scholarly journals Anti‐interleukin‐6 antibody clazakizumab in late antibody‐mediated kidney transplant rejection: effect on cytochrome P450 drug metabolism

2021 ◽  
Author(s):  
Jakob Mühlbacher ◽  
Christian Schörgenhofer ◽  
Konstantin Doberer ◽  
Michael Dürr ◽  
Klemens Budde ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Metabolism ◽  
Kidney Transplant ◽  
Interleukin 6 ◽  
Transplant Rejection

Biology of Heme: Drug Interactions and Adverse Drug Reactions with CYP450

2019 ◽  
Vol 18 (23) ◽  
pp. 2042-2055 ◽  
Author(s):  
Neeraj Kumar ◽  
Heerak Chugh ◽  
Damini Sood ◽  
Snigdha Singh ◽  
Aarushi Singh ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Metabolism ◽  
Drug Interactions ◽  
Adverse Drug Reactions ◽  
Genetic Defects ◽  
Drug Reactions ◽  
Detailed Structure ◽  
Synthesis And Degradation ◽  
Porphyrin Rings

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.

scholarly journals Proteomic profiling of murine biliary-derived hepatic organoids and their capacity for drug disposition, bioactivation and detoxification

2021 ◽  
Author(s):  
Lawrence Howell ◽  
Rosalind E. Jenkins ◽  
Stephen Lynch ◽  
Carrie Duckworth ◽  
B. Kevin Park ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Metabolism ◽  
Rna Polymerase Ii ◽  
Liver Tissue ◽  
Drug Disposition ◽  
Multiple Drug ◽  
Proteomic Profiling ◽  
Cytochrome P450 3A ◽  
Drug Induced

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.

INDIUM-111 LABELLED PLATELETS IN CHRONIC KIDNEY TRANSPLANT REJECTION

The Lancet ◽  
1980 ◽  
Vol 316 (8187) ◽  
pp. 213-214 ◽  
Author(s):  
CH. Leithner ◽  
H. Sinzinger ◽  
P. Angelberger ◽  
G. Syre
Keyword(s):  
Kidney Transplant ◽  
Transplant Rejection ◽  
Indium 111

Drug metabolism, cytochrome P450 spin state, and phospholipid changes during pregnancy in the rat

1981 ◽  
Vol 30 (11) ◽  
pp. 1223-1225 ◽  
Author(s):  
R.G. Turcan ◽  
P.P. Tamburini ◽  
G.G. Gibson ◽  
D.V. Parke ◽  
A.M. Symons
Keyword(s):  
Cytochrome P450 ◽  
Drug Metabolism ◽  
Spin State

Differential diagnosis of kidney transplant rejection and cyclosporin/tacrolimus nephropathy using urine cytology

2002 ◽  
Vol 16 ◽  
pp. 40-44 ◽  
Author(s):  
Masahiro Kyo ◽  
Yasuji Ichikawa ◽  
Kiyohide Toki ◽  
Kennichi Nishimura ◽  
Takanobu Fukunishi ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Kidney Transplant ◽  
Transplant Rejection ◽  
Urine Cytology
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