1. Volume 129, Issue 2, Pages 476-485 (August 2005)
Complementary Stimulation of Hepatobiliary Transport and Detoxification Systems by Rifampicin and Ursodeoxycholic Acid in Humans 
Hanns—Ulrich Marschall, Martin Wagner, Gernot Zollner, Peter Fickert, Ulf Diczfalusy, Judith Gumhold, Dagmar Silbert, Andrea Fuchsbichler, Lisbet Benthin, Rosita Grundström, Ulf Gustafsson, Staffan Sahlin, Curt Einarsson, Michael Trauner 
Gastroenterology 
Volume 129, Issue 2, Pages (August 2005)
DOI: /j.gastro
Copyright © 2005 American Gastroenterological Association Terms and Conditions

2. Figure 1
Effects of RIFA and UDCA on cytochrome P450 (A) and bile acid synthesis (B). The serum marker of CYP3A4 induction 4β-hydroxycholesterol increased in each patient treated with RIFA or UDCA (A). The serum marker for endogenous bile acid synthesis 7α-hydroxy-4-cholestene-3-one increased significantly only in the group of patients treated with RIFA (B). P < .05: significantly different compared with baseline. RIFA, solid line; UDCA, broken line.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2005 American Gastroenterological Association Terms and Conditions

3. Figure 2
Effects of RIFA and UDCA on bile acids in serum (A) and gallbladder (B) bile. Serum (A) and biliary (B) bile acid concentrations at the end of treatment with RIFA or UDCA, compared with controls. For easier comparison, baseline serum data that did not differ between groups are not shown. LCA, lithocholic acid; DCA, deoxycholic acid; CDCA, chenodeoxycholic acid; CA, cholic acid; UDCA, ursodeoxycholic acids. P < .05: significantly different compared with controls.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2005 American Gastroenterological Association Terms and Conditions

4. Figure 3
Effects of RIFA and UDCA on hepatic mRNA expression of nuclear receptors and hepatobiliary transport systems (A) and bilirubin and bile acid metabolizing enzymes (B). Total RNA was isolated from liver biopsy specimens of patients randomized to control, RIFA, or UDCA and analyzed by real-time PCR as described in the Materials and Methods section. Data are expressed as percentage ± SD. P < .05: significantly different compared with controls.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2005 American Gastroenterological Association Terms and Conditions

5. Figure 4
Effects of RIFA on hepatic protein expression of hepatobiliary transport proteins. Proteins were isolated from controls, RIFA, or UDCA patients and analyzed by Western blotting as described in the Materials and Methods section. Protein expression levels calculated in relation to indicated (R) reference. P < .05: significantly different compared with controls.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2005 American Gastroenterological Association Terms and Conditions

6. Figure 5
Effects of UDCA on hepatic protein expression of hepatobiliary transport proteins. Proteins were isolated from controls, RIFA, or UDCA patients and analyzed by Western blotting as described in the Materials and Methods section. Protein expression levels calculated in relation to indicated (R) reference. P < .05: significantly different compared with controls.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2005 American Gastroenterological Association Terms and Conditions

7. Figure 6
BSEP, MDR3, and MRP2 immunofluorescence staining in liver biopsy specimens from control, RIFA, and UDCA patients. Immunofluorescence staining was performed with specific primary antibodies against BSEP, MDR3, and MRP2 as described in Zollner et al.26 Canalicular localization of these transporters is maintained under all conditions. Bar = 20 μm.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2005 American Gastroenterological Association Terms and Conditions

8. Figure 7
Schematic representation of observed effects of RIFA and UDCA on hepatobiliary transport systems and bile acid and bilirubin metabolizing enzymes. RIFA enhances excretion of bilirubin by (1) inducing the bilirubin glucuronyl transferase UGT1A1 and (2) inducing the bilirubin-glucuronide transport protein MDR2; RIFA as the prototype inducer of CYP3A4 facilitates conversion of hydrophobic bile acids (LCA, CDCA) into hydrophilic 6α-hydroxylated compounds that become glucuronidated and most likely are excreted via MRP3, the only transport system known so far to be intrinsically up-regulated in primary biliary cirrhosis. UDCA on the other hand induces protein expression of various transport systems including BSEP for the excretion of bile salts and MDR3 for the excretion of phospholipids, both at the canalicular pole, and MRP4 for the excretion of bile salts/organic anion conjugates at the basolateral side of the hepatocyte. These complementary effects may help to reduce cholestatic liver injury induced by bile acids and other potentially toxic biliary constituents.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2005 American Gastroenterological Association Terms and Conditions