In vivo cytochrome P450 activity alterations in diabetic nonalcoholic steatohepatitis mice

Persistent Link:
http://hdl.handle.net/10150/623536
Title:
In vivo cytochrome P450 activity alterations in diabetic nonalcoholic steatohepatitis mice
Author:
Li, Hui; Clarke, John D.; Dzierlenga, Anika L.; Bear, John; Goedken, Michael J.; Cherrington, Nathan J.
Affiliation:
Department of Pharmacology and Toxicology, University of Arizona; Statistical Consulting Lab, Univeristy of Arizona
Issue Date:
2017-02
Publisher:
Wiley
Citation:
In vivo cytochrome P450 activity alterations in diabetic nonalcoholic steatohepatitis mice 2017, 31 (2):e21840 Journal of Biochemical and Molecular Toxicology
Journal:
Journal of Biochemical and Molecular Toxicology
Rights:
© 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 2016
ISSN:
10956670
DOI:
10.1002/jbt.21840
Keywords:
Cytochrome P450; methionine and choline deficient; nonalcoholic steatohepatitis; variable drug; responses
Version:
Final accepted manuscript
Sponsors:
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.21840

Full metadata record

DC FieldValue Language
dc.contributor.authorLi, Huien
dc.contributor.authorClarke, John D.en
dc.contributor.authorDzierlenga, Anika L.en
dc.contributor.authorBear, Johnen
dc.contributor.authorGoedken, Michael J.en
dc.contributor.authorCherrington, Nathan J.en
dc.date.accessioned2017-05-18T18:20:11Z-
dc.date.available2017-05-18T18:20:11Z-
dc.date.issued2017-02-
dc.identifier.citationIn vivo cytochrome P450 activity alterations in diabetic nonalcoholic steatohepatitis mice 2017, 31 (2):e21840 Journal of Biochemical and Molecular Toxicologyen
dc.identifier.issn10956670-
dc.identifier.doi10.1002/jbt.21840-
dc.identifier.urihttp://hdl.handle.net/10150/623536-
dc.description.abstractNonalcoholic 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.en
dc.description.sponsorshipNational Institutes of Health [ES006694, HD062489]; National Institute of Environmental Health Science. Toxicology Training Grant [ES007091]en
dc.language.isoenen
dc.publisherWileyen
dc.relation.urlhttp://doi.wiley.com/10.1002/jbt.21840en
dc.rights© 2016 Wiley Periodicals, Inc.en
dc.subjectCytochrome P450en
dc.subjectmethionine and choline deficienten
dc.subjectnonalcoholic steatohepatitisen
dc.subjectvariable drugen
dc.subjectresponsesen
dc.titleIn vivo cytochrome P450 activity alterations in diabetic nonalcoholic steatohepatitis miceen
dc.typeArticleen
dc.contributor.departmentDepartment of Pharmacology and Toxicology, University of Arizonaen
dc.contributor.departmentStatistical Consulting Lab, Univeristy of Arizonaen
dc.identifier.journalJournal of Biochemical and Molecular Toxicologyen
dc.description.note12 month embargo; Version of record online: 6 October 2016en
dc.description.collectioninformationThis 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.en
dc.eprint.versionFinal accepted manuscripten
dc.contributor.institutionDepartment of Pharmacology and Toxicology; University of Arizona; Tucson AZ 85721 USA-
dc.contributor.institutionDepartment of Pharmacology and Toxicology; University of Arizona; Tucson AZ 85721 USA-
dc.contributor.institutionDepartment of Pharmacology and Toxicology; University of Arizona; Tucson AZ 85721 USA-
dc.contributor.institutionStatistical Consulting Lab; Univeristy of Arizona; Tucson AZ 85721 USA-
dc.contributor.institutionTranslational Sciences, Research Pathology Services; Rutgers University; New Brunswick NJ 08854 USA-
dc.contributor.institutionDepartment of Pharmacology and Toxicology; University of Arizona; Tucson AZ 85721 USA-
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