Clinical—liver, pancreas, and biliary tractComplementary Stimulation of Hepatobiliary Transport and Detoxification Systems by Rifampicin and Ursodeoxycholic Acid in Humans
Section snippets
Patients
Otherwise healthy patients scheduled for laparascopic cholestectomy for symptomatic gallstone disease were invited to participate in a clinical study of the metabolic and molecular effects of UDCA and RIFA. This approach was taken because such a detailed analysis of liver, bile, serum, and urine is not feasible in patients not scheduled for a surgical abdominal procedure. Potential candidates completed a clinical research file consisting of a detailed questionnaire about the patient’s history
Patients’ Demographics, Routine Biochemistry and Type of Gallstones
The patients randomized to control, RIFA, or UDCA groups did not differ significantly in mean age (range, 29–77 years of age) or body mass index (range, 24.4–35.9 kg/m2). Females outnumbered males (in line with the target population in cholestatic liver diseases such as PBC), and there were more women in the UDCA group (n = 9) than in the RIFA (n = 6) or control (n = 7) groups (Table 1). All patients had cholesterol gallstones.
No adverse effects from study medications were reported. Serum
Discussion
The present study was performed to define the molecular mechanisms of action of 2 drugs—RIFA5, 7, 8 and UDCA (recently reviewed by Paumgartner and Beuers1)—that were shown to improve serum liver biochemistry and symptoms in patients with cholestatic liver diseases such as primary biliary cirrhosis (PBC). We found that RIFA and UDCA both enhance expression of distinct but complementary sets of bile acid/bilirubin metabolizing/detoxifying enzymes and their corresponding hepatobiliary ABC
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2022, Molecular and Cellular EndocrinologyCitation Excerpt :Why then is UDCA beneficial in chronic cholestatic liver disease despite being FXR antagonistic? Several modes of action in combination may explain this and should be listed here (Beuers, 2006): rendering a hydrophobic biliary bile acid pool into a more hydrophilic and less toxic one; stimulation of bile-acid dependent and independent bile flow; increasing biliary protection by a bicarbonate umbrella (Beuers et al., 2012), anti-apoptotic effects; autophagy stimulating effects (Panzitt et al., 2020); induction of the alternative bile acid export pump MRP4 (Marschall et al., 2005; Renga et al., 2011) and induction of canalicular BSEP (Marschall et al., 2005). Similar to the FXR agonistic glycine-UDCA, which is a low abundant natural bile acid in human, the murine primary bile acids tauro-αMCA and tauro-βMCA are FXR antagonists (Sayin et al., 2013) (Fig. 3).
Supported by grants from Karolinska Institutet, Ruth och Richard Julins Fond, and the Swedish Medical Association (to H.U.M.) and by grant 10266 from the Austrian National Bank and P15502 from the Austrian Science Foundation (to M.T.).