The ameliorative effect of niclosamide on bile duct ligation induced liver fibrosis via suppression of NOTCH and Wnt pathways
Esmail, Manar M; Saeed, Noha M; Effat, Haidy; El-Naga RN;
Abstract
Liver fibrosis is the conjoint consequence of almost all chronic liver diseases. Cholestatic liver injury is a significant stimulus for fibrotic liver. This study was conducted to investigate the hepatoprotective effect of niclosamide as a NOTCH inhibitor and on the Wnt pathway against cholestatic liver fibrosis (CLF) which was experimentally induced by bile duct ligation (BDL). Rats were randomly divided into five main groups (6 per group): sham, BDL, BDL/niclosamide 5, BDL/niclosamide 10 and niclosamide 10 only group. Niclosamide was administered intraperitoneally (i.p.) for 4 weeks starting at the same day of surgery at doses 5 and 10 mg/kg. Liver function, cholestasis, oxidative stress, inflammation, liver fibrosis, NOTCH signaling pathway and Wnt pathway markers were assessed. Niclosamide (5 and 10 mg/kg) significantly reduced liver enzymes levels, oxidative stress, inflammation and phosphorylated signal transducer and activator of transcription3 (p-STAT3). Niclosamide (5 and 10 mg/kg) also significantly reduced NOTCH pathway (Jagged1, NOTCH2, NOTCH3, HES1, SOX9), Wnt pathway (Wnt5B, and Wnt10A), and fibrosis (transforming growth factor-beta1 (TGF-β1), alpha smooth muscle actin (α-SMA) and collagen deposition with more prominent effect of the higher dose 10 mg/kg. So, this study presents nicloamide as a promising antifibrotic agent in CLF through inhibition of NOTCH and Wnt pathways.
Other data
Title | The ameliorative effect of niclosamide on bile duct ligation induced liver fibrosis via suppression of NOTCH and Wnt pathways | Authors | Esmail, Manar M; Saeed, Noha M; Effat, Haidy ; El-Naga RN | Keywords | Bile duct ligation;Cholestatic liver fibrosis;NOTCH;Niclosamide;Wnt | Issue Date | 4-May-2021 | Publisher | ELSEVIER IRELAND LTD | Journal | Toxicology letters | Volume | 347 | Start page | 23 | End page | 35 | ISSN | 03784274 | DOI | 10.1016/j.toxlet.2021.04.018 | PubMed ID | 33961984 | Scopus ID | 2-s2.0-85105480752 | Web of science ID | WOS:000656465800003 |
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