Co-administration of ursodeoxycholic acid with rosuvastatin/ezetimibe in a non-alcoholic fatty liver disease model. (13th August 2022)

• Record Type: Journal Article
• Authors: Seo, Sang Hyun; Lee, Da Hyun; Lee, Yu Seol; Cho, Kyung Joo; Park, Hye Jung; Lee, Hye Won; Kim, Beom Kyung; Park, Jun Yong; Kim, Do Young; Ahn, Sang Hoon; Bae, Soo Han; Kim, Seung Up
• Is Part Of: Gastroenterology report. Volume 10(2022)
• Publication Date: 2022-08-13
• Subjects: non-alcoholic fatty liver disease -- non-alcoholic steatohepatitis -- ursodeoxycholic acid -- rosuvastatin -- ezetimibe; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1093/gastro/goac037
• Languages: English
• ISSNs: 2052-0034

Abstract

Abstract: 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.