The Disruption of Hepatic Cytochrome P450 Reductase Alters Mouse Lipid Metabolism

2007 ◽  
Vol 6 (10) ◽  
pp. 3976-3984 ◽  
Author(s):  
David M. Mutch ◽  
Bernward Klocke ◽  
Peter Morrison ◽  
Carol A. Murray ◽  
Colin J. Henderson ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Lipid Metabolism ◽  
Cytochrome P450 Reductase ◽  
P450 Reductase ◽  
Hepatic Cytochrome

scholarly journals Improved hepatic physiology in hepatic cytochrome P450 reductase null (HRN™) mice dosed orally with fenclozic acid

2017 ◽  
Vol 6 (1) ◽  
pp. 81-88 ◽  
Author(s):  
James A. Akingbasote ◽  
Alison J. Foster ◽  
Huw B. Jones ◽  
Rhiannon David ◽  
Nigel J. Gooderham ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Toxicity ◽  
Cytochrome P450 Reductase ◽  
Hepatic Drug ◽  
P450 Reductase ◽  
Liver Histopathology ◽  
Drug Biotransformation ◽  
Fenclozic Acid ◽  
Hepatic Cytochrome

HRN™ mice are valuable for P450-related hepatic drug biotransformation assessment, but not drug toxicity due to underlying liver histopathology.

Hepatic effects of repeated oral administration of diclofenac to hepatic cytochrome P450 reductase null (HRN™) and wild-type mice

2015 ◽  
Vol 90 (4) ◽  
pp. 853-862 ◽  
Author(s):  
James A. Akingbasote ◽  
Alison J. Foster ◽  
Ian Wilson ◽  
Sunil Sarda ◽  
Huw B. Jones ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Oral Administration ◽  
Cytochrome P450 Reductase ◽  
Wild Type ◽  
P450 Reductase ◽  
Hepatic Cytochrome

scholarly journals Relationship between hepatic phenotype and changes in gene expression in cytochrome P450 reductase (POR) null mice

2005 ◽  
Vol 388 (3) ◽  
pp. 857-867 ◽  
Author(s):  
Xiu Jun WANG ◽  
Mark CHAMBERLAIN ◽  
Olga VASSIEVA ◽  
Colin J. HENDERSON ◽  
C. Roland WOLF
Keyword(s):  
Cytochrome P450 ◽  
Bile Acid ◽  
Serum Testosterone ◽  
Cytochrome P450 Reductase ◽  
Endogenous Factors ◽  
Key Enzymes ◽  
P450 Reductase ◽  
Cytochrome P450 Activity ◽  
Steroid Dehydrogenase ◽  
Hepatic Cytochrome

Cytochrome P450 reductase is the unique electron donor for microsomal cytochrome P450s; these enzymes play a major role in the metabolism of endogenous and xenobiotic compounds. In mice with a liver-specific deletion of cytochrome P450 reductase, hepatic cytochrome P450 activity is ablated, with consequent changes in bile acid and lipid homoeostasis. In order to gain insights into the metabolic changes resulting from this phenotype, we have analysed changes in hepatic mRNA expression using microarray analysis and real-time PCR. In parallel with the perturbations in bile acid levels, changes in the expression of key enzymes involved in cholesterol and lipid homoeostasis were observed in hepatic cytochrome P450 reductase null mice. This was characterized by a reduced expression of Cyp7b1, and elevation of Cyp7a1 and Cyp8b1 expression. The levels of mRNAs for other cytochrome P450 genes, including Cyp2b10, Cyp2c29, Cyp3a11 and Cyp3a16, were increased, demonstrating that endogenous factors play a role in regulating the expression of these proteins and that the increases are due, at least in part, to altered levels of transcripts. In addition, levels of mRNAs encoding genes involved in glycolysis and lipid transport were also increased; the latter may provide an explanation for the increased hepatic lipid content observed in the hepatic null mice. Serum testosterone and oestradiol levels were lowered, accompanied by significantly decreased expression of Hsd3b2 (3β-hydroxy-Δ5-steroid dehydrogenase-2), Hsd3b5 (3β-hydroxy-Δ5-steroid dehydrogenase-5) and Hsd11b1 (11β-hydroxysteroid dehydrogenase type 1), key enzymes in steroid hormone metabolism. These microarray data provide important insights into the control of metabolic pathways by the cytochrome system.

scholarly journals Inactivation of the Hepatic Cytochrome P450 System by Conditional Deletion of Hepatic Cytochrome P450 Reductase

2003 ◽  
Vol 278 (15) ◽  
pp. 13480-13486 ◽  
Author(s):  
Colin J. Henderson ◽  
Diana M. E. Otto ◽  
Dianne Carrie ◽  
Mark A. Magnuson ◽  
Aileen W. McLaren ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 Reductase ◽  
Cytochrome P450 System ◽  
P450 Reductase ◽  
Conditional Deletion ◽  
Hepatic Cytochrome
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