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Digestive Diseases and Sciences
Erschienen in: Digestive Diseases and Sciences 1/2016

01.01.2016 | Original Article

Rifampicin Induces Bicarbonate-Rich Choleresis in Rats: Involvement of Anion Exchanger 2

verfasst von: Wei Wang, Xiaofei Ren, Yi Cai, Lihong Chen, Weiping Zhang, Jianming Xu

Erschienen in: Digestive Diseases and Sciences | Ausgabe 1/2016

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Abstract

Background and Aim

Previous studies have shown that rifampicin induced choleresis, the mechanisms of which have not been described. The aim of this study was to investigate the mechanisms underlying in vivo rifampicin-induced choleresis.

Methods

In one experimental set, rats were treated chronically with rifampicin on days 1, 3 and 7. Serum and biliary parameters were assayed, and mRNA and protein levels, as well as the locations of the hepatic export transporters were analyzed by real-time PCR, western blot and immunofluorescence. Ductular mass was evaluated immunohistochemically. In another experimental set, rats received an acute infusion of rifampicin. The amount of rifampicin in bile was detected using HPLC. Biliary parameters were monitored following intrabiliary retrograde fluxes of the Cl−/HCO3 − exchange inhibitor 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS) or 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) in the infused rats.

Results

Biliary bicarbonate output increased in parallel to the augmented bile flow in response to rifampicin, and this effect was abolished with intrabiliary administration of DIDS, but not NPPB. The biliary secretion of rifampicin with increases in bile flow and biliary rifampicin in response to different infused doses of the antibiotic show no significant correlations. After rifampicin treatment, the expression level of anion exchanger 2 (AE2) increased, while the location of hepatic transporters did not change. However, RIF treatment did not increase ductular mass significantly.

Conclusions

These results indicate that the increase in bile flow induced by rifampicin is mainly due to increased HCO3 − excretion mediated by increased AE2 protein expression and activity.
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Literatur
1.
Veggi LM, Crocenzi FA, Roma MG, Mottino AD. Dapsone impairs the bile salt-independent fraction of bile flow in rats: possible involvement of its N-hydroxylated metabolite. Toxicology. 2005;211:97–106.CrossRefPubMed
2.
Matsumoto K, Imasato M, Yamazaki Y, et al. Claudin 2 deficiency reduces bile flow and increases susceptibility to cholesterol gallstone disease in mice. Gastroenterology. 2014;147:1134–1145.CrossRefPubMed
3.
Gerloff T, Stieger B, Hagenbuch B, et al. The sister of P-glycoprotein represents the canalicular bile salt export pump of mammalian liver. J Biol Chem. 1998;273:10046–10050.CrossRefPubMed
4.
Paulusma CC, van Geer MA, Evers R, et al. Canalicular multispecific organic anion transporter/multidrug resistance protein 2 mediates low-affinity transport of reduced glutathione. Biochem J. 1999;338:393–401.CrossRefPubMedPubMedCentral
5.
Meier PJ, Knickelbein R, Moseley RH, Dobbins JW, Boyer JL. Evidence for carrier-mediated chloride/bicarbonate exchange in canalicular rat liver plasma membrane vesicles. J Clin Invest. 1985;75:1256–1263.CrossRefPubMedPubMedCentral
6.
Tabibian JH, Masyuk AI, O’hara SP, Larusso NF, Masyuk TV. Physiology of cholangiocytes. Compr Physiol. 2013;3:541–565.PubMed
7.
Halilbasic E, Claudel T, Trauner M. Bile acid transporters and regulatory nuclear receptors in the liver and beyond. J Hepatol. 2013;58:155–168.CrossRefPubMedPubMedCentral
8.
González R, Cruz A, Ferrín G, et al. Cytoprotective properties of rifampicin are related to the regulation of detoxification system and bile acid transporter expression during hepatocellular injury induced by hydrophobic bile acids. J Hepatobiliary Pancreat Sci. 2011;18:740–750.CrossRefPubMed
9.
Mita S, Suzuki H, Akita H, et al. Inhibition of bile acid transport across Na+/taurocholate cotransporting polypeptide (SLC10A1) and bile salt export pump (ABCB 11)-coexpressing LLC-PK1 cells by cholestasis-inducing drugs. Drug Metab Dispos. 2006;34:1575–1581.CrossRefPubMed
10.
Byrne JA, Strautnieks SS, Mieli-vergani G, Higgins CF, Linton KJ, Thompson RJ. The human bile salt export pump: characterization of substrate specificity and identification of inhibitors. Gastroenterology. 2002;123:1649–1658.CrossRefPubMed
11.
Stieger B, Fattinger K, Madon J, Kullak-ublick GA, Meier PJ. Drug- and estrogen-induced cholestasis through inhibition of the hepatocellular bile salt export pump (Bsep) of rat liver. Gastroenterology. 2000;118:422–430.CrossRefPubMed
12.
Marschall HU, Wagner M, Zollner G, et al. Complementary stimulation of hepatobiliary transport and detoxification systems by rifampicin and ursodeoxycholic acid in humans. Gastroenterology. 2005;129:476–485.CrossRefPubMed
13.
Back DJ, Cross KJ, Hiley CR, Yates MS. The effect of rifampicin on liver blood flow, microsomal enzyme activity and bile flow in the rat. Biochem Pharmacol. 1979;28:1293–1296.CrossRefPubMed
14.
Oliven A, Bassan HM. Effects of rifampin and isoniazid on the isolated perfused rat liver. Chemotherapy. 1986;32:159–165.CrossRefPubMed
15.
Banales JM, Arenas F, Rodriguez-ortigosa CM, et al. Bicarbonate-rich choleresis induced by secretin in normal rat is taurocholate-dependent and involves AE2 anion exchanger. Hepatology. 2006;43:266–275.CrossRefPubMed
16.
Fickert P, Pollheimer MJ, Silbert D, et al. Differential effects of norUDCA and UDCA in obstructive cholestasis in mice. J Hepatol. 2013;58:1201–1208.CrossRefPubMedPubMedCentral
17.
Miura T, Kimura N, Yamada T, et al. Sustained repression and translocation of Ntcp and expression of Mrp4 for cholestasis after rat 90 % partial hepatectomy. J Hepatol. 2011;55:407–414.CrossRefPubMed
18.
Soroka CJ, Lee JM, Azzaroli F, Boyer JL. Cellular localization and up-regulation of multidrug resistance-associated protein 3 in hepatocytes and cholangiocytes during obstructive cholestasis in rat liver. Hepatology. 2001;33:783–791.CrossRefPubMed
19.
Wagner M, Halilbasic E, Marschall HU, et al. CAR and PXR agonists stimulate hepatic bile acid and bilirubin detoxification and elimination pathways in mice. Hepatology. 2005;42:420–430.CrossRefPubMed
20.
Staudinger JL, Goodwin B, Jones SA, et al. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. PNAS. 2001;98:3369–3374.CrossRefPubMedPubMedCentral
21.
He M, Zhang S, Jiao Y, et al. Effects and mechanisms of rifampin on hepatotoxicity of acetaminophen in mice. Food Chem Toxicol. 2012;50:3142–3149.CrossRefPubMed
22.
Hosagrahara V, Reddy J, Ganguly S, et al. Effect of repeated dosing on rifampin exposure in BALB/c mice. Eur J Pharm Sci. 2013;49:33–38.CrossRefPubMed
23.
Gonzalez P, Mauriz JL, Jimenez R, Gonzalez-gallego J, Tunon MJ. Choleresis and inhibition of biliary lipid secretion induced by piperacillin in the rat. Clin Exp Pharmacol Physiol. 2002;29:880–884.CrossRefPubMed
24.
Martinez-anso E, Castillo JE, Diez J, Medina JF, Prieto J. Immunohistochemical detection of chloride/bicarbonate anion exchangers in human liver. Hepatology. 1994;19:1400–1406.CrossRefPubMed
25.
26.
27.
28.
Turi JL, Jaspers I, Dailey LA, et al. Oxidative stress activates anion exchange protein 2 and AP-1 in airway epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2002;283:L791–L798.CrossRefPubMed
29.
Zhou C, Tiberi M, Liang B, Alper SL, Baltz JM. HCO3 −/Cl− exchange inactivation and reactivation during mouse oocyte meiosis correlates with MEK/MAPK-regulated Ae2 plasma membrane localization. PLoS One. 2009;4:e7417.CrossRefPubMedPubMedCentral
30.
Medina JF, Martinez-anso E, Vazquez JJ, Prieto J. Decreased anion exchanger 2 immunoreactivity in the liver of patients with primary biliary cirrhosis. Hepatology. 1997;25:12–17.CrossRefPubMed
31.
Prieto J, Qian C, Garcia N, Diez J, Medina JF. Abnormal expression of anion exchanger genes in primary biliary cirrhosis. Gastroenterology. 1993;105:572–578.PubMed
32.
Banales JM, Saez E, Uriz M, et al. Up-regulation of microRNA 506 leads to decreased Cl-/HCO3- anion exchanger 2 expression in biliary epithelium of patients with primary biliary cirrhosis. Hepatology. 2012;56:687–697.CrossRefPubMedPubMedCentral
33.
Salas JT, Banales JM, Sarvide S, et al. Ae2a, b-deficient mice develop antimitochondrial antibodies and other features resembling primary biliary cirrhosis. Gastroenterology. 2008;134:1482–1493.CrossRefPubMed
34.
Hoensch HP, Balzer K, Dylewizc P, Kirch W, Goebell H, Ohnhaus EE. Effect of rifampicin treatment on hepatic drug metabolism and serum bile acids in patients with primary biliary cirrhosis. Eur J Clin Pharmacol. 1985;28:475–477.CrossRefPubMed
35.
Podesta A, Lopez P, Terg R, et al. Treatment of pruritus of primary biliary cirrhosis with rifampin. Dig Dis Sci. 1991;36:216–220.CrossRefPubMed
36.
Bachs L, Pares A, Elena M, Piera C, Rodes J. Effects of long-term rifampicin administration in primary biliary cirrhosis. Gastroenterology. 1992;102:2077–2080.PubMed
37.
Ghent CN, Carruthers SG. Treatment of pruritus in primary biliary cirrhosis with rifampin. Results of a double-blind, crossover, randomized trial. Gastroenterology. 1988;94:488–493.PubMed
38.
Bachs L, Pares A, Elena M, Piera C, Rodes J. Comparison of rifampicin with phenobarbitone for treatment of pruritus in biliary cirrhosis. Lancet. 1989;1:574–576.CrossRefPubMed
39.
Cancado EL, Leitao RM, Carrilho FJ, Laudanna AA. Unexpected clinical remission of cholestasis after rifampicin therapy in patients with normal or slightly increased levels of gamma-glutamyl transpeptidase. Am J Gastroenterol. 1998;93:1510–1517.PubMed
40.
Hohenester S, Wenniger LM, Paulusma CC, et al. A biliary HCO3-umbrella constitutes a protective mechanism against bile acid-induced injury in human cholangiocytes. Hepatology. 2012;55:173–183.CrossRefPubMed
Metadaten
Titel
Rifampicin Induces Bicarbonate-Rich Choleresis in Rats: Involvement of Anion Exchanger 2
verfasst von
Wei Wang
Xiaofei Ren
Yi Cai
Lihong Chen
Weiping Zhang
Jianming Xu
Publikationsdatum
01.01.2016
Verlag
Springer US
Erschienen in
Digestive Diseases and Sciences / Ausgabe 1/2016
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-015-3850-2

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