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Co-administration of ursodeoxycholic acid with rosuvastatin/ezetimibe in a non-alcoholic fatty liver disease model
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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9379373/ https://www.ncbi.nlm.nih.gov/pubmed/35982712 http://dx.doi.org/10.1093/gastro/goac037 |
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author | 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 |
author_facet | 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 |
author_sort | Seo, Sang Hyun |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9379373 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-93793732022-08-17 Co-administration of ursodeoxycholic acid with rosuvastatin/ezetimibe in a non-alcoholic fatty liver disease model 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 Gastroenterol Rep (Oxf) Original Article 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. Oxford University Press 2022-08-13 /pmc/articles/PMC9379373/ /pubmed/35982712 http://dx.doi.org/10.1093/gastro/goac037 Text en © The Author(s) 2022. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article 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 Co-administration of ursodeoxycholic acid with rosuvastatin/ezetimibe in a non-alcoholic fatty liver disease model |
title | Co-administration of ursodeoxycholic acid with rosuvastatin/ezetimibe in a non-alcoholic fatty liver disease model |
title_full | Co-administration of ursodeoxycholic acid with rosuvastatin/ezetimibe in a non-alcoholic fatty liver disease model |
title_fullStr | Co-administration of ursodeoxycholic acid with rosuvastatin/ezetimibe in a non-alcoholic fatty liver disease model |
title_full_unstemmed | Co-administration of ursodeoxycholic acid with rosuvastatin/ezetimibe in a non-alcoholic fatty liver disease model |
title_short | Co-administration of ursodeoxycholic acid with rosuvastatin/ezetimibe in a non-alcoholic fatty liver disease model |
title_sort | co-administration of ursodeoxycholic acid with rosuvastatin/ezetimibe in a non-alcoholic fatty liver disease model |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9379373/ https://www.ncbi.nlm.nih.gov/pubmed/35982712 http://dx.doi.org/10.1093/gastro/goac037 |
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