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Co-administration of ursodeoxycholic acid with rosuvastatin/ezetimibe in a non-alcoholic fatty liver disease model

 Sang Hyun Seo  ;  Da Hyun Lee  ;  Yu Seol Lee  ;  Kyung Joo Cho  ;  Hye Jung Park  ;  Hye Won Lee  ;  Beom Kyung Kim  ;  Jun Yong Park  ;  Do Young Kim  ;  Sang Hoon Ahn  ;  Soo Han Bae  ;  Seung Up Kim 
 GASTROENTEROLOGY REPORT, Vol.10 : goac037, 2022-08 
Journal Title
Issue Date
ezetimibe ; non-alcoholic fatty liver disease ; non-alcoholic steatohepatitis ; rosuvastatin ; ursodeoxycholic acid
Background: Ursodeoxycholic acid (UDCA), statins, and ezetimibe (EZE) have demonstrated beneficial effects against non-alcoholic fatty liver disease (NAFLD). We investigated the efficacy of the combination of UDCA and the mix of rosuvastatin (RSV)/EZE in the treatment of NAFLD.

Methods: NAFLD mouse models were developed by injecting thioacetamide, fasting, and high-carbohydrate refeeding, high-fat diet, and choline-deficient L-amino acid-defined high-fat diet (CDAHFD). Low-dose UDCA (L-UDCA; 15 mg/kg) or high-dose UDCA (H-UDCA; 30 mg/kg) was administered with RSV/EZE. We also employed an in vitro model of NAFLD developed using palmitic acid-treated Hepa1c1c7 cells.

Results: Co-administration of RSV/EZE with UDCA significantly decreased the collagen accumulation, serum alanine aminotransferase (ALT) levels, and mRNA levels of fibrosis-related markers than those observed in the vehicle group in thioacetamide-treated mice (all P < 0.01). In addition, in the group fasted and refed with a high-carbohydrate diet, UDCA/RSV/EZE treatment decreased the number of apoptotic cells and serum ALT levels compared with those observed in the vehicle group (all P < 0.05). Subsequently, H-UDCA/RSV/EZE treatment decreased the number of ballooned hepatocytes and stearoyl-CoA desaturase 1 (SCD-1) mRNA levels (P = 0.027) in the liver of high-fat diet-fed mice compared with those observed in the vehicle group. In the CDAHFD-fed mouse model, UDCA/RSV/EZE significantly attenuated collagen accumulation and fibrosis-related markers compared to those observed in the vehicle group (all P < 0.05). In addition, UDCA/RSV/EZE treatment significantly restored cell survival and decreased the protein levels of apoptosis-related markers compared to RSV/EZE treatment in palmitic acid-treated Hepa1c1c7 cells (all P < 0.05).

Conclusion: Combination therapy involving UDCA and RSV/EZE may be a novel strategy for potent inhibition of NAFLD progression.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Do Young(김도영)
Kim, Beom Kyung(김범경) ORCID logo https://orcid.org/0000-0002-5363-2496
Kim, Seung Up(김승업) ORCID logo https://orcid.org/0000-0002-9658-8050
Park, Jun Yong(박준용) ORCID logo https://orcid.org/0000-0001-6324-2224
Bae, Soo Han(배수한) ORCID logo https://orcid.org/0000-0002-8007-2906
Ahn, Sang Hoon(안상훈) ORCID logo https://orcid.org/0000-0002-3629-4624
Lee, Da Hyun(이다현) ORCID logo https://orcid.org/0000-0002-5412-6878
Lee, Hye Won(이혜원) ORCID logo https://orcid.org/0000-0002-3552-3560
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