Inhibition of Cytochrome P450 2C8-mediated Drug Metabolism by the Flavonoid Diosmetin

2011 ◽  
Vol 26 (6) ◽  
pp. 559-568 ◽  
Author(s):  
Luigi Quintieri ◽  
Pietro Palatini ◽  
Stefano Moro ◽  
Maura Floreani
2013 ◽  
Vol 13 (18) ◽  
pp. 2241-2253 ◽  
Author(s):  
Xiaoping Lv ◽  
Fangfang Zhong ◽  
Xiangshi Tan

2015 ◽  
Vol 68 (1) ◽  
pp. 168-241 ◽  
Author(s):  
Janne T. Backman ◽  
Anne M. Filppula ◽  
Mikko Niemi ◽  
Pertti J. Neuvonen

2019 ◽  
Vol 18 (23) ◽  
pp. 2042-2055 ◽  
Author(s):  
Neeraj Kumar ◽  
Heerak Chugh ◽  
Damini Sood ◽  
Snigdha Singh ◽  
Aarushi Singh ◽  
...  

Heme is central to functions of many biologically important enzymes (hemoproteins). It is an assembly of four porphyrin rings joined through methylene bridges with a central Fe (II). Heme is present in all cells, and its synthesis and degradation balance its amount in the cell. The deregulations of heme networks and incorporation in hemoproteins lead to pathogenic state. This article addresses the detailed structure, biosynthesis, degradation, and transportation associated afflictions to heme. The article is followed by its roles in various diseased conditions where it is produced mainly as the cause of increased hemolysis. It manifests the symptoms in diseases as it is a pro-oxidant, pro-inflammatory and pro-hemolytic agent. We have also discussed the genetic defects that tampered with the biosynthesis, degradation, and transportation of heme. In addition, a brief about the largest hemoprotein group of enzymes- Cytochrome P450 (CYP450) has been discussed with its roles in drug metabolism.


2021 ◽  
Author(s):  
Jakob Mühlbacher ◽  
Christian Schörgenhofer ◽  
Konstantin Doberer ◽  
Michael Dürr ◽  
Klemens Budde ◽  
...  

Author(s):  
Lawrence Howell ◽  
Rosalind E. Jenkins ◽  
Stephen Lynch ◽  
Carrie Duckworth ◽  
B. Kevin Park ◽  
...  

AbstractHepatic organoids are a recent innovation in in vitro modeling. Initial studies suggest that organoids better recapitulate the liver phenotype in vitro compared to pre-existing proliferative cell models. However, their potential for drug metabolism and detoxification remains poorly characterized, and their global proteome has yet to be compared to their tissue of origin. This analysis is urgently needed to determine what gain-of-function this new model may represent for modeling the physiological and toxicological response of the liver to xenobiotics. Global proteomic profiling of undifferentiated and differentiated hepatic murine organoids and donor-matched livers was, therefore, performed to assess both their similarity to liver tissue, and the expression of drug-metabolizing enzymes and transporters. This analysis quantified 4405 proteins across all sample types. Data are available via ProteomeXchange (PXD017986). Differentiation of organoids significantly increased the expression of multiple cytochrome P450, phase II enzymes, liver biomarkers and hepatic transporters. While the final phenotype of differentiated organoids is distinct from liver tissue, the organoids contain multiple drug metabolizing and transporter proteins necessary for liver function and drug metabolism, such as cytochrome P450 3A, glutathione-S-transferase alpha and multidrug resistance protein 1A. Indeed, the differentiated organoids were shown to exhibit increased sensitivity to midazolam (10–1000 µM) and irinotecan (1–100 µM), when compared to the undifferentiated organoids. The predicted reduced activity of HNF4A and a resulting dysregulation of RNA polymerase II may explain the partial differentiation of the organoids. Although further experimentation, optimization and characterization is needed relative to pre-existing models to fully contextualize their use as an in vitro model of drug-induced liver injury, hepatic organoids represent an attractive novel model of the response of the liver to xenobiotics. The current study also highlights the utility of global proteomic analyses for rapid and accurate evaluation of organoid-based test systems.


1981 ◽  
Vol 30 (11) ◽  
pp. 1223-1225 ◽  
Author(s):  
R.G. Turcan ◽  
P.P. Tamburini ◽  
G.G. Gibson ◽  
D.V. Parke ◽  
A.M. Symons

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