Molecular and macromolecular alterations of recombinant adenoviral vectors do not resolve changes in hepatic drug metabolism during infection

In this report we test the hypothesis that long-term virus-induced alterations in CYP occur from changes initiated by the virus that may not be related to the immune response. Enzyme activity, protein expression and mRNA of CYP3A2, a correlate of human CYP3A4, and CYP2C11, responsive to inflammatory...

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Bibliographic Details
Published in:Virology journal 2008-09, Vol.5 (1), p.111-111, Article 111
Main Authors: Callahan, Shellie M, Wonganan, Piyanuch, Croyle, Maria A
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Adenoviridae - metabolism
Adenoviridae Infections - enzymology
Adenoviridae Infections - genetics
Adenoviridae Infections - virology
Adenovirus
Alanine Transaminase - blood
Animals
Aryl Hydrocarbon Hydroxylases - genetics
Aryl Hydrocarbon Hydroxylases - metabolism
Cell Line
Cells, Cultured
Cytochrome P-450 CYP3A
Cytochrome P450 Family 2
Drug metabolism
Gene Expression
Genetic aspects
Genetic Vectors - genetics
Genetic Vectors - metabolism
Hepatocytes - enzymology
Hepatocytes - virology
Humans
Liver - enzymology
Liver - virology
Male
Membrane Proteins - genetics
Membrane Proteins - metabolism
Rats
Rats, Sprague-Dawley
Steroid 16-alpha-Hydroxylase - genetics
Steroid 16-alpha-Hydroxylase - metabolism
Virus diseases
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Summary:In this report we test the hypothesis that long-term virus-induced alterations in CYP occur from changes initiated by the virus that may not be related to the immune response. Enzyme activity, protein expression and mRNA of CYP3A2, a correlate of human CYP3A4, and CYP2C11, responsive to inflammatory mediators, were assessed 0.25, 1, 4, and 14 days after administration of several different recombinant adenoviruses at a dose of 5.7 x 1012 virus particles (vp)/kg to male Sprague Dawley rats. Wild type adenovirus, containing all viral genes, suppressed CYP3A2 and 2C11 activity by 37% and 39%, respectively within six hours. Levels fell to 67% (CYP3A2) and 79% (CYP2C11) of control by 14 days (p
ISSN:1743-422X
1743-422X
DOI:10.1186/1743-422X-5-111