scholarly journals Global Proteomic Analysis of Human Liver Microsomes: Rapid Characterization and Quantification of Hepatic Drug-Metabolizing Enzymes

2017 ◽  
Vol 45 (6) ◽  
pp. 666-675 ◽  
Author(s):  
Brahim Achour ◽  
Hajar Al Feteisi ◽  
Francesco Lanucara ◽  
Amin Rostami-Hodjegan ◽  
Jill Barber
Keyword(s):  
Proteomic Analysis ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Drug Metabolizing Enzymes ◽  
Metabolizing Enzymes ◽  
Hepatic Drug ◽  
Rapid Characterization

Use of SWATH-MS to relatively quantify the expression of hepatic drug metabolizing enzymes in human liver microsomes using a label-free approach

2018 ◽  
Vol 33 (1) ◽  
pp. S57-S58
Author(s):  
Rohitash Jamwal ◽  
Benjamin J. Barlock ◽  
Sravani Adusumalli ◽  
Ken Ogasawara ◽  
Brigitte L. Simons ◽  
...  
Keyword(s):  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Drug Metabolizing Enzymes ◽  
Label Free ◽  
Metabolizing Enzymes ◽  
Hepatic Drug

Metabolism of Chamaechromone In Vitro with Human Liver Microsomes and Recombinant Human Drug-Metabolizing Enzymes

Planta Medica ◽  
2014 ◽  
Vol 80 (06) ◽  
pp. 493-497 ◽  
Author(s):  
Yan Lou ◽  
Haihong Hu ◽  
Yunqing Qiu ◽  
Jinqi Zheng ◽  
Linrun Wang ◽  
...  
Keyword(s):  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Drug Metabolizing Enzymes ◽  
Metabolizing Enzymes

scholarly journals Dataset from proteomic analysis of rat, mouse, and human liver microsomes and S9 fractions

Data in Brief ◽  
2015 ◽  
Vol 3 ◽  
pp. 95-98 ◽  
Author(s):  
Makan Golizeh ◽  
Christina Schneider ◽  
Leanne B. Ohlund ◽  
Lekha Sleno
Keyword(s):  
Proteomic Analysis ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes

A new calibration curve calculation method for absolute quantification of drug metabolizing enzymes in human liver microsomes by stable isotope dilution mass spectrometry

2015 ◽  
Vol 7 (14) ◽  
pp. 5934-5941 ◽  
Author(s):  
Huanhuan Wang ◽  
Haifeng Zhang ◽  
Jiabin Li ◽  
Junying Wei ◽  
Rui Zhai ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Stable Isotope ◽  
Calibration Curve ◽  
Human Liver ◽  
Isotope Dilution Mass Spectrometry ◽  
Liver Microsomes ◽  
Absolute Quantification ◽  
Drug Metabolizing Enzymes ◽  
Metabolizing Enzymes ◽  
Stable Isotope Dilution

A new calibration curve calculation method in stable isotope dilution mass spectrometry for absolute quantification of drug metabolizing enzymes in human liver microsomes.

scholarly journals Strong and Selective Inhibitory Effects of the Biflavonoid Selamariscina A against CYP2C8 and CYP2C9 Enzyme Activities in Human Liver Microsomes

Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 343
Author(s):  
So-Young Park ◽  
Phi-Hung Nguyen ◽  
Gahyun Kim ◽  
Su-Nyeong Jang ◽  
Ga-Hyun Lee ◽  
...  
Keyword(s):  
Enzyme Activities ◽  
Human Liver ◽  
Liver Microsomes ◽  
Plant Secondary Metabolites ◽  
Human Liver Microsomes ◽  
Inhibitory Effects ◽  
Metabolizing Enzymes ◽  
Anti Cancer ◽  
Liquid Chromatography Tandem Mass ◽  
Inhibitory Potential

Like flavonoids, biflavonoids, dimeric flavonoids, and polyphenolic plant secondary metabolites have antioxidant, antibacterial, antiviral, anti-inflammatory, and anti-cancer properties. However, there is limited data on their effects on cytochrome P450 (P450) and uridine 5′-diphosphoglucuronosyl transferase (UGT) enzyme activities. In this study we evaluate the inhibitory potential of five biflavonoids against nine P450 activities (P450s1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A) in human liver microsomes (HLMs) using cocktail incubation and liquid chromatography-tandem mass spectrometry (LC–MS/MS). The most strongly inhibited P450 activity was CYP2C8-mediated amodiaquine N-dealkylation with IC50 ranges of 0.019~0.123 μM. In addition, the biflavonoids—selamariscina A, amentoflavone, robustaflavone, cupressuflavone, and taiwaniaflavone—noncompetitively inhibited CYP2C8 activity with respective Ki values of 0.018, 0.083, 0.084, 0.103, and 0.142 μM. As selamariscina A showed the strongest effects, we then evaluated it against six UGT isoforms, where it showed weaker inhibition (UGTs1A1, 1A3, 1A4, 1A6, 1A9, and 2B7, IC50 > 1.7 μM). Returning to the P450 activities, selamariscina A inhibited CYP2C9-mediated diclofenac hydroxylation and tolbutamide hydroxylation with respective Ki values of 0.032 and 0.065 μM in a competitive and noncompetitive manner. However, it only weakly inhibited CYP1A2, CYP2B6, and CYP3A with respective Ki values of 3.1, 7.9, and 4.5 μM. We conclude that selamariscina A has selective and strong inhibitory effects on the CYP2C8 and CYP2C9 isoforms. This information might be useful in predicting herb-drug interaction potential between biflavonoids and co-administered drugs mainly metabolized by CYP2C8 and CYP2C9. In addition, selamariscina A might be used as a strong CYP2C8 and CYP2C9 inhibitor in P450 reaction-phenotyping studies to identify drug-metabolizing enzymes responsible for the metabolism of new chemicals.

scholarly journals Inhibitory and Inductive Effects of Opuntia ficus indica Extract and Its Flavonoid Constituents on Cytochrome P450s and UDP-Glucuronosyltransferases

2018 ◽  
Vol 19 (11) ◽  
pp. 3400 ◽  
Author(s):  
Hyesoo Jeong ◽  
Soolin Kim ◽  
Mi-yeon Kim ◽  
Jimin Lee ◽  
Byoung An ◽  
...  
Keyword(s):  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Uridine Diphosphate ◽  
Metabolizing Enzymes ◽  
Opuntia Ficus Indica ◽  
Ovx Rats ◽  
Human Hepatocarcinoma Cell Line ◽  
Menopausal Women ◽  
Inductive Effects

Opuntia ficus indica (OFI) is grown abundantly in arid areas and its fruits are regarded as an important food and nutrient source owing to the presence of flavonoids, minerals, and proteins. The previous report that OFI exerts phytoestrogenic activity makes it plausible for OFI-containing supplements to be used as alternative estrogen replacement therapy. In the case of polypharmacy with the consumption of OFI-containing botanicals in post- or peri-menopausal women, it is critical to determine the potential drug-OFI interaction due to the modulation of drug metabolism. In the present study, the modulating effects on the hepatic drug metabolizing enzymes (DMEs) by OFI and its flavonoid constituents (kaempferol, quercetin, isorhamnetin, and their glycosidic forms) were investigated using the liver microsomal fractions prepared from ovariectomized (OVX) rats, human liver microsomes, and human hepatocarcinoma cell line (HepG2). As a result, the oral administration of extracts of OFI (OFIE) in OVX rats induced hepatic CYP2B1, CYP3A1, and UGT2B1. OFIE, hydrolyzed (hdl) OFIE, and several flavonols induced the transcriptional activities of both CYP2B6 and CYP3A4 genes in HepG2 cells. Finally, OFIE did not inhibit activities of cytochrome P450 (CYPs) or uridine diphosphate (UDP)-glucuronosyltransferases (UGTs), whereas hdl OFIE or flavonol treatment inhibited CYP1A2 and CYP3A1/3A4 in rat and human liver microsomes. Our data demonstrate that OFIE may induce or inhibit certain types of DMEs and indicate that drug-OFI interaction may occur when the substrate or inhibitor drugs of specific CYPs or UGTs are taken concomitantly with OFI-containing products.

Deactivation of anti-cancer drug letrozole to a carbinol metabolite by polymorphic cytochrome P450 2A6 in human liver microsomes

Xenobiotica ◽  
2009 ◽  
Vol 00 (00) ◽  
pp. 090901052053001-8
Author(s):  
K. Murai ◽  
H. Yamazaki ◽  
K. Nakagawa ◽  
R. Kawai ◽  
T. Kamataki
Keyword(s):  
Cytochrome P450 ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Cancer Drug ◽  
Anti Cancer ◽  
Cytochrome P450 2A6

Selegiline Metabolism and Cytochrome P450 Enzymes:In vitro Study in Human Liver Microsomes*

2000 ◽  
Vol 86 (5) ◽  
pp. 215-221 ◽  
Author(s):  
Paivi Taavitsainen ◽  
Markku Anttila ◽  
Leena Nyman ◽  
Hari Karnani ◽  
Jarmo S. Salonen ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Vitro Study
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