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Am J Physiol Gastrointest Liver Physiol (June 4, 2009). doi:10.1152/ajpgi.90728.2008
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Submitted on December 29, 2008
Revised on May 20, 2009
Accepted on May 29, 2009

Role of hepatic transporters in prevention of bile-acid toxicity after partial hepatectomy in mice

Iván L. Csanaky1, Lauren M. Aleksunes1, Yuji Tanaka2, and Curtis D. Klaassen1*

1 University of Kansas Medical Center
2 Univeresity of Kansas Medical Center

* To whom correspondence should be addressed. E-mail: cklaasse{at}kumc.edu.

The enterohepatic recirculation of bile acids (BA) is important in several physiological processes. Although there has been considerable research on liver regeneration after 2/3 partial hepatectomy (PHx), little is known about how the liver protects itself against BA toxicity during regeneration. In this study, various BAs in plasma and liver, the composition of micelle-forming bile constituents, as well as gene expression of the main hepatobiliary transporters were quantified in sham and PHx mice 24- and 48-hrs after surgery. PHx did not influence the hepatic concentrations of taurine-conjugated BAs (T-BA) but increased the concentration of glycine-conjugated (G-BA) and unconjugated BAs. Total BA excretion (ng/min/g liver weight) increased 2.4-fold and was accompanied by a 55% increase in bile flow after PHx. The plasma concentrations of T-BAs (402-fold), G-BAs (17-fold), and unconjugated- (500-fold) BAs increased. The mRNA and protein levels of the bile-acid uptake transporter Ntcp were unchanged after PHx, whereas the canalicular Bsep protein increased 2-fold at 48h. The basolateral efflux transporter Mrp3 was induced at the mRNA (2.6-fold) and protein (3.1-fold) levels after PHx, which may contribute to elevated plasma bile acid and bilirubin levels. Biliary phospholipid excretion was nearly doubled in PHx mice, most likely due to increased mRNA expression of the phospholipid transporter, Mdr2. In conclusion, the remnant liver after PHx excretes 2.5-fold more BAs and 3-times more phospholipids per gram liver than the sham operated mouse liver. Upregulation of phospholipid transport may be important in protecting the biliary tract from BA toxicity during PHx.







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