Metabolism of clozapine by rat brain: the role of flavin-containing monooxygenase (FMO) and cytochrome P450 enzymes

2000 ◽  
Vol 25 (2) ◽  
pp. 109-114 ◽  
Author(s):  
J. Fang
2008 ◽  
Vol 36 (8) ◽  
pp. 1637-1649 ◽  
Author(s):  
Robin E. Pearce ◽  
Wei Lu ◽  
YongQiang Wang ◽  
Jack P. Uetrecht ◽  
Maria Almira Correia ◽  
...  

2018 ◽  
Vol 115 ◽  
pp. 375-384 ◽  
Author(s):  
Young Jae Choi ◽  
Ji-Yoon Lee ◽  
Chang Seon Ryu ◽  
Yong Ha Chi ◽  
Soo Heui Paik ◽  
...  

2019 ◽  
Vol 172 (1) ◽  
pp. 123-131
Author(s):  
Matthew Hartog ◽  
Qing-Yu Zhang ◽  
Xinxin Ding

Abstract Many constituents of tobacco smoke (TS) require bioactivation to exert toxic effects; however, few studies have examined the role of bioactivation enzymes in the adverse effects of TS exposure. This knowledge gap is a major source of uncertainty for risk assessment and chemoprevention efforts. Our aim is to test the hypothesis that cytochrome P450 (P450) enzyme-mediated bioactivation is essential to the development of TS exposure-induced lung toxicity, by determining the contributions of P450 enzymes in the mouse Cyp2abfgs gene subfamilies to environmental tobacco smoke (ETS)-induced lung inflammation. Adult female wildtype (WT) and Cyp2abfgs-null mice (both on C57BL/6J background) were exposed to filtered air or ETS, intermittently, for 1 or 2 weeks. Lung inflammation was assessed by quantification of inflammatory cells, cytokines, chemokines, and proteins in bronchoalveolar lavage fluid (BALF) and histopathological analysis. Glutathione (GSH) conjugates of 2 ETS constituents, naphthalene (NA), and 3-methylindole (3MI), were measured in mice exposed to ETS for 4 h. Persistent macrophagic and neutrophilic lung inflammation was observed in ETS-exposed WT mice; the extent of which was significantly reduced in ETS-exposed Cyp2abfgs-null mice. Levels of proinflammatory cytokines and chemokines, along with the total protein concentration, were increased in cell-free BALF from ETS-exposed WT mice, but not Cyp2abfgs-null mice. Additionally, GSH conjugates of NA and 3MI were detected in the lungs of WT, but not Cyp2abfgs-null, mice following ETS exposure. These results provide the first in vivo evidence that the mouse Cyp2abfgs gene cluster plays an important role in ETS-induced lung inflammation.


Xenobiotica ◽  
2004 ◽  
Vol 34 (4) ◽  
pp. 335-344 ◽  
Author(s):  
S. A. Benetton ◽  
V. M. Borges ◽  
T. K. H. Chang ◽  
K. M. Mcerlane

2004 ◽  
Vol 5 (6) ◽  
pp. 573-579 ◽  
Author(s):  
R. Berecz ◽  
P. Dorado ◽  
A. Rubia ◽  
M. Caceres ◽  
I. Degrell ◽  
...  

2013 ◽  
Vol 23 (5) ◽  
pp. 346-351 ◽  
Author(s):  
Daria Kraus ◽  
Dennis Rokitta ◽  
Uwe Fuhr ◽  
Dorota Tomalik-Scharte

2009 ◽  
Vol 10 (2) ◽  
pp. 164-178 ◽  
Author(s):  
Beshay Zordoky ◽  
Ayman El-Kadi

2020 ◽  
Author(s):  
Chenyang Zhang ◽  
Haoqing Shao ◽  
Dandan Li ◽  
Nenqun Xiao ◽  
Zhoujin Tan

Abstract Background: Although reports have provided evidence that diarrhea caused by Folium sennae can result in intestinal microbiota diversity disorder, the intestinal bacterial characteristic and specific mechanism are still unknown. The objective of our study was to investigate the mechanism of diarrhea caused by Folium sennae, which was associated with intestinal bacterial characteristic reshaping and metabolic abnormality. Results: For the intervention of Folium sennae extracts, Chao1 index and Shannon index were statistical decreased. The Beta diversity clusters of mice interfered by Folium sennae extracts were distinctly separated from control group. Combining PPI network analysis, cytochrome P450 enzymes metabolism was the main signaling pathway of diarrhea caused by Folium sennae. Moreover, 10 bacterial flora communities had statistical significant difference with Folium sennae intervention: the abundance of Paraprevotella, Streptococcus, Epulopiscium, Sutterella and Mycoplasma increased significantly; and the abundance of Adlercreutzia, Lactobacillus, Dehalobacterium, Dorea and Oscillospira reduced significantly. 7 of the 10 intestinal microbiota communities were related to the synthesis of tryptophan derivatives, which affected the transformation of aminotryptophan into L-tryptophan, leading to abnormal tryptophan metabolism in the host. Conclusions: Folium sennae targeted cytochrome P450 3A4 to alter intestinal bacterial characteristic and intervene the tryptophan metabolism of intestinal microbiota, such as Streptococcus, Sutterella and Dorea, which could be the intestinal microecological mechanism of diarrhea caused by Folium sennae extracts.


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