Effect of adjuvant-induced systemic inflammation in rats on hepatic disposition kinetics of taurocholate

Roberts, Michael S., Liu, Xin, Zou, Yuhong, Siebert, Gerhard A., Chang, Ping, Whitehouse, Michael W., Fletcher, Linda and Crawford, Darrell H. G. (2011) Effect of adjuvant-induced systemic inflammation in rats on hepatic disposition kinetics of taurocholate. American Journal of Physiology-gastrointestinal And Liver Physiology, 300 1: G130-G136. doi:10.1152/ajpgi.00162.2010

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Author Roberts, Michael S.
Liu, Xin
Zou, Yuhong
Siebert, Gerhard A.
Chang, Ping
Whitehouse, Michael W.
Fletcher, Linda
Crawford, Darrell H. G.
Title Effect of adjuvant-induced systemic inflammation in rats on hepatic disposition kinetics of taurocholate
Journal name American Journal of Physiology-gastrointestinal And Liver Physiology   Check publisher's open access policy
ISSN 0193-1857
Publication date 2011-01-01
Year available 2010
Sub-type Article (original research)
DOI 10.1152/ajpgi.00162.2010
Open Access Status
Volume 300
Issue 1
Start page G130
End page G136
Total pages 7
Place of publication Bethesda, MD, U.S.A.
Publisher American Physiological Society
Language eng
Abstract It 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 ± 0.09 vs. 2.12 ± 0.30) and elimination rate constant kbe (0.09 ± 0.02 vs. 0.17 ± 0.04) compared with control rat group, whereas the efflux rate constant kout was greatly increased (0.07 ± 0.02 vs. 0.02 ± 0.01). 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 ± 0.05, n = 6) was significantly reduced compared with 0.93 ± 0.05 (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. Copyright © 2011 the American Physiological Society
Keyword Hepatic extraction
Bile salt transporter
Systemic inflammation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online before print October 2010.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Medicine Publications
 
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Created: Tue, 22 Mar 2011, 19:18:43 EST by Dr Xin Liu on behalf of Medicine - Princess Alexandra Hospital