽  
Liver Microsomes ◽  
Rat Liver Microsomes ◽  
Atherosclerotic Lesions ◽  
Arterial Lesions ◽  
Human Cadavers ◽  
Radical Generation ◽  
Almost All

Lipid peroxidation within human arterial lesions is thought to play an important role in the development of atherosclerosis. Peroxidation can be accelerated by the presence of ‘catalytic’ iron or copper ions. Gruel samples from advanced atherosclerotic lesions in the abdominal aortae of human cadavers were tested for pro-oxidant properties. All samples contained bleomycin-detectable iron and phenanthroline-detectable copper. Almost all gruel samples stimulated peroxidation of rat liver microsomes, and this was usually inhibited by the iron-ion chelator desferrioxamine. Some samples stimulated formation of hydroxyl radicals from H2O2 in the presence of ascorbate, a reaction again inhibited by desferrioxamine. We conclude that the interior of human advanced atherosclerotic lesions is a highly pro-oxidant environment, and that the use of copper or iron ions to promote peroxidation of low-density lipoproteins in vitro may be a valid model for events in the arterial wall.

A comparison of the in vitro metabolism of biphenyl and 4-chlorobiphenyl by rat liver microsomes

1978 ◽  
Vol 56 (10) ◽  
pp. 993-997 ◽  
Author(s):  
C. Wyndham ◽  
S. Safe
Keyword(s):  
Polychlorinated Biphenyl ◽  
Liver Microsomes ◽  
Low Molecular Weight ◽  
Rat Liver Microsomes ◽  
Hepatic Microsomes ◽  
Comparative Metabolism ◽  
Metabolic Products ◽  
Active Substrate ◽  
And Control

The comparative metabolism of the hydrocarbons, biphenyl and 4-chlorobiphenyl, was investigated using two different preparations of rat hepatic microsomes. The assay was designed to account for all the metabolic products which included the ether soluble lipophilic metabolites, low molecular weight conjugates, and macromolecular adducts, and to determine the effects of induction with Aroclor 1254 and 1248, two commercial polychlorinated biphenyl (PCB) preparations. 4-Chlorobiphenyl was the more metabolically active substrate with the induced and control enzymes. In most metabolic fractions biphenyl was less inducible by the PCB's, with the exception of the 2-biphenylol metabolite which was induced ca. 18-fold. Preincubation of the microsomes with carcinogens did not enhance biphenyl 2-hydroxylation. Instead, a general inhibition of metabolic activity was observed for both biphenyl and 4-chlorobiphenyl substrates. Preincubation with phenobarbitone, a noncarcinogen, did not change the microsome-mediated metabolism of biphenyl or 4-chlorobiphenyl. The substitution of a single halogen atom on the biphenyl nucleus altered both the reactivity and pattern of metabolites for these substrates.

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