In vivo cytochrome P450 activity alterations in diabetic nonalcoholic steatohepatitis mice
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Final Accepted Manuscript
Author
Li, HuiClarke, John D.
Dzierlenga, Anika L.
Bear, John
Goedken, Michael J.
Cherrington, Nathan J.
Affiliation
Department of Pharmacology and Toxicology, University of ArizonaStatistical Consulting Lab, Univeristy of Arizona
Issue Date
2017-02Keywords
Cytochrome P450methionine and choline deficient
nonalcoholic steatohepatitis
variable drug
responses
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WileyCitation
In vivo cytochrome P450 activity alterations in diabetic nonalcoholic steatohepatitis mice 2017, 31 (2):e21840 Journal of Biochemical and Molecular ToxicologyRights
© 2016 Wiley Periodicals, Inc.Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
Nonalcoholic steatohepatitis (NASH) has been identified as a source of significant inter individual variation in drug metabolism. A previous ex vivo study demonstrated significant changes in hepatic Cytochrome P450 (CYP) activity in human NASH. This study evaluated the in vivo activities of multiple CYP isoforms simultaneously in prominent diabetic NASH mouse models. The pharmacokinetics of CYP selective substrates: caffeine, losartan, and omeprazole changed significantly in a diabetic NASH mouse model, indicating attenuation of the activity of Cyp1a2 and Cyp2c29, respectively. Decreased mRNA expression of Cyp1a2 and Cyp2c29, as well as an overall decrease in CYP protein expression, was found in the diabetic NASH mice. Overall, these data suggest that the diabetic NASH model only partially recapitulates the human ex vivo CYP alteration pattern. Therefore, in vivo determination of the effects of NASH on CYP activity should be conducted in human, and more appropriate models are required for future drug metabolism studies in NASH.Note
12 month embargo; Version of record online: 6 October 2016ISSN
10956670Version
Final accepted manuscriptSponsors
National Institutes of Health [ES006694, HD062489]; National Institute of Environmental Health Science. Toxicology Training Grant [ES007091]Additional Links
http://doi.wiley.com/10.1002/jbt.21840ae974a485f413a2113503eed53cd6c53
10.1002/jbt.21840