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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
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.
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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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