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dc.contributor.authorRoberts, MS
dc.contributor.authorLiu, X
dc.contributor.authorZou, Y
dc.contributor.authorSiebert, GA
dc.contributor.authorChang, P
dc.contributor.authorWhitehouse, MW
dc.contributor.authorFletcher, L
dc.contributor.authorCrawford, DHG
dc.date.accessioned2017-05-03T14:19:50Z
dc.date.available2017-05-03T14:19:50Z
dc.date.issued2011
dc.date.modified2012-02-13T05:03:28Z
dc.identifier.issn0193-1857
dc.identifier.doi10.1152/ajpgi.00162.2010
dc.identifier.urihttp://hdl.handle.net/10072/42453
dc.description.abstractIt has been reported that the adjuvant-induced inflammation could affect drug metabolism in liver. Here we further investigated the effect of inflammation on drug transport in liver using taurocholate as a model drug. The hepatic disposition kinetics of [3H]taurocholate in perfused normal and adjuvant-treated rat livers were investigated by the multiple indicator dilution technique and data were analyzed by a previously reported hepatobiliary taurocholate transport model. Real-time RT-PCR was also performed to determine the mRNA expression of liver bile salt transporters in normal and diseased livers. The uptake and biliary excretion of taurocholate were impaired in the adjuvant-treated rats as shown by decreased influx rate constant kin (0.65 ᠰ.09 vs. 2.12 ᠰ.30) and elimination rate constant kbe (0.09 ᠰ.02 vs. 0.17 ᠰ.04) compared with control rat group, whereas the efflux rate constant kout was greatly increased (0.07 ᠰ.02 vs. 0.02 ᠰ.01). The changes of mRNA expression of liver bile salt transporters were found in adjuvant-treated rats. Hepatic taurocholate extraction ratio in adjuvant-treated rats (0.86 ᠰ.05, n = 6) was significantly reduced compared with 0.93 ᠰ.05 (n = 6) in normal rats. Hepatic extraction was well correlated with altered hepatic ATP content (r2 = 0.90). In conclusion, systemic inflammation greatly affects hepatic ATP content/production and associated transporter activities and causes an impairment of transporter-mediated solute trafficking and pharmacokinetics.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Physiological Society
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefromG130
dc.relation.ispartofpagetoG136
dc.relation.ispartofissue1
dc.relation.ispartofjournalAmerican Journal of Physiology: Gastrointestinal and Liver Physiology
dc.relation.ispartofvolume300
dc.rights.retentionY
dc.subject.fieldofresearchZoology
dc.subject.fieldofresearchMedical physiology
dc.subject.fieldofresearchcode3109
dc.subject.fieldofresearchcode3208
dc.titleEffect of adjuvant-induced systemic inflammation in rats on hepatic disposition kinetics of taurocholate
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.rights.copyrightSelf-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the author[s] for more information.
gro.date.issued2011
gro.hasfulltextNo Full Text
gro.griffith.authorWhitehouse, Michael


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