Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Editor

Personal info

View

About

Terms

Javascript disabled

Please enable Javascript support in your browser to use this application.

Instructions on how to enable JavaScript on different browsers can be found here: http://www.google.com/support/bin/answer.py?answer=23852.

[edit this page]

Pickup, K. et al.

Kathryn Pickup, Alex Gavin, Huw B. Jones, Elin Karlsson, Chris Page, Kerry Ratcliffe, Sunil Sarda, Timothy Schulz-Utermoehl, Ian Wilson,

The hepatic reductase null mouse as a model for exploring hepatic conjugation of xenobiotics: application to the metabolism of diclofenac.

The distribution, metabolism, excretion and hepatic effects of diclofenac were investigated following a single oral dose of 10 mg/kg to wild type and hepatic reductase null (HRN) mice. For the HRN strain the bulk of the [(14)C]-diclofenac-related material was excreted in the urine/aqueous cagewash within 12 h of administration (~82%) with only small amounts eliminated via the faeces (~2% in 24 h). Wild type mice excreted the radiolabel more slowly with ca. 52 and 15% of the dose recovered excreted in urine and faeces, respectively, by 24 h post dose. The metabolic profiles of the HRN mice were dominated by acyl conjugation to either taurine or glucuronic acid. Wild type mice produced relatively small amounts of the acyl glucuronide. Whole Body Autoradiography (WBA) of mice sacrificed at 24 h post dose indicated increased retention of radioactivity in the livers of HRN mice compared to wild type mice. Covalent binding studies showed no differences between the two strains. Metabolism of diclofenac in HRN mice involved mainly acyl glucuronide formation and taurine amide conjugation. This mouse model may find utility in understanding the impact of reactive metabolite formation via routes that involve the production of acyl-CoA or acyl glucuronides of acidic drugs.[1]

References

The hepatic reductase null mouse as a model for exploring hepatic conjugation of xenobiotics: application to the metabolism of diclofenac. Pickup, K., Gavin, A., Jones, H.B., Karlsson, E., Page, C., Ratcliffe, K., Sarda, S., Schulz-Utermoehl, T., Wilson, I. Xenobiotica (2012) [Pubmed]

Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenes Open Access Licence Privacy Policy Terms of Use apsburg

The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.