Mechanism-Based Inhibition of Human Cytochromes P450: In Vitro Kinetics and In Vitro–In Vivo Correlations

2019 ◽  
pp. 515-544
Author(s):  
Xin Zhang ◽  
David R. Jones ◽  
Stephen D. Hall
Keyword(s):  
Cytochromes P450 ◽  
In Vitro Kinetics

Monepantel induces hepatic cytochromes p450 in sheep in vitro and in vivo

2015 ◽  
Vol 227 ◽  
pp. 63-68 ◽  
Author(s):  
Lucie Stuchlíková ◽  
Petra Matoušková ◽  
Hana Bártíková ◽  
Ivan Vokřál ◽  
Jiří Lamka ◽  
...  
Keyword(s):  
Cytochromes P450

scholarly journals Molecular Docking and Preclinical Study of Five-MemberedS,S-Palladaheterocycle as Hepatoprotective Agent

2019 ◽  
Vol 9 (4) ◽  
pp. 674-684 ◽  
Author(s):  
Nail Salavatovich Akhmadiev ◽  
Albina Midkhatovna Galimova ◽  
Vnira Rakhimovna Akhmetova ◽  
Veronika Radievna Khairullina ◽  
Rozaliia Akramovna Galimova ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Survival Data ◽  
Active Sites ◽  
Cytochromes P450 ◽  
Hepatoprotective Activity ◽  
Preclinical Study ◽  
Therapeutic Effects ◽  
Preclinical Trials

Purpose: In order to investigate mechanisms underlying the hepatoprotective action of S,Spalladaheterocycle,inhibition of cytochromes P450 has been modeled by molecular dockingof four palladaheterocycle stereoisomers to the active sites of an enzymatic oxidase system. Toobtain a deeper insight into biochemical aspects providing a basis for the therapeutic effects offive-membered palladacycles (as mixture of stereoisomers), a number of preclinical trials hasbeen conductedMethods: 2D and 3D structures of palladaheterocycle stereoisomers were obtained viaconverting into SDF files by means of software MarvinSketch. Binding of palladaheterocycle atthe active sites of cytochromes P450 2E1 and P450 2C9 has been studied by molecular dockingusing LeadIT 2.3.2. Hepatoprotective activity of palladaheterocycle at 2.5, 25 and 250 mg/kgdoses has been studied based on a model of acute intoxication by CCl4 using in vivo methods.Results: By molecular docking it was identify amino acid fragments responsible for bindingwith palladacyclic isomers. The tested compound is comparable, in terms of its activity tothe hepatoprotective drug SAM according to the in vivo and in vitro experiments such asanimal survival data, the efficiency of correction of the cytolytic syndrome, the liver excretoryfunction, carbohydrate, protein and lipid metabolism, and the correction efficiency of the liverantitoxic function (the latter has been determined based on the results of a hexobarbital controlexperiment).Conclusion: Taking into account results obtained in vivo, in vitro and in silico, it can be concludedthat the five-membered S,S-palladaheterocycle effectively protect the liver against acute damagecaused by CCl4, via activation of catalase and glucuronyltransferase, as well as via inhibition ofthe oxidative stress enzymes.<br />

scholarly journals Biocompatibility studies of fluorescent diamond particles-(NV)∼800nm (part V): in vitro kinetics and in vivo localization in rat liver following long-term exposure

2019 ◽  
Vol Volume 14 ◽  
pp. 6451-6464 ◽  
Author(s):  
Jonathan A Gerstenhaber ◽  
Cezary Marcinkiewicz ◽  
Frank C Barone ◽  
Mark Sternberg ◽  
Michael R D’Andrea ◽  
...  
Keyword(s):  
Rat Liver ◽  
Diamond Particles ◽  
In Vitro Kinetics

P08-15 In vitro kinetics and quantitative in vitro-in vivo extrapolation of nephrotoxicants

2018 ◽  
Vol 295 ◽  
pp. S137
Author(s):  
N. Kramer ◽  
F. Taverne ◽  
A. Mally ◽  
S. Jarzina ◽  
B. Birk ◽  
...  
Keyword(s):  
In Vitro Kinetics ◽  
In Vivo Extrapolation

Reconciling in vivo and in vitro kinetics of the polymorphic transformation in zirconia-toughened alumina for hip joints: I. Phenomenology

2017 ◽  
Vol 72 ◽  
pp. 252-258 ◽  
Author(s):  
B. Sonny Bal ◽  
Wenliang Zhu ◽  
Matteo Zanocco ◽  
Elia Marin ◽  
Nobuhiko Sugano ◽  
...  
Keyword(s):  
Polymorphic Transformation ◽  
Hip Joints ◽  
Kinetics Of ◽  
In Vitro Kinetics ◽  
Zirconia Toughened Alumina

scholarly journals In Vivo and in Vitro Kinetics of Metal Transfer by the Klebsiella aerogenes Urease Nickel Metallochaperone, UreE

2000 ◽  
Vol 275 (15) ◽  
pp. 10731-10737 ◽  
Author(s):  
Gerard J. Colpas ◽  
Robert P. Hausinger
Keyword(s):  
Metal Transfer ◽  
Klebsiella Aerogenes ◽  
Kinetics Of ◽  
In Vitro Kinetics

Lack of mechanism-based inactivation of rat hepatic microsomal cytochromes P450 by doxorubicin

1999 ◽  
Vol 77 (8) ◽  
pp. 589-597 ◽  
Author(s):  
Johnny Di Re ◽  
Chunja Lee ◽  
David S Riddick
Keyword(s):  
Lipid Peroxidation ◽  
Cytochrome P450 ◽  
Reductase Activity ◽  
Cytochromes P450 ◽  
Microsomal Protein ◽  
Positive Control ◽  
Male Rats ◽  
Protein Levels

Administration of the antineoplastic doxorubicin to rodents causes depression of hepatic cytochrome P450 (CYP) dependent biotransformation, an effect that has been partially attributed to the ability of doxorubicin to stimulate microsomal lipid peroxidation. Since doxorubicin can be bioactivated by the CYP/NADPH-CYP reductase system to products that bind covalently to microsomal protein, we hypothesized that doxorubicin functions as a mechanism-based inactivator of hepatic microsomal CYPs and (or) NADPH-CYP reductase under conditions in which doxorubicin-stimulated NADPH-dependent lipid peroxidation is minimized. In vitro studies were conducted with hepatic microsomes isolated from untreated and phenobarbital-treated male rats. Unlike the positive control carbon tetrachloride, doxorubicin (10 µM) did not stimulate NADPH-dependent lipid peroxidation in microsomal incubations containing EDTA (1.5 mM). Doxorubicin did not cause NADPH-dependent loss of microsomal CYP, heme, or steroid hydroxylation activities selective for CYP2A, CYP2B, CYP2C11, and CYP3A. The positive control 1-aminobenzotriazole caused marked NADPH-dependent decreases in all of these parameters. Neither doxorubicin nor 1-aminobenzotriazole caused NADPH-dependent loss of NADPH-CYP reductase activity, and neither compound altered the immunoreactive protein levels of CYP2B, CYP2C11, CYP3A, and NADPH-CYP reductase. These results indicate that a pharmacologically relevant concentration of doxorubicin does not cause direct mechanism-based inactivation of hepatic microsomal CYPs or NADPH-CYP reductase, suggesting that the ability of doxorubicin to depress hepatic CYP-mediated biotransformation in vivo is due to lipid peroxidation mediated heme destruction, altered heme metabolism, and (or) decreased expression of selected CYP enzymes.Key words: doxorubicin, cytochrome P450, mechanism-based inactivation, lipid peroxidation.

Reconciling in vivo and in vitro kinetics of the polymorphic transformation in zirconia-toughened alumina for hip joints: III. Molecular scale mechanisms

2017 ◽  
Vol 71 ◽  
pp. 552-557 ◽  
Author(s):  
Giuseppe Pezzotti ◽  
B. Sonny Bal ◽  
Matteo Zanocco ◽  
Elia Marin ◽  
Nobuhiko Sugano ◽  
...  
Keyword(s):  
Polymorphic Transformation ◽  
Hip Joints ◽  
Molecular Scale ◽  
Kinetics Of ◽  
In Vitro Kinetics ◽  
Zirconia Toughened Alumina

In vivo dissociation kinetics of [3H]quinuclidinyl benzilate: relationship to muscarinic receptor concentration and in vitro kinetics

1991 ◽  
Vol 553 (1) ◽  
pp. 110-116 ◽  
Author(s):  
Raymond E. Gibson ◽  
Barry R. Zeeberg ◽  
John M. Melograna ◽  
Tessica F. Wang ◽  
Jennifer Ruch ◽  
...  
Keyword(s):  
Muscarinic Receptor ◽  
Dissociation Kinetics ◽  
Receptor Concentration ◽  
Kinetics Of ◽  
In Vitro Kinetics ◽  
Quinuclidinyl Benzilate
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