مورد إلكتروني
Unaltered liver regeneration in post‐cholestatic rats treated with the fxr agonist obeticholic acid
| العنوان: | Unaltered liver regeneration in post‐cholestatic rats treated with the fxr agonist obeticholic acid |
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| بيانات النشر: | 2021-02-01 |
| تفاصيل مُضافة: | de Haan, L.R. (Lianne R.) Verheij, J. (Joanne) Golen, R.F. (Rowan) van Horneffer‐van der Sluis, V. (Verena) Lewis, M.R. (Matthew R.) Beuers, U. (Ulrich) Gulik, T.M. (Thomas) van Olde Damink, S.W.M. (Steven) Schaap, F.G. (Frank) Heger, M. (Michal) Olthof, P.B. (Pim B.) |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | In a previous study, obeticholic acid (OCA) increased liver growth before partial hepatectomy (PHx) in rats through the bile acid receptor farnesoid X‐receptor (FXR). In that model, OCA was administered during obstructive cholestasis. However, patients normally undergo PHx several days after biliary drainage. The effects of OCA on liver regeneration were therefore studied in post‐cholestatic Wistar rats. Rats underwent sham surgery or reversible bile duct ligation (rBDL), which was relieved after 7 days. PHx was performed one day after restoration of bile flow. Rats received 10 mg/kg OCA per day or were fed vehicle from restoration of bile flow until sacrifice 5 days after PHx. Liver regeneration was comparable between cholestatic and non‐cholestatic livers in PHx‐subjected rats, which paralleled liver regeneration a human validation cohort. OCA treatment induced ileal Fgf15 mRNA expression but did not enhance post‐PHx hepatocyte proliferation through FXR/SHP signaling. OCA treatment neither increased mitosis rates nor recovery of liver weight after PHx but accelerated liver regrowth in rats that had not been subjected to rBDL. OCA did not increase biliary injury. Conclusively, OCA does not induce liver regeneration in post‐cholestatic rats and does not exacerbate biliary damage that results from cholestasis. This study challenges the previously reported beneficial effects of OCA in liv |
| مصطلحات الفهرس: | Basolateral and canalicular transporters, Bile acid metabolism, Bile duct obstruction, Bile salts, Biliary obstruction, Liver regeneration, Partial hepatectomy, Pharmacological intervention, info:eu-repo/semantics/article |
| DOI: | 10.3390.biom11020260 |
| URL: | |
| الإتاحة: | Open access content. Open access content info:eu-repo/semantics/openAccess |
| ملاحظة: | Biomolecules vol. 11 no. 2, pp. 1-22 English |
| أرقام أخرى: | QGQ oai:repub.eur.nl:134772 doi:10.3390/biom11020260 urn:hdl:1765/134772 1244878957 |
| المصدر المساهم: | ERASMUS UNIVERSITEIT ROTTERDAM From OAIster®, provided by the OCLC Cooperative. |
| رقم الأكسشن: | edsoai.on1244878957 |
| قاعدة البيانات: | OAIster |
| DOI: | 10.3390.biom11020260 |
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